diff --git a/src/components/DrugInteractionChecker.tsx b/src/components/DrugInteractionChecker.tsx new file mode 100644 index 0000000..f8d8b51 --- /dev/null +++ b/src/components/DrugInteractionChecker.tsx @@ -0,0 +1,793 @@ +/* eslint-disable no-underscore-dangle */ +import React, { useMemo, useState, createContext } from "react"; +import { + Typography, + Box, + ThemeProvider, + createTheme, + CssBaseline, + alpha, + Button, + useTheme, + InputBase, + Paper, + GlobalStyles, + Grid, + Card, + CardContent, + Link, + Zoom, + Fade, + Grow, + Tooltip, + IconButton, + Dialog, + DialogTitle, + DialogContent, + DialogActions, + Accordion, + AccordionSummary, + AccordionDetails, + Collapse, + AppBar, + Toolbar, + Container, + Menu, + MenuItem, + Drawer, + List, + ListItemButton, + ListItemText, + Divider, + ListSubheader +} from "@mui/material"; + +// Standard MUI Icons +import SearchIcon from "@mui/icons-material/Search"; +import RefreshIcon from "@mui/icons-material/Refresh"; +import ScienceIcon from "@mui/icons-material/Science"; +import WarningAmberIcon from '@mui/icons-material/WarningAmber'; +import CheckCircleOutlineIcon from '@mui/icons-material/CheckCircleOutline'; +import DangerousIcon from '@mui/icons-material/Dangerous'; +import ReportProblemIcon from '@mui/icons-material/ReportProblem'; +import OpenInNewIcon from '@mui/icons-material/OpenInNew'; +import LightModeIcon from "@mui/icons-material/LightMode"; +import DarkModeIcon from "@mui/icons-material/DarkMode"; +import CloseIcon from '@mui/icons-material/Close'; +import SwapHorizIcon from '@mui/icons-material/SwapHoriz'; +import ExpandMoreIcon from '@mui/icons-material/ExpandMore'; +import BiotechIcon from "@mui/icons-material/Biotech"; +import InfoOutlinedIcon from '@mui/icons-material/InfoOutlined'; +import MenuIcon from '@mui/icons-material/Menu'; +import KeyboardArrowDownIcon from '@mui/icons-material/KeyboardArrowDown'; +import ChevronRightIcon from '@mui/icons-material/ChevronRight'; + +// Import Data +import combosDataRaw from './combos.json'; + +// --- TYPES --- +interface Source { author?: string; title?: string; url?: string; } +interface Interaction { status: string; note?: string; sources?: Source[]; } +interface DrugData { [key: string]: { [key: string]: Interaction; }; } + +const combosData = combosDataRaw as DrugData; + +// --- DEFINITIONS --- +const RISK_DEFINITIONS = [ + { + label: "Low Risk & Synergy", + status: "Low Risk & Synergy", + desc: "These drugs work together to cause an effect greater than the sum of its parts, and they aren't likely to cause an adverse or undesirable reaction when used carefully. Additional research should always be done before combining drugs." + }, + { + label: "Low Risk & No Synergy", + status: "Low Risk & No Synergy", + desc: "Effects are additive. The combination is unlikely to cause any adverse or undesirable reaction beyond those that might ordinarily be expected from these drugs." + }, + { + label: "Low Risk & Decrease", + status: "Low Risk & Decrease", + desc: "Effects are subtractive. The combination is unlikely to cause any adverse or undesirable reaction beyond those that might ordinarily be expected from these drugs." + }, + { + label: "Caution", + status: "Caution", + desc: "These combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination." + }, + { + label: "Unsafe", + status: "Unsafe", + desc: "There is considerable risk of physical harm when taking these combinations, they should be avoided where possible." + }, + { + label: "Dangerous", + status: "Dangerous", + desc: "These combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death." + }, + { + label: "Unknown", + status: "Unknown", + desc: "Effects are unknown." + } +]; + +// --- THEME --- +const ColorModeContext = createContext({ toggleColorMode: () => {} }); + +const getAppleTheme = (mode: "light" | "dark") => + createTheme({ + palette: { + mode, + background: { + default: mode === "light" ? "#F5F5F7" : "#000000", + paper: mode === "light" ? "#FFFFFF" : "#1C1C1E", + }, + text: { + primary: mode === "light" ? "#1D1D1F" : "#F5F5F7", + secondary: mode === "light" ? "#86868B" : "#A1A1A6", + }, + primary: { main: mode === "light" ? "#0071E3" : "#2997FF" }, + divider: mode === "light" ? "rgba(0, 0, 0, 0.06)" : "rgba(255, 255, 255, 0.12)", + }, + typography: { + fontFamily: '-apple-system, BlinkMacSystemFont, "SF Pro Text", "SF Pro Display", "Segoe UI", Roboto, Helvetica, Arial, sans-serif', + h3: { fontWeight: 800, letterSpacing: "-0.02em" }, + h4: { fontWeight: 700, letterSpacing: "-0.01em" }, + body1: { fontSize: "1rem", lineHeight: 1.6 }, + button: { textTransform: "none", fontWeight: 600 }, + }, + shape: { borderRadius: 20 }, + components: { + MuiCssBaseline: { + styleOverrides: { + body: { backgroundColor: mode === "light" ? "#F5F5F7" : "#000000" }, + "*::-webkit-scrollbar": { width: "8px", height: "8px" }, + "*::-webkit-scrollbar-track": { background: "transparent" }, + "*::-webkit-scrollbar-thumb": { + backgroundColor: mode === "dark" ? "rgba(255,255,255,0.2)" : "rgba(0,0,0,0.1)", + borderRadius: "10px", + border: "2px solid transparent", + backgroundClip: "content-box", + }, + "*::-webkit-scrollbar-thumb:hover": { + backgroundColor: mode === "dark" ? "rgba(255,255,255,0.3)" : "rgba(0,0,0,0.2)", + }, + } + }, + MuiButton: { styleOverrides: { root: { borderRadius: 14, padding: "8px 16px", boxShadow: "none", "&:hover": { boxShadow: "none" } } } }, + MuiDialog: { + styleOverrides: { + paper: { + borderRadius: 24, + backgroundColor: mode === "light" ? "rgba(255, 255, 255, 0.85)" : "rgba(28, 28, 30, 0.85)", + backdropFilter: "blur(20px) saturate(180%)", + boxShadow: "0 25px 50px -12px rgba(0, 0, 0, 0.5)" + } + } + } + } + }); + +const MeshGradient = () => { + const theme = useTheme(); + const isDark = theme.palette.mode === 'dark'; + return ( + + ) +} + +// --- CLASSIC TRIPSIT HEADER COMPONENT --- +const TripSitHeader = ({ toggleColorMode, mode }: { toggleColorMode: () => void, mode: 'light' | 'dark' }) => { + const [anchorElResources, setAnchorElResources] = useState(null); + const [anchorElGuides, setAnchorElGuides] = useState(null); + const [mobileOpen, setMobileOpen] = useState(false); + + const handleOpenResources = (event: React.MouseEvent) => setAnchorElResources(event.currentTarget); + const handleCloseResources = () => setAnchorElResources(null); + + const handleOpenGuides = (event: React.MouseEvent) => setAnchorElGuides(event.currentTarget); + const handleCloseGuides = () => setAnchorElGuides(null); + + // Style mimicking the bootstrap header provided + const navLinkStyle = { + color: '#rgba(255,255,255,0.85)', + textDecoration: 'none', + fontWeight: 400, + fontSize: '1rem', + mx: 1.5, + cursor: 'pointer', + display: 'flex', + alignItems: 'center', + fontFamily: '-apple-system, BlinkMacSystemFont, "Segoe UI", Roboto, "Helvetica Neue", Arial, sans-serif', + '&:hover': { color: '#ffffff', opacity: 1 } + }; + + const logoUrl = "https://tripsit.me/wp-content/uploads/2018/08/tripsit-logo-v7.png"; + + return ( + + + + + {/* Logo */} + + + + + {/* Desktop Navigation */} + + Home + About + + {/* Resources Dropdown */} + + + Resources + + + Drug Info + Wiki + Factsheets + Comboapp + Printing Information + Drug User's Handbook + + + Calculators + DXM Dosage + Volumetric + Benzo Conversion + + + Test Kits + DanceSafe (Worldwide) + ProTest (Europe) + + + Learning Platform + Android App + Service Status + + + + {/* Guides Dropdown */} + + + Guides + + + Harm Reduction + Psychedelic Myths + Test Kits + + + TripSitting + Intro to TripSitting + TripSit in Real Life + Deal with a Bad Trip + + + Recovery + Stimulant Comedowns + Withdrawals + + + Dosing + Volumetric Dosing + + + + Volunteer + FAQ + Updates + Ban Appeal + + + {/* Action Buttons */} + + + + + {/* Subtle Theme Toggle */} + + + {mode === 'dark' ? : } + + + + + {/* Mobile Menu Icon */} + + + {mode === 'dark' ? : } + + setMobileOpen(true)} sx={{ color: '#fff' }}> + + + + + + + {/* Mobile Drawer */} + setMobileOpen(false)} + PaperProps={{ sx: { width: 300, bgcolor: '#212529', color: 'white' } }} + > + + setMobileOpen(false)} sx={{ color: 'white' }}> + + + + + setAnchorElResources(anchorElResources ? null : document.body)}> + + + + setAnchorElGuides(anchorElGuides ? null : document.body)}> + + + + + + + + + + + + + + ); +}; + +// --- RISK HELPERS --- +const RISK_COLORS: Record = { + "Low Risk": { dark: "#30D158", light: "#34C759", bgLight: "#E8FBEB", bgDark: "rgba(48, 209, 88, 0.15)", icon: CheckCircleOutlineIcon }, + "Caution": { dark: "#FFD60A", light: "#FFCC00", bgLight: "#FFFBE6", bgDark: "rgba(255, 214, 10, 0.15)", icon: WarningAmberIcon }, + "Unsafe": { dark: "#FF9F0A", light: "#FF9500", bgLight: "#FFF5E6", bgDark: "rgba(255, 159, 10, 0.15)", icon: ReportProblemIcon }, + "Dangerous": { dark: "#FF453A", light: "#FF3B30", bgLight: "#FFEBEA", bgDark: "rgba(255, 69, 58, 0.15)", icon: DangerousIcon }, + "Unknown": { dark: "#8E8E93", light: "#8E8E93", bgLight: "#F2F2F7", bgDark: "rgba(142, 142, 147, 0.15)", icon: ScienceIcon }, +}; + +const getRiskStyle = (status: string, isDark: boolean) => { + const key = Object.keys(RISK_COLORS).find(k => status.toLowerCase().includes(k.toLowerCase())) || "Unknown"; + return RISK_COLORS[key]; +} + +// --- RISK GUIDE MODAL --- +const RiskLegendModal = ({ open, onClose }: { open: boolean, onClose: () => void }) => { + const theme = useTheme(); + const isDark = theme.palette.mode === 'dark'; + + return ( + + + Risk Guide + + + + + {RISK_DEFINITIONS.map((def, idx) => { + const style = getRiskStyle(def.status, isDark); + const Icon = style.icon; + return ( + + + + + {def.label} + + {def.desc} + + + ) + })} + + + + + + + ); +}; + +// --- MAIN COMPONENTS --- + +const AnalyzerCard = ({ result, selectedDrugs, onReset }: { result: any, selectedDrugs: string[], onReset: () => void }) => { + const theme = useTheme(); + const isDark = theme.palette.mode === 'dark'; + + // Pulse Animation for the icon + const iconAnimation = { + '@keyframes pulse': { + '0%': { boxShadow: `0 0 0 0 ${alpha(theme.palette.background.paper, 0.7)}` }, + '70%': { boxShadow: `0 0 0 10px ${alpha(theme.palette.background.paper, 0)}` }, + '100%': { boxShadow: `0 0 0 0 ${alpha(theme.palette.background.paper, 0)}` }, + } + }; + + return ( + // "Suck Away" Animation: Collapse with a slower duration for drama + + {result && ( + + + + {(() => { + const style = getRiskStyle(result.status, isDark); + const Icon = style.icon; + return ( + + {/* Animated Icon */} + + + + + + {result.status} + + + {/* Centered Bubble */} + + + {selectedDrugs[0]} + + + + {selectedDrugs[1]} + + + + ); + })()} + + + + {result.note || "No specific note available."} + + + + {/* Sources Dropdown */} + {result.sources && result.sources.length > 0 && ( + + } sx={{ p: 0, minHeight: 0 }}> + + Sources ({result.sources.length}) + + + + + {result.sources.map((s: Source, i: number) => ( + + + {s.title || "Reference Link"} + + ))} + + + + )} + + + + + + )} + + ); +}; + +const InteractionChecker = () => { + const theme = useTheme(); + const isDark = theme.palette.mode === 'dark'; + const [selectedDrugs, setSelectedDrugs] = useState([]); + const [searchTerm, setSearchTerm] = useState(''); + const [legendOpen, setLegendOpen] = useState(false); + + const allDrugs = useMemo(() => Object.keys(combosData).sort(), []); + const filteredDrugs = useMemo(() => { + if (!searchTerm) return allDrugs; + return allDrugs.filter(d => d.toLowerCase().includes(searchTerm.toLowerCase())); + }, [allDrugs, searchTerm]); + + const handleDrugClick = (drug: string) => { + if (selectedDrugs.includes(drug)) { + setSelectedDrugs(prev => prev.filter(d => d !== drug)); + } else { + if (selectedDrugs.length < 2) { + setSelectedDrugs(prev => [...prev, drug]); + } else { + setSelectedDrugs(prev => [prev[0], drug]); + } + } + }; + + const result = useMemo(() => { + if (selectedDrugs.length !== 2) return null; + const [a, b] = selectedDrugs; + let interaction = combosData[a]?.[b]; + if (!interaction) interaction = combosData[b]?.[a]; + if (!interaction) return { status: "Unknown", note: "No specific data found." }; + return interaction; + }, [selectedDrugs]); + + return ( + + + {/* Header */} + + + + + + + Combo Matrix + Drug Interaction Analyzer + + + + + + + setLegendOpen(false)} /> + + {/* Layout */} + + + {/* LEFT: Analyzer */} + + setSelectedDrugs([])} + /> + + {/* Prompt when empty */} + {!result && ( + + + + + Ready to Analyze + + Select 2 substances from the list. + + + + + )} + + + {/* RIGHT: Grid */} + + {/* Search Bar */} + + + + setSearchTerm(e.target.value)} + /> + + + + {filteredDrugs.length === 0 ? ( + No substances found. + ) : ( + + {filteredDrugs.map((drug) => { + const isSelected = selectedDrugs.includes(drug); + const isDimmed = selectedDrugs.length === 2 && !isSelected; + return ( + + + + ); + })} + + )} + + + + ); +}; + +// --- APP WRAPPER --- +const DrugInteractionChecker = () => { + const [mode, setMode] = useState<"light" | "dark">("dark"); + + const toggleColorMode = () => { + setMode((prev) => (prev === "light" ? "dark" : "light")); + }; + + const theme = useMemo(() => getAppleTheme(mode), [mode]); + + return ( + + + + + + + {/* New TripSit Header Component */} + + + + + + ); +}; + +export default DrugInteractionChecker; diff --git a/src/components/Factsheets.tsx b/src/components/Factsheets.tsx index 207124f..ef8e0e4 100644 --- a/src/components/Factsheets.tsx +++ b/src/components/Factsheets.tsx @@ -1,4 +1,7 @@ + + /* eslint-disable no-underscore-dangle */ // We use this because we have the _unit property +/* eslint-disable react/no-unstable-nested-components */ /* eslint-disable sonarjs/no-duplicate-string */ // Make things easier to read /* Welcome Developers to TripSit's Factsheets, brought to you by THC and spite. @@ -15,415 +18,754 @@ It creates charts using ApexCharts: https://apexcharts.com/ Pull requests are welcome! If you have any questions, feel free to ask in #dev on the TripSit Discord: https://discord.gg/tripsit */ -import React, { useMemo } from "react"; +import React, { useMemo, useState, createContext, useContext, useEffect, useRef, useCallback, memo } from "react"; import { MaterialReactTable, useMaterialReactTable, type MRT_ColumnDef, + type MRT_PaginationState, + type MRT_SortingState, } from "material-react-table"; import { IconButton, Tooltip, Typography, - Card, - CardContent, + Chip, + Box, + ThemeProvider, + createTheme, + CssBaseline, + alpha, + Accordion, + AccordionSummary, + AccordionDetails, + Button, + useTheme, + InputBase, + Paper, + Collapse, + GlobalStyles, } from "@mui/material"; -import { Accordion, AccordionItem } from "@nextui-org/react"; import RefreshIcon from "@mui/icons-material/Refresh"; +import ExpandMoreIcon from "@mui/icons-material/ExpandMore"; +import DarkModeIcon from "@mui/icons-material/DarkMode"; +import LightModeIcon from "@mui/icons-material/LightMode"; +import SearchIcon from "@mui/icons-material/Search"; +import BiotechIcon from "@mui/icons-material/Biotech"; +import KeyboardArrowRightIcon from '@mui/icons-material/KeyboardArrowRight'; import { QueryClient, QueryClientProvider, keepPreviousData, useQuery, -} from "@tanstack/react-query"; // note: this is TanStack Rea`ct Query V5 -import { Category, Drug } from "tripsit_drug_db"; +} from "@tanstack/react-query"; // note: this is TanStack React Query V5 +import { Drug } from "tripsit_drug_db"; import { AdapterDateFns } from "@mui/x-date-pickers/AdapterDateFnsV3"; import { LocalizationProvider } from "@mui/x-date-pickers/LocalizationProvider"; import Grid from "@mui/material/Grid"; import KofiButton from "kofi-button"; -import UnfoldMoreDoubleIcon from "@mui/icons-material/UnfoldMoreDouble"; -import UnfoldLessDoubleIcon from "@mui/icons-material/UnfoldLessDouble"; import PatreonButton from "./Patreon"; import addDictionaryDefs from "./addDictionaryDefs"; - import dictionary from "../assets/dictionary.json"; import GithubButton from "./Github"; import DrugInfoCard from "./DrugInfo"; -// If you want to debug a specific drug, change the below variable to the name of the drug -// and then use the commented-out code below that to display what you need to debug -// eslint-disable-next-line @typescript-eslint/no-unused-vars -// const debugDrug = "cocaine"; -// if (drugData.original.name === debugDrug) { -// console.log(`roaString: ${JSON.stringify(roaString, null, 2)}`); -// } +const ColorModeContext = createContext({ toggleColorMode: () => {} }); -// This appears at the top and can contain any information you want -// We can use this for announcements or updates -const InfoBar = ( - // We use the accordion item to make it collapsible - - - isOpen ? : - } - > - - - - - - - TripSit's factsheets are meticulously crafted to deliver - clear, concise, and reliable information about various - substances. Primarily designed for educational purposes, these - factsheets should not be interpreted as medical advice. -

-

- - Your safety is paramount. We encourage you verify - information from multiple sources before making decisions - about substance use. - -

-

- The content presented here is sourced from our comprehensive{" "} - drug database. - If you notice something that needs updating or have additional - information, please{" "} - - submit an issue - {" "} - along with your sources. We're committed to keeping our - data accurate and up-to-date. -

-

- Are you a web developer with ideas to enhance this page? Great - news – it's open source! Dive into our{" "} - - GitHub repo - {" "} - and contribute to the evolution of this resource. Your - expertise can make a significant impact! - - - - - - - - - - - - - - - - - - - - - - -); - -// Function to add styling to categories within a given text. -// It processes the text to highlight each category word with specific styles. -const addCategoryStyle = (text: string | undefined) => { - // Return an empty string if the input text is undefined - if (text === undefined) { - return ""; - } - - // Define a mapping of category names to their respective color styles - // Each category has a background color and a border color - // You can optionally also specify a text color, usually for light backgrounds - const categoryColors = { - psychedelic: { - "background-color": "#00A388", - "border-color": "#00A388", - }, - opioid: { - "background-color": "#C0D9AF", - "border-color": "#C0D9AF", - }, - stimulant: { - "background-color": "#31B0D5", - "border-color": "#31B0D5", - }, - dissociative: { - "background-color": "#9b59b6", - "border-color": "#9b59b6", - }, - benzodiazepine: { - "background-color": "#bd07c2", - "border-color": "#bd07c2", - }, - "research-chemical": { - "background-color": "#EC971F", - "border-color": "#EC971F", - }, - "habit-forming": { - "background-color": "#e67e22", - "border-color": "#e67e22", +const getAppleTheme = (mode: "light" | "dark") => + createTheme({ + palette: { + mode, + background: { + default: mode === "light" ? "#F5F5F7" : "#000000", + paper: mode === "light" ? "#FFFFFF" : "#1C1C1E", + }, + text: { + primary: mode === "light" ? "#000000" : "#FFFFFF", + secondary: mode === "light" ? "#3C3C43" : "#EBEBF5", + }, + primary: { + main: mode === "light" ? "#0071E3" : "#0A84FF", + }, + warning: { + main: '#ffeb3b', + contrastText: '#000000', + }, + divider: mode === "light" ? "rgba(0, 0, 0, 0.1)" : "rgba(255, 255, 255, 0.15)", }, - depressant: { - "background-color": "#C9302C", - "border-color": "#C9302C", + typography: { + fontFamily: '-apple-system, BlinkMacSystemFont, "SF Pro Text", "SF Pro Display", "Segoe UI", Roboto, Helvetica, Arial, sans-serif', + h6: { fontWeight: 600, letterSpacing: "-0.005em" }, + body1: { fontSize: "0.95rem", lineHeight: 1.5 }, + body2: { fontSize: "0.85rem" }, + button: { textTransform: "none", fontWeight: 500 }, }, - tentative: { - "background-color": "#FFFF9D", - "border-color": "#FFFF9D", - color: "#001713", // Optional text color property + shape: { borderRadius: 12 }, + components: { + MuiCssBaseline: { + styleOverrides: { + html: { + scrollbarColor: mode === "dark" ? "#424242 #1c1c1e" : "#d1d1d1 #f5f5f7", + }, + "*::-webkit-scrollbar": { width: "10px", height: "10px" }, + "*::-webkit-scrollbar-track": { background: "transparent" }, + "*::-webkit-scrollbar-thumb": { + backgroundColor: mode === "dark" ? "rgba(255,255,255,0.2)" : "rgba(0,0,0,0.2)", + borderRadius: "10px", + border: "2px solid transparent", + backgroundClip: "content-box", + }, + "*::-webkit-scrollbar-thumb:hover": { + backgroundColor: mode === "dark" ? "rgba(255,255,255,0.3)" : "rgba(0,0,0,0.3)", + }, + }, + }, + MuiMenu: { + styleOverrides: { + paper: { + backgroundColor: mode === "light" ? "#FFFFFF" : "#2C2C2E", + backgroundImage: "none", + border: `1px solid ${mode === "light" ? "rgba(0,0,0,0.1)" : "rgba(255,255,255,0.1)"}`, + }, + }, + }, + MuiMenuItem: { + styleOverrides: { + root: { + color: mode === "light" ? "#000000" : "#FFFFFF", + "&:hover": { + backgroundColor: mode === "light" ? "rgba(0,0,0,0.04)" : "rgba(255,255,255,0.1)", + }, + }, + }, + }, + MuiPaper: { + styleOverrides: { + root: { backgroundImage: "none", boxShadow: "none" }, + }, + }, + MuiTooltip: { + styleOverrides: { + tooltip: { + backdropFilter: "blur(20px)", + backgroundColor: mode === "light" ? "rgba(255, 255, 255, 0.9)" : "rgba(30, 30, 30, 0.9)", + color: mode === "light" ? "#000" : "#fff", + borderRadius: 8, + boxShadow: "0 4px 12px rgba(0,0,0,0.15)", + }, + }, + }, }, - } as { - [key in Category]: { - "background-color": string; - "border-color": string; - color?: string; // Example of an additional text color property - }; - }; + }); + +const GlobalStylesOverride = () => { + const theme = useTheme(); + const isDark = theme.palette.mode === 'dark'; + + return ( + + ); +}; + +const MeshGradient = () => { + const theme = useTheme(); + const isDark = theme.palette.mode === 'dark'; + return ( + + ) +} + +// Map category names to color styles +// Each category has a defined dark and light mode color +const CATEGORY_COLORS: Record = { + psychedelic: { dark: "#30D158", light: "#34C759" }, + stimulant: { dark: "#40CBE0", light: "#32ADE6" }, + depressant: { dark: "#FF453A", light: "#FF3B30" }, + dissociative: { dark: "#BF5AF2", light: "#AF52DE" }, + benzodiazepine: { dark: "#FF375F", light: "#FF2D55" }, + opioid: { dark: "#30D158", light: "#28CD41" }, + cannabinoid: { dark: "#30DB5B", light: "#30D158" }, + common: { dark: "#5E5CE6", light: "#5856D6" }, + "research-chemical": { dark: "#FF9F0A", light: "#FF9500" }, +}; + +const getCategoryStyle = (cat: string, isDark: boolean) => { + const colorSet = CATEGORY_COLORS[cat]; + if (!colorSet) return isDark ? "#8E8E93" : "#8E8E93"; + return isDark ? colorSet.dark : colorSet.light; +} +const formatCategory = (text: string) => text.replace(/-/g, " ").replace(/\b\w/g, (l) => l.toUpperCase()); + +// Styles and renders category pills +// Highlighting based on category mapping with theme support +const CategoryPills = memo(({ text, mode }: { text: string | undefined; mode: string }) => { + if (!text) return null; // Split the input text into individual words - const words = text.split(" "); - - return words.map((word, index) => { - // Remove the comma, we need to keep hyphens though: - const cleanWord = word.replace(/,/g, "").toLowerCase(); - - // Check if the word is included in the categoryColors, and if so, add the styles - if (Object.keys(categoryColors).includes(cleanWord)) { - const colorDef = categoryColors[cleanWord as keyof typeof categoryColors]; - const definition = dictionary[cleanWord as keyof typeof dictionary]; - return ( - - + {words.map((word, index) => { + // Remove the comma, we need to keep hyphens though: + const cleanWord = word.trim().toLowerCase(); + + const baseColor = getCategoryStyle(cleanWord, isDark); + const definition = (dictionary as Record)[cleanWord]; + + return ( + + + + ); + })} + + ); +}); + +const ReadMoreCell = memo(({ text }: { text: string | undefined }) => { + const [expanded, setExpanded] = useState(false); + const theme = useTheme(); + const isDark = theme.palette.mode === 'dark'; + const content = useMemo(() => text ? addDictionaryDefs(text) : null, [text]); + + if (!text) return No summary available; + const isLong = text.length > 200; + + return ( + { + // Allow text selection without triggering row click + if (window.getSelection()?.toString().length) { + e.stopPropagation(); + } + }}> + + {content} + + {isLong && ( + + )} + + ); +}); - // If the word is not included in the categoryColors, just return the word - // This should not happen in practice, but it's here just in case - return `${word} `; - }); +// This appears at the top and can contain any information you want +// We can use this for announcements or updates +const InfoBar = () => { + const theme = useTheme(); + return ( + + {/* We use the accordion item to make it collapsible */} + + } sx={{ minHeight: 64, px: 3 }}> + + + + + + TripSit Database + Harm reduction factsheets + + + + + + + + TripSit's factsheets are meticulously crafted to deliver clear, concise, and reliable information about various substances. Primarily designed for educational purposes, these factsheets should not be interpreted as medical advice. +

+ Your safety is paramount. We encourage you verify information from multiple sources before making decisions about substance use. +

+ The content presented here is sourced from our comprehensive drug database. If you notice something that needs updating or have additional information, please submit an issue along with your sources. We're committed to keeping our data accurate and up-to-date. +

+ Are you a web developer with ideas to enhance this page? Great news – it's open source! Dive into our GitHub repo and contribute to the evolution of this resource. Your expertise can make a significant impact! + + + + + + + + + + + + + + ); +}; + +const AppleSearchBar = ({ + value, + onChange, +}: { + value: string, + onChange: (val: string) => void, +}) => { + const theme = useTheme(); + const isDark = theme.palette.mode === 'dark'; + const inputRef = useRef(null); + + return ( + e.preventDefault()} + onClick={() => inputRef.current?.focus()} + sx={{ + display: 'flex', + alignItems: 'center', + width: '100%', + maxWidth: 480, + height: 40, + borderRadius: '10px', + backgroundColor: isDark ? 'rgba(118, 118, 128, 0.24)' : 'rgba(118, 118, 128, 0.12)', + transition: 'all 0.2s cubic-bezier(0.4, 0, 0.2, 1)', + border: '1px solid transparent', + px: 1.5, + cursor: 'text', + '&:focus-within': { + backgroundColor: isDark ? '#000' : '#fff', + boxShadow: `0 0 0 3px ${alpha(theme.palette.primary.main, 0.2)}`, + border: `1px solid ${theme.palette.primary.main}`, + } + }} + > + + onChange(e.target.value)} + /> + + ); }; -const Factsheets = () => { - const { - data: { data = [], meta } = {}, // your data and api response will probably be different - isError, - isRefetching, - isLoading, - refetch, - } = useQuery<{ - data: Array; - meta: { - totalRowCount: number; - }; - }>({ - queryKey: ["table-data"], - queryFn: async () => { - let drugList = [] as Drug[]; - const response = await fetch( - // TripSit's drug database file - // This is fetched every time the user loads the page to ensure they have the latest data - "https://raw.githubusercontent.com/TripSit/drugs/main/drugs.json", - ); - drugList = Object.values( - (await response.json()) as { [key: string]: Drug }, - ); - return { - data: drugList, - meta: { - totalRowCount: drugList.length, +const FactsheetsTable = () => { + const { toggleColorMode } = useContext(ColorModeContext); + const theme = useTheme(); + const isDark = theme.palette.mode === 'dark'; + const tableContainerRef = useRef(null); + + const [globalFilter, setGlobalFilter] = useState(''); + const [sorting, setSorting] = useState([]); + + const [pagination, setPagination] = useState({ + pageIndex: 0, + pageSize: 50, + }); + + const { data: rawData = [], isError, isRefetching, isLoading, refetch } = useQuery({ + queryKey: ["table-data"], + queryFn: async () => { + // TripSit's drug database file + // This is fetched every time the user loads the page to ensure they have the latest data + const response = await fetch("https://raw.githubusercontent.com/TripSit/drugs/main/drugs.json"); + const json = await response.json(); + return Object.values(json) as Drug[]; }, - }; - }, - placeholderData: keepPreviousData, - }); + placeholderData: keepPreviousData, + staleTime: Infinity, + }); - // Define the columns - const columns = useMemo[]>( - // column definitions... - () => [ - { - accessorKey: "pretty_name", - header: "Name", - filterVariant: "text", - size: 180, // This is the default value, but it stops the column from changing when the table is resized - }, - { - accessorFn: (row) => { - if (row.aliases === undefined) { - return ""; + const data = useMemo(() => rawData, [rawData]); + + // If you want to debug a specific drug, change the below variable to the name of the drug + // and then use the commented-out code below that to display what you need to debug + // eslint-disable-next-line @typescript-eslint/no-unused-vars + // const debugDrug = "cocaine"; + // if (drugData.original.name === debugDrug) { + // console.log(`roaString: ${JSON.stringify(roaString, null, 2)}`); + // } + + const fetchMoreOnBottomReached = useCallback( + (containerRefElement?: HTMLDivElement | null) => { + if (containerRefElement) { + const { scrollHeight, scrollTop, clientHeight } = containerRefElement; + if (scrollHeight - scrollTop - clientHeight < 1000) { + if (pagination.pageSize < data.length) { + setPagination((prev) => ({ + ...prev, + pageSize: prev.pageSize + 50, + })); + } + } } - return row.aliases.join(", "); }, - id: "aliases", - header: "Aliases", - filterVariant: "text", - size: 200, - }, - { - accessorFn: (row) => row.properties.categories?.join(", "), - id: "categories", - header: "Categories", - filterVariant: "text", - enableGlobalFilter: false, - size: 180, // This is the default value, but it stops the column from changing when the table is resized - Cell: ({ cell }) => ( - {addCategoryStyle(cell.getValue())} - ), - }, - { - accessorFn: (row) => { - if (row.properties["test-kits"] === undefined) { - return ""; - } - return row.properties["test-kits"]; + [pagination.pageSize, data.length], + ); + + useEffect(() => { + const ref = tableContainerRef.current; + const handler = () => fetchMoreOnBottomReached(ref); + if (ref) ref.addEventListener('scroll', handler); + return () => { if (ref) ref.removeEventListener('scroll', handler); }; + }, [fetchMoreOnBottomReached]); + + + // Define the columns + const columns = useMemo[]>( + // column definitions... + () => [ + { + accessorKey: "pretty_name", + header: "Substance", + size: 130, // This is the default value, but it stops the column from changing when the table is resized + Cell: ({ cell }) => ( + + {cell.getValue()} + + ), + }, + { + accessorFn: (row) => row.aliases?.join(", ") || "", + id: "aliases", + header: "Aliases", + size: 90, // This is the default value, but it stops the column from changing when the table is resized + maxSize: 100, + Cell: ({ cell }) => ( + + {cell.getValue()} + + ), + }, + { + accessorFn: (row) => row.properties.categories?.join(", "), + id: "categories", + header: "Category", + size: 140, // This is the default value, but it stops the column from changing when the table is resized + Cell: ({ cell }) => ()} mode={theme.palette.mode} />, + }, + { + accessorFn: (row) => row.properties.summary, + id: "summary", + header: "Quick Fact", + grow: true, + minSize: 300, + maxSize: 1000, // Make this one bigger because of the long text + Cell: ({ cell }) => ()} />, + }, + ], + [theme.palette.mode] + ); + + const table = useMaterialReactTable({ + columns, + data, + enableStickyHeader: true, + enableTopToolbar: true, + enableToolbarInternalActions: false, + + enableGlobalFilter: true, + enableGlobalFilterRankedResults: true, + onGlobalFilterChange: setGlobalFilter, + autoResetPageIndex: true, + + enableColumnFilters: false, + enableDensityToggle: false, // Need to fix density stuff + enableHiding: false, + enablePagination: true, + enableBottomToolbar: false, + + state: { + isLoading, + showAlertBanner: isError, + showProgressBars: isRefetching, + globalFilter, + pagination, + sorting, }, - id: "reagent_results", - header: "Reagents Results", - filterVariant: "text", - size: 200, - }, - { - accessorFn: (row) => row.formatted_effects?.join(", "), - id: "effects", - header: "Effects", - filterVariant: "text", - enableGlobalFilter: false, - size: 180, // This is the default value, but it stops the column from changing when the table is resized - Cell: ({ cell }) => ( - {addDictionaryDefs(cell.getValue())} - ), - }, - { - accessorFn: (row) => - row.pweffects ? Object.keys(row.pweffects).join(", ") : undefined, - id: "pweffects", - header: "PW Effects", - filterVariant: "text", - enableGlobalFilter: false, - size: 180, // This is the default value, but it stops the column from changing when the table is resized - Cell: ({ cell }) => ( - {addDictionaryDefs(cell.getValue())} + onPaginationChange: setPagination, + onSortingChange: setSorting, + + enableExpandAll: false, + positionExpandColumn: 'first', + muiTableBodyRowProps: ({ row }) => ({ + onClick: (e) => { + const target = e.target as HTMLElement; + if (target.closest('button') || target.closest('a')) { + return; + } + row.toggleExpanded(); + }, + sx: { + cursor: 'pointer', + transition: 'background-color 0.2s', + backgroundColor: row.getIsExpanded() ? alpha(theme.palette.primary.main, 0.04) : 'transparent', + '&:hover': { + backgroundColor: alpha(theme.palette.primary.main, isDark ? 0.08 : 0.04), + }, + }, + }), + displayColumnDefOptions: { + 'mrt-row-expand': { + header: '', + size: 40, + Cell: ({ row }) => ( + { + e.stopPropagation(); + row.toggleExpanded(); + }} + size="small" + sx={{ + opacity: 0.6, + transition: 'transform 0.2s', + transform: row.getIsExpanded() ? 'rotate(90deg)' : 'rotate(0deg)' + }} + > + + + ) + }, + }, + muiTableContainerProps: { + ref: tableContainerRef, + sx: { + maxHeight: 'calc(100vh - 220px)', + borderRadius: '0 0 16px 16px', + } + }, + muiTablePaperProps: { + elevation: 0, + sx: { + borderRadius: "16px", + border: `1px solid ${theme.palette.divider}`, + backgroundColor: alpha(theme.palette.background.paper, 0.7), + backdropFilter: "blur(20px) saturate(180%)", + boxShadow: theme.shadows[1], + overflow: "hidden", + height: 'calc(100vh - 120px)', // This value seems to work the best + display: 'flex', flexDirection: 'column' + }, + }, + muiTableHeadCellProps: { + sx: { + backgroundColor: alpha(theme.palette.background.paper, 0.9), + backdropFilter: "blur(10px)", + color: "text.secondary", + fontWeight: 600, + fontSize: "0.8rem", + borderBottom: `1px solid ${theme.palette.divider}`, + py: 2, + }, + }, + muiTableBodyCellProps: { + sx: { + borderBottom: `1px solid ${theme.palette.divider}`, + py: 1.5, + whiteSpace: 'normal', + wordBreak: 'break-word', + color: 'text.primary', + }, + }, + muiToolbarAlertBannerProps: isError + ? { + color: "error", + children: "Error loading data", + } + : undefined, + renderTopToolbar: () => ( + + + + refetch()} size="small" sx={{ + bgcolor: alpha(theme.palette.text.secondary, 0.1), + '&:hover': { bgcolor: alpha(theme.palette.text.secondary, 0.2) } + }}> + + + + + + {isDark ? : } + + + + + setGlobalFilter(val)} + /> + + + ), - }, - { - accessorFn: (row) => row.properties.summary, - id: "summary", - header: "Summary", - filterVariant: "text", - enableGlobalFilter: true, - size: 900, // Make this one bigger because of the long text - Cell: ({ cell }) => ( - {addDictionaryDefs(cell.getValue())} + renderDetailPanel: ({ row }) => ( + + + {row.original ? DrugInfoCard({ drugData: row.original }) : No details.} + + ), - }, - ], - [], - // end - ); + }); - const table = useMaterialReactTable({ - columns, - data, - enableStickyHeader: true, - enableStickyFooter: true, - enableRowPinning: true, - // enableRowSelection: true, - rowPinningDisplayMode: "top", - enableDensityToggle: true, // Need to fix density stuff - enableTopToolbar: true, - enableTableHead: true, - enableHiding: true, - rowCount: meta?.totalRowCount ?? 0, - state: { - isLoading, - showAlertBanner: isError, - showProgressBars: isRefetching, - }, - getRowId: (row) => row.name, - initialState: { - showColumnFilters: true, - columnVisibility: { - pweffects: false, - effects: false, - reagent_results: false, - }, - // rowPinning: { - // top: ["0"], - // }, - // rowSelection: { - // cocaine: true, - // }, - // expanded: { - // 0: process.env.NODE_ENV === "development", - // }, - }, - muiTablePaperProps: { sx: { height: "100vh" } }, // Takes up 100% of the viewport available - muiTableContainerProps: { sx: { height: "78vh" } }, // This value seems to work the best - muiToolbarAlertBannerProps: isError - ? { - color: "error", - children: "Error loading data", - } - : undefined, - renderTopToolbarCustomActions: () => ( - <> - - refetch()}> - - - - {InfoBar} - - ), - renderDetailPanel: ({ row }) => DrugInfoCard({ drugData: row.original }), - }); + return ( + + + + + ); +} - return ; +const AppWrapper = () => { + // App.tsx or AppProviders file. Don't just wrap this component with QueryClientProvider! Wrap your whole App! + const [mode, setMode] = useState<"light" | "dark">("dark"); + + useEffect(() => { + if (typeof window !== "undefined") { + const saved = localStorage.getItem("tripsit-theme"); + if (saved === "light" || saved === "dark") setMode(saved); + } + }, []); + + useEffect(() => { + localStorage.setItem("tripsit-theme", mode); + }, [mode]); + + const colorMode = useMemo(() => ({ + toggleColorMode: () => setMode((prev) => (prev === "light" ? "dark" : "light")), + }), []); + + const theme = useMemo(() => getAppleTheme(mode), [mode]); + + return ( + + + + + + + + + + + + + ); }; -const ExamplePage = () => ( - // App.tsx or AppProviders file. Don't just wrap this component with QueryClientProvider! Wrap your whole App! - - - - - -); - -export default ExamplePage; +export default AppWrapper; diff --git a/src/components/combos.json b/src/components/combos.json new file mode 100644 index 0000000..7935b64 --- /dev/null +++ b/src/components/combos.json @@ -0,0 +1,9053 @@ +{ + "2c-t-x": { + "2c-x": { + "status": "Caution" + }, + "5-meo-xxt": { + "note": "Both classes of compounds can be unpredictable alone", + "status": "Caution" + }, + "alcohol": { + "note": "Both these classes of compound can interact unpredictably. Caution should be exercised.", + "status": "Low Risk & Decrease" + }, + "amphetamines": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences. In extreme cases, they can result in severe vasoconstriction, tachycardia, hypertension, and heart failure.", + "status": "Unsafe" + }, + "amt": { + "status": "Dangerous" + }, + "benzodiazepines": { + "status": "Low Risk & Decrease" + }, + "caffeine": { + "note": "High doses of caffeine may cause anxiety which is less manageable when tripping, and since both are stimulating the combination may cause some physical discomfort.", + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "cocaine": { + "note": "Cocaine and 2c-t-x both provide considerable stimulation. When combined they can result in severe vasoconstriction, tachycardia, hypertension, and in extreme cases heart failure.", + "status": "Unsafe" + }, + "dextromethorphan": { + "status": "Unsafe" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "dox": { + "status": "Caution" + }, + "ghb/gbl": { + "status": "Low Risk & Decrease" + }, + "ketamine": { + "status": "Low Risk & Synergy" + }, + "lithium": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + } + ], + "status": "Dangerous" + }, + "lsd": { + "status": "Low Risk & Synergy" + }, + "maois": { + "note": "MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably, which could be dangerous given the unpredictability of the 2C-T-x series", + "status": "Caution" + }, + "mdma": { + "status": "Caution" + }, + "mescaline": { + "status": "Caution" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "status": "Caution" + }, + "nbomes": { + "status": "Caution" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "note": "No expected interactions, some opioids have serotonin action, and could lead to Serotonin Syndrome or a seizure. These are pretty much only to Pentazocine, Methadone, Tramadol, Tapenatdol.", + "status": "Low Risk & No Synergy" + }, + "pcp": { + "status": "Dangerous" + }, + "ssris": { + "status": "Low Risk & Decrease" + }, + "tramadol": { + "status": "Unsafe" + } + }, + "2c-x": { + "2c-t-x": { + "status": "Caution" + }, + "5-meo-xxt": { + "note": "The 5-MeO psychedelics can interact unpredictably to potentiate other psychedelics", + "status": "Caution" + }, + "alcohol": { + "status": "Low Risk & Decrease" + }, + "amphetamines": { + "note": "The anxiogenic and focusing effects of stimulants increase the chance of unpleasant thought loops. The combination is generally unnecessary because of the stimulating effects of psychedelics. Combination of the stimulating effects may be uncomfortable.", + "status": "Caution" + }, + "amt": { + "status": "Dangerous" + }, + "benzodiazepines": { + "status": "Low Risk & Decrease" + }, + "caffeine": { + "note": "High doses of caffeine may cause anxiety which is less manageable when tripping, and since both are stimulating the combination may cause some physical discomfort.", + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "cocaine": { + "note": "The anxiogenic and focusing effects of stimulants increase the chance of unpleasant thought loops. The combination is generally unnecessary because of the stimulating effects of psychedelics. Combination of the stimulating effects may be uncomfortable.", + "status": "Caution" + }, + "dextromethorphan": { + "status": "Low Risk & Synergy" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "dox": { + "status": "Caution" + }, + "ghb/gbl": { + "status": "Low Risk & Decrease" + }, + "ketamine": { + "status": "Low Risk & Synergy" + }, + "lithium": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + } + ], + "status": "Dangerous" + }, + "lsd": { + "status": "Low Risk & Synergy" + }, + "maois": { + "note": "MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably", + "status": "Caution" + }, + "mdma": { + "status": "Low Risk & Synergy" + }, + "mescaline": { + "status": "Caution" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "status": "Low Risk & Synergy" + }, + "nbomes": { + "status": "Caution" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "status": "Low Risk & No Synergy" + }, + "pcp": { + "status": "Low Risk & Synergy" + }, + "pregabalin": { + "note": "Pregabalin may reduce the anxiety and other possible side effects of 2C-X drugs. Additionally, the combination may increase inhibition, dizziness, and risk of injury.", + "sources": [ + { + "author": "Cross, A. L., Viswanath, O., & Sherman, A. L. (2025)", + "title": "Pregabalin. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK470341/" + }, + { + "author": "Gil-Martins, E., Barbosa, D. J., Borges, F., Remião, F., & Silva, R. (2025)", + "title": "Toxicodynamic insights of 2C and NBOMe drugs – Is there abuse potential? Toxicology Reports, 14, 101890.", + "url": "https://doi.org/10.1016/j.toxrep.2025.101890" + } + ], + "status": "Low Risk & Synergy" + }, + "ssris": { + "status": "Low Risk & Decrease" + }, + "tramadol": { + "note": "Tramadol is well known to lower seizure threshold and psychedelics raise the risk of seizures.", + "status": "Unsafe" + } + }, + "5-meo-xxt": { + "2c-t-x": { + "note": "Both classes of compounds can be unpredictable alone", + "status": "Caution" + }, + "2c-x": { + "note": "The 5-MeO psychedelics can interact unpredictably to potentiate other psychedelics", + "status": "Caution" + }, + "alcohol": { + "status": "Low Risk & Decrease" + }, + "amphetamines": { + "note": "The anxiogenic and focusing effects of stimulants increase the chance of unpleasant thought loops. The combination is generally unnecessary because of the stimulating effects of psychedelics. ", + "status": "Unsafe" + }, + "amt": { + "status": "Dangerous" + }, + "benzodiazepines": { + "status": "Low Risk & Decrease" + }, + "caffeine": { + "note": "High doses of caffeine may cause anxiety which is less manageable when tripping, and since both are stimulating the combination may cause some physical discomfort.", + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "cocaine": { + "note": "The anxiogenic and focusing effects of stimulants increase the chance of unpleasant thought loops. The combination is generally unnecessary because of the stimulating effects of psychedelics. ", + "status": "Unsafe" + }, + "dextromethorphan": { + "note": "Little information exists about this combination.", + "status": "Unsafe" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "dox": { + "note": "The 5-MeO class of tryptamines can be unpredictable in their interactions, particularly increasing the risk of unpleasant physical side effects.", + "status": "Caution" + }, + "ghb/gbl": { + "status": "Low Risk & Decrease" + }, + "ketamine": { + "status": "Low Risk & Synergy" + }, + "lsd": { + "status": "Low Risk & Synergy" + }, + "maois": { + "status": "Dangerous" + }, + "mdma": { + "note": "Some of the 5-MeO tryptamines are a bit unpredictable and should be mixed with MDMA with care", + "status": "Caution" + }, + "mescaline": { + "note": "The 5-MeO class of tryptamines can be unpredictable in their interactions", + "status": "Caution" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "note": "Little information exists about this combination.", + "status": "Low Risk & Synergy" + }, + "nbomes": { + "note": "The 5-MeO class of tryptamines can be unpredictable in their interactions and the NBOMes are known to be unpredictable even alone. This combination is best avoided", + "status": "Caution" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "status": "Low Risk & No Synergy" + }, + "pcp": { + "status": "Dangerous" + }, + "pregabalin": { + "note": "Caution should be given due to 5-MeO-xxT drugs stimulating effects and pregabalin’s seizure concerns at higher dosages. Pregabalin may reduce the vasoconstriction, anxiety, and other side effects of 5-MeO-xxT drugs. Additionally, Pregabalin may increase 5-MeO-xxT drugs inhibition and risk of injury.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Altuncı, Y. A., Aydoğdu, M., Açıkgöz, E., Güven, Ü., Düzağaç, F., Atasoy, A., Dağlıoğlu, N., & Akgür, S. A. (2021)", + "title": "New Psychoactive Substance 5-MeO-MiPT In vivo Acute Toxicity and Hystotoxicological Study. Balkan Medical Journal, 38(1), 34–42.", + "url": "https://doi.org/10.4274/balkanmedj.galenos.2020.2019.11.68" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Reckweg, J. T., Uthaug, M. V., Szabo, A., Davis, A. K., Lancelotta, R., Mason, N. L., & Ramaekers, J. G. (2022)", + "title": "The clinical pharmacology and potential therapeutic applications of 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeO‐DMT). Journal of Neurochemistry, 162(1), 128–146.", + "url": "https://doi.org/10.1111/jnc.15587" + }, + { + "author": "Rickli, A., Moning, O. D., Hoener, M. C., & Liechti, M. E. (2016)", + "title": "Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 26(8), 1327–1337.", + "url": "https://doi.org/10.1016/j.euroneuro.2016.05.001" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Soto-Angona, Ó., Fortea, A., Fortea, L., Martínez-Ramírez, M., Santamarina, E., López, F. J. G., Knudsen, G. M., & Ona, G. (2024)", + "title": "Do classic psychedelics increase the risk of seizures? A scoping review. European Neuropsychopharmacology, 85, 35–42.", + "url": "https://doi.org/10.1016/j.euroneuro.2024.05.002" + } + ], + "status": "Caution" + }, + "ssris": { + "status": "Low Risk & Decrease" + }, + "tramadol": { + "status": "Unsafe" + } + }, + "alcohol": { + "2c-t-x": { + "note": "Both these classes of compound can interact unpredictably. Caution should be exercised.", + "status": "Low Risk & Decrease" + }, + "2c-x": { + "status": "Low Risk & Decrease" + }, + "5-meo-xxt": { + "status": "Low Risk & Decrease" + }, + "amphetamines": { + "note": "Drinking on stimulants is risky because the sedative effects of the alcohol are reduced, and these are what the body uses to gauge drunkenness. This typically leads to excessive drinking with greatly reduced inhibitions, high risk of liver damage and increased dehydration. They will also allow you to drink past a point where you might normally pass out, increasing the risk. If you do decide to do this then you should set a limit of how much you will drink each hour and stick to it, bearing in mind that you will feel the alcohol and the stimulant less. Extended release formulations may severely impede sleep, further worsening the hangover.", + "status": "Caution" + }, + "amt": { + "note": "aMT has a broad mechanism of action in the brain and so does alcohol so the combination can be unpredictable", + "status": "Caution" + }, + "benzodiazepines": { + "note": "Ethanol ingestion may potentiate the CNS effects of many benzodiazepines. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Blacking out and memory loss is almost certain.", + "status": "Dangerous" + }, + "caffeine": { + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "note": "In excess, this combination can cause nausea.", + "status": "Low Risk & Synergy" + }, + "cocaine": { + "note": "Cocaine can decrease some of the intoxicating effects of alcohol, causing some people to drink more than they otherwise would, which leads to greater behavioral and physical health risks. There is also some debate about cocaethylene, a metabolite produced when combining alcohol and cocaine, with some researchers positing that it is more cardiotoxic than cocaine on its own. Use moderation when combining these substances.", + "sources": [ + { + "author": "McCance-Katz, E. F., Kosten, T. R., & Jatlow, P. ", + "title": "Concurrent use of cocaine and alcohol is more potent and potentially more toxic than use of either alone—A multiple-dose study.", + "url": "https://doi.org/10.1016/S0006-3223(97)00426-5" + }, + { + "author": "Pergolizzi, J., Breve, F., Magnusson, P., LeQuang, J. A. K., & Varrassi, G.", + "title": "Cocaethylene: When cocaine and alcohol are taken together. (2022)", + "url": "https://doi.org/10.7759/cureus.22498" + }, + { + "author": "Shastry, S., Manoochehri, O., Richardson, L. D., & Manini, A. F. ", + "title": "Cocaethylene cardiotoxicity in emergency department patients with acute drug overdose.", + "url": "https://doi.org/10.1111/acem.14584" + }, + { + "author": "Wiener, S. E., Sutijono, D., Moon, C. H., Subramanian, R. A., Calaycay, J., Rushbrook, J. I., & Zehtabchi, S.", + "title": "Patients with detectable cocaethylene are more likely to require intensive care unit admission after trauma. ", + "url": "https://doi.org/10.1016/j.ajem.2009.06.014" + } + ], + "status": "Unsafe" + }, + "dextromethorphan": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place the affected individual in the recovery position to prevent vomit aspiration from excess. Additionally, CNS depression can lead to difficulty breathing. Avoid on anything higher than 1st plateau.", + "status": "Dangerous" + }, + "diphenhydramine": { + "note": "The two substances potentiate each other strongly and unpredictably, and may rapidly lead to unconsciousness. They both increase each other's side effects such as ataxia, sedation, and CNS depression. Blackouts and memory loss are significantly increased. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position. Alcohol may also increase the deliriant effects of diphenhydramine. It should also be noted if the individual consuming alcohol typically has a flushing response to alcohol, diphenhydramine may reduce the reaction and mask some of the effects of the alcohol.", + "sources": [ + { + "author": "ScienceDirect", + "title": "Diphenhydramine - an overview (2024)", + "url": "https://www.sciencedirect.com/topics/chemistry/diphenhydramine" + }, + { + "author": "ScienceDirect", + "title": "Ethanol - an overview (2024)", + "url": "https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/ethanol" + }, + { + "author": "Miller, N. S., Goodwin, D. W., Jones, F. C., Gabrielli, W. F., Pardo, M. P., Anand, M. M., & Hall, T. B.", + "title": "Antihistamine blockade of alcohol-induced flushing in orientals. Journal of Studies on Alcohol, 49(1), 16-20 (1988)", + "url": "https://doi.org/10.15288/jsa.1988.49.16" + }, + { + "author": "Sicari, V., & Zabbo, C. P.", + "title": "Diphenhydramine. In StatPearls. StatPearls Publishing (2024)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + }, + { + "author": "Weathermon, R., & Crabb, D. W.", + "title": "Alcohol and Medication Interactions. Alcohol Research & Health, 23(1), 40-54 (1999)", + "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761694/" + } + ], + "status": "Dangerous" + }, + "dmt": { + "status": "Low Risk & Decrease" + }, + "dox": { + "note": "Drinking on stimulants is risky because the sedative effects of the alcohol are reduced, and these are what the body uses to gauge drunkenness. This typically leads to excessive drinking with greatly reduced inhibitions, high risk of liver damage and increased dehydration. They will also allow you to drink past a point where you might normally pass out, increasing the risk.", + "status": "Low Risk & Decrease" + }, + "ghb/gbl": { + "note": "Even in very low doses this combination rapidly leads to memory loss, severe ataxia and unconsciousness. There is a high risk of vomit aspiration while unconscious.", + "status": "Dangerous" + }, + "ketamine": { + "note": "Both substances cause ataxia and bring a very high risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.", + "status": "Dangerous" + }, + "lsd": { + "status": "Low Risk & Decrease" + }, + "maois": { + "note": "Tyramine found in many alcoholic beverages can have dangerous reactions with MAOIs, causing an increase in blood pressure.", + "status": "Unsafe" + }, + "mdma": { + "note": "The combination of MDMA and alcohol may increase strain on the cardiovascular system and lead to increased alcohol consumption. MDMA may also impair one's ability to recognize their level of drunkenness, leading to increased alcohol consumption and poor decision-making. Alcohol may also increase the risk of dehydration and hyperthermia (increased body temperature) when combined with MDMA.", + "sources": [ + { + "author": "Hamida, S. B., Plute, E., Cosquer, B., Kelche, C., Jones, B. C., & Cassel, J.-C. ", + "title": "Interactions between ethanol and cocaine, amphetamine, or MDMA in the rat: thermoregulatory and locomotor effects. (2008)", + "url": "https://doi.org/10.1007/s00213-007-1007-5" + }, + { + "author": "Ramaekers, J. G., & Kuypers, K. P. C.", + "title": "Acute Effects of 3,4-Methylenedioxymethamphetamine (MDMA) on Behavioral Measures of Impulsivity: Alone and in Combination with Alcohol. (2006)", + "url": "https://doi.org/10.1038/sj.npp.1300894" + }, + { + "author": "Hernández-López, C., Farré, M., Roset, P. N., Menoyo, E., Pizarro, N., Ortuño, J., Torrens, M., Camı́, J., & Torre, R. de la.", + "title": "3,4-Methylenedioxymethamphetamine (Ecstasy) and Alcohol Interactions in Humans: Psychomotor Performance, Subjective Effects, and Pharmacokinetics. (2002)", + "url": "https://doi.org/10.1124/jpet.300.1.236" + }, + { + "author": "van Amsterdam, J., Brunt, T. M., Pierce, M., & van den Brink, W.", + "title": "Hard Boiled: Alcohol Use as a Risk Factor for MDMA-Induced Hyperthermia: a Systematic Review. (2021)", + "url": "https://doi.org/10.1007/s12640-021-00416-z" + } + ], + "status": "Caution" + }, + "mescaline": { + "status": "Low Risk & Decrease" + }, + "mushrooms": { + "status": "Low Risk & Decrease" + }, + "mxe": { + "note": "There is a high risk of memory loss, vomiting and severe ataxia from this combination.", + "status": "Dangerous" + }, + "nbomes": { + "status": "Low Risk & Decrease" + }, + "nitrous": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are likely.", + "status": "Caution" + }, + "opioids": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place the affected individual in the recovery position to prevent vomit aspiration from excess. Memory blackouts are likely", + "status": "Dangerous" + }, + "pcp": { + "note": "Details of this combination are not well understood but PCP generally interacts in an unpredictable manner.", + "status": "Unsafe" + }, + "ssris": { + "note": "Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.", + "status": "Caution" + }, + "tramadol": { + "note": "Heavy CNS depressants, risk of seizures. Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place the affected individual in the recovery position to prevent vomit aspiration from excess. Memory blackouts are likely.", + "status": "Dangerous" + } + }, + "amphetamines": { + "2c-t-x": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences. In extreme cases, they can result in severe vasoconstriction, tachycardia, hypertension, and heart failure.", + "status": "Unsafe" + }, + "2c-x": { + "note": "The anxiogenic and focusing effects of stimulants increase the chance of unpleasant thought loops. The combination is generally unnecessary because of the stimulating effects of psychedelics. Combination of the stimulating effects may be uncomfortable.", + "status": "Caution" + }, + "5-meo-xxt": { + "note": "The anxiogenic and focusing effects of stimulants increase the chance of unpleasant thought loops. The combination is generally unnecessary because of the stimulating effects of psychedelics. ", + "status": "Unsafe" + }, + "alcohol": { + "note": "Drinking on stimulants is risky because the sedative effects of the alcohol are reduced, and these are what the body uses to gauge drunkenness. This typically leads to excessive drinking with greatly reduced inhibitions, high risk of liver damage and increased dehydration. They will also allow you to drink past a point where you might normally pass out, increasing the risk. If you do decide to do this then you should set a limit of how much you will drink each hour and stick to it, bearing in mind that you will feel the alcohol and the stimulant less. Extended release formulations may severely impede sleep, further worsening the hangover.", + "status": "Caution" + }, + "amt": { + "status": "Dangerous" + }, + "benzodiazepines": { + "note": "Both can dull each other's effects, so if one wears off before the other it's possible to overdose due to the lack of counteraction", + "status": "Low Risk & Decrease" + }, + "caffeine": { + "note": "This combination of stimulants is not generally necessary and may increase strain on the heart, as well as potentially causing anxiety and greater physical discomfort.", + "status": "Caution" + }, + "cannabis": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "cocaine": { + "note": "This combination of stimulants will increase strain on the heart. It is not generally worth it as cocaine has a mild blocking effect on dopamine releasers like amphetamine", + "status": "Caution" + }, + "dextromethorphan": { + "note": "Both substances raise heart rate, in extreme cases, panic attacks caused by these drugs have led to more serious heart issues.", + "status": "Unsafe" + }, + "diphenhydramine": { + "note": "Amphetamines as a stimulant may mask some of the negative side effects of DPH, leading to delusions of sobriety which has additional concern in states of delirium. The combination of stimulants will increase strain on the heart and may cause some physical discomfort, and has the chance to cause life-threatening cardiovascular issues. The combination may also increase each other's neurotoxicity at higher dosages. The combination may increase anxiety levels and risks of thought loops on higher dosages, in addition to increasing each others negative side effects. Medical and common dosages of each substances are reported to not be a concern. Additionally, it is suggested that DPH potentiates amphetamine psychomotor activation, in addition to other interactions such as potentiation through inhibition of CYP2D6 and histamine H1 and H2 receptors, among other alterations.", + "sources": [ + { + "author": "Berman, S. M.; Kuczenski, R.; McCracken, J. T.; London, E. D.", + "title": "Potential adverse effects of amphetamine treatment on brain and behavior: a review. Molecular Psychiatry, 14(2), 123–142 (2009)", + "url": "https://doi.org/10.1038/mp.2008.90" + }, + { + "author": "Clark, J. H.; Meltzer, E. O.; Naclerio, R. M.", + "title": "Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027 (2025)", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Martin, D.; Le, J. K.", + "title": "Amphetamine. In StatPearls. StatPearls Publishing (2025)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK556103/" + }, + { + "author": "McAtee, K. J.; Brillhart, D.; Barbuto, A. F.; Hiller, H. M.", + "title": "Wide complex tachycardia secondary to massive diphenhydramine overdose: a case report. Journal of Emergency and Critical Care Medicine, 6 (2022)", + "url": "https://doi.org/10.21037/jeccm-21-33" + }, + { + "author": "Mohs, R. C.; Tinklenberg, J. R.; Roth, W. T.; Kopell, B. S.", + "title": "Methamphetamine and diphenhydramine effects on the rate of cognitive processing. Psychopharmacology (1978)", + "url": "https://doi.org/10.1007/BF00428024" + }, + { + "author": "Okuda, T.; Ito, Y.; Nakagawa, N.; Hishinuma, T.; Tsukamoto, H.; Iwabuchi, K.; Watanabe, T.; Kitaichi, K.; Goto, J.; Yanai, K.", + "title": "Drug interaction between methamphetamine and antihistamines: behavioral changes and tissue concentrations of methamphetamine in rats. European Journal of Pharmacology, 505(1), 135–144 (2004)", + "url": "https://doi.org/10.1016/j.ejphar.2004.10.022" + }, + { + "author": "Sicari, V.; Patel, P.; Zabbo, C. P.", + "title": "Diphenhydramine. In StatPearls. StatPearls Publishing (2025)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + }, + { + "author": "Steinkellner, T.; Freissmuth, M.; Sitte, H. H.; Montgomery, T.", + "title": "The ugly side of amphetamines: short- and long-term toxicity of MDMA, methamphetamine and d-amphetamine. Biological Chemistry, 392(0) (2011)", + "url": "https://doi.org/10.1515/BC.2011.016" + }, + { + "author": "Vasan, S.; Murray, B. P.; Olango, G. J.", + "title": "Amphetamine Toxicity. In StatPearls. StatPearls Publishing (2025)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK470276/" + } + ], + "status": "Caution" + }, + "dmt": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "dox": { + "note": "The combined stimulating effects of the two can lead to an uncomfortable body-load, while the focusing effects of amphetamine can easily lead to thought loops. Coming down from amphetamines while the DOx is still active can be quite anxiogenic. ", + "status": "Unsafe" + }, + "ghb/gbl": { + "note": "Stimulants increase respiration rate allowing for a higher dose of sedatives. If the stimulant wears off first then the opiate may overcome the individual and cause respiratory arrest.", + "status": "Caution" + }, + "ketamine": { + "note": "No unexpected interactions, though likely to increase blood pressure but not an issue with sensible doses. Moving around on high doses of this combination may be ill advised due to risk of physical injury.", + "status": "Caution" + }, + "lithium": { + "note": "Lithium may be neuroprotective when taken with amphetamines and lithium may decrease the hyperactive and euphoric effects of amphetamines. Lithium may also decrease some negative side effects of amphetamines. Studies indicate this combination is safe.", + "sources": [ + { + "author": "Ago, Y., Tanaka, T., Kita, Y., Tokumoto, H., Takuma, K., & Matsuda, T.", + "title": "Lithium attenuates methamphetamine-induced hyperlocomotion and behavioral sensitization via modulation of prefrontal monoamine release. (2012)", + "url": "https://doi.org/10.1016/j.neuropharm.2011.10.004" + }, + { + "author": "Gould, T. D., O’Donnell, K. C., Picchini, A. M., & Manji, H. K.", + "title": "Strain Differences in Lithium Attenuation of d-Amphetamine-Induced Hyperlocomotion: A Mouse Model for the Genetics of Clinical Response to Lithium. (2007)", + "url": "https://doi.org/10.1038/sj.npp.1301254" + }, + { + "author": "van Kammen, D. P., Docherty, J. P., Marder, S. R., Rosenblatt, J. E., & Bunney, W. E..", + "title": "Lithium attenuates the activation-euphoria but not the psychosis induced by d-amphetamine in schizophrenia. (1985)", + "url": "https://doi.org/10.1007/BF00431789" + }, + { + "author": "Zhou, Z., Wang, Y., Tan, H., Bharti, V., Che, Y., & Wang, J.-F. ", + "title": "Chronic treatment with mood stabilizer lithium inhibits amphetamine-induced risk-taking manic-like behaviors. (2015)", + "url": "https://doi.org/10.1016/j.neulet.2015.07.027" + }, + { + "author": "Silverstone, P. H., Pukhovsky, A., & Rotzinger, S.", + "title": "Lithium does not attenuate the effects of d-amphetamine in healthy volunteers. (1998)", + "url": "https://doi.org/10.1016/S0165-1781(98)00037-7" + } + ], + "status": "Low Risk & No Synergy" + }, + "lsd": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "maois": { + "note": "MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably. MAO-A inhibitors with amphetamine can lead to hypertensive crises.", + "status": "Dangerous" + }, + "mdma": { + "note": "This combination of stimulants will increase strain on the heart, may cause some physical discomfort, and has the chance to cause cardiovascular issues. The anxiogenic and focusing effects of stimulants can increase the chance of unpleasant thought loops and make the experience more uncomfortable, this combination raises these chances. Amphetamines will increase the neurotoxic effects of MDMA, in addition to causing further concerns of hyperthermia due to the inherent nature of the combination. It will also raise one's body temperature, also likely making the combination more neurotoxic.", + "sources": [ + { + "author": "Kelly J. Clemens, Iain S. McGregor, Glenn E. Hunt, Jennifer L. Cornish", + "title": "MDMA, methamphetamine and their combination: possible lessons for party drug users from recent preclinical research", + "url": "https://doi.org/10.1080/09595230601036945" + }, + { + "author": "Kelly J. Clemens, Iain S. McGregor, Glenn E. Hunt, Jennifer L. Cornish", + "title": "Repeated weekly exposure to MDMA, methamphetamine or their combination: long-term behavioural and neurochemical effects in rats ", + "url": "https://doi.org/10.1016/j.drugalcdep.2006.06.004" + }, + { + "author": "P. Leon Brown, Eugene A. Kiyatkin", + "title": "Brain hyperthermia induced by MDMA (‘ecstasy’): modulation by environmental conditions", + "url": "https://doi.org/10.1111/j.0953-816X.2004.03453.x" + } + ], + "status": "Caution" + }, + "mescaline": { + "note": "The focus and anxiety caused by stimulants is magnified by psychedelics and results in an increased risk of thought loops", + "status": "Caution" + }, + "mushrooms": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "mxe": { + "note": "Risk of tachycardia, hypertension, and manic states", + "status": "Caution" + }, + "nbomes": { + "note": "Amphetamines and NBOMes both provide considerable stimulation. When combined they can result in tachycardia, hypertension, vasoconstriction and in extreme cases heart failure. The anxiogenic and focusing effects of stimulants are also not good in combination with psychedelics as they can lead to unpleasant thought loops. NBOMes are known to cause seizures and stimulants can increase this risk.", + "status": "Unsafe" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "note": "Stimulants increase respiration rate, which can allow for a higher dose of opiates normal . If the stimulant wears off first then the opiate may overcome the individual and cause respiratory arrest.", + "status": "Caution" + }, + "pcp": { + "note": "This combination can easily lead to hypermanic states", + "status": "Unsafe" + }, + "pregabalin": { + "note": "There is a significant risk of seizures from this combination. Amphetamines increase respiration rate allowing for a higher dose of sedatives than normal. If amphetamines wears off first, recreational dosages of pregabalin may overcome the individual and cause respiratory arrest. Both substances at recreational dosages cause strain of the heart and may lead to further dangerous heart complications.", + "sources": [ + { + "author": "Martin, D., & Le, J. K. (2023)", + "title": "Amphetamine. In StatPearls. StatPearls Publishing.", + "url": "https://www.ncbi.nlm.nih.gov/books/NBK556103/" + }, + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + } + ], + "status": "Unsafe" + }, + "ssris": { + "status": "Low Risk & No Synergy" + }, + "tramadol": { + "note": "Tramadol and stimulants both increase the risk of seizures.", + "status": "Dangerous" + } + }, + "amt": { + "2c-t-x": { + "status": "Dangerous" + }, + "2c-x": { + "status": "Dangerous" + }, + "5-meo-xxt": { + "status": "Dangerous" + }, + "alcohol": { + "note": "aMT has a broad mechanism of action in the brain and so does alcohol so the combination can be unpredictable", + "status": "Caution" + }, + "amphetamines": { + "status": "Dangerous" + }, + "benzodiazepines": { + "status": "Low Risk & Decrease" + }, + "caffeine": { + "note": "High doses of caffeine may cause anxiety which is less manageable when tripping, and since both are stimulating the combination may cause some physical discomfort.", + "status": "Caution" + }, + "cannabis": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics. Small amounts can reduce nausea with aMT but take care.", + "status": "Caution" + }, + "cocaine": { + "status": "Dangerous" + }, + "dextromethorphan": { + "status": "Dangerous" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "dox": { + "status": "Dangerous" + }, + "ghb/gbl": { + "status": "Low Risk & Decrease" + }, + "ketamine": { + "status": "Low Risk & Synergy" + }, + "lsd": { + "status": "Low Risk & Synergy" + }, + "maois": { + "note": "aMT is an MAOI on its own. Using enzyme inhibitors can greatly reduce predictability of effects.", + "status": "Dangerous" + }, + "mdma": { + "status": "Dangerous" + }, + "mescaline": { + "status": "Dangerous" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "status": "Dangerous" + }, + "nbomes": { + "status": "Dangerous" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "note": "No unexpected interactions", + "status": "Low Risk & No Synergy" + }, + "pcp": { + "status": "Dangerous" + }, + "ssris": { + "status": "Dangerous" + }, + "tramadol": { + "status": "Dangerous" + } + }, + "benzodiazepines": { + "2c-t-x": { + "status": "Low Risk & Decrease" + }, + "2c-x": { + "status": "Low Risk & Decrease" + }, + "5-meo-xxt": { + "status": "Low Risk & Decrease" + }, + "alcohol": { + "note": "Ethanol ingestion may potentiate the CNS effects of many benzodiazepines. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Blacking out and memory loss is almost certain.", + "status": "Dangerous" + }, + "amphetamines": { + "note": "Both can dull each other's effects, so if one wears off before the other it's possible to overdose due to the lack of counteraction", + "status": "Low Risk & Decrease" + }, + "amt": { + "status": "Low Risk & Decrease" + }, + "caffeine": { + "status": "Low Risk & Decrease" + }, + "cannabis": { + "status": "Low Risk & Decrease" + }, + "cocaine": { + "status": "Low Risk & Decrease" + }, + "dextromethorphan": { + "note": "Small doses of benzos can end a bad trip, but both substances potentiate the ataxia and sedation caused by the other and this can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position.", + "status": "Caution" + }, + "diphenhydramine": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are likely. Low medical doses are unlikely to be of concern.", + "sources": [ + { + "author": "Bounds, Connor G., and Preeti Patel. (2025)", + "title": "Benzodiazepines. StatPearls, StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK470159/" + }, + { + "author": "Montoro, J., et al. (2013)", + "title": "H1 Antihistamines and Benzodiazepines. Pharmacological Interactions and Their Impact on Cerebral Function. Journal of Investigational Allergology & Clinical Immunology, 23 Suppl 1, 17–26.", + "url": "https://pubmed.ncbi.nlm.nih.gov/24672891/" + }, + { + "author": "Sicari, Vincent, et al. (2025)", + "title": "Diphenhydramine. StatPearls, StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + } + ], + "status": "Unsafe" + }, + "dmt": { + "status": "Low Risk & Decrease" + }, + "dox": { + "status": "Low Risk & Decrease" + }, + "ghb/gbl": { + "note": "The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position.", + "status": "Dangerous" + }, + "ketamine": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position.", + "status": "Caution" + }, + "lsd": { + "status": "Low Risk & Decrease" + }, + "maois": { + "status": "Low Risk & Synergy" + }, + "mdma": { + "status": "Low Risk & Decrease" + }, + "mescaline": { + "status": "Low Risk & Decrease" + }, + "mushrooms": { + "status": "Low Risk & Decrease" + }, + "mxe": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place the affected individual in the recovery position to prevent vomit aspiration from excess.", + "status": "Caution" + }, + "nbomes": { + "status": "Low Risk & Decrease" + }, + "nitrous": { + "status": "Low Risk & Decrease" + }, + "opioids": { + "note": "Central nervous system and/or respiratory-depressant effects may be additively or synergistically present. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position Blackouts/memory loss likely", + "status": "Dangerous" + }, + "pcp": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are likely", + "status": "Unsafe" + }, + "ssris": { + "status": "Low Risk & No Synergy" + }, + "tramadol": { + "note": "Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present. Vomit aspiration is a risk when passed out, lay down in recovery position if ingested.", + "status": "Dangerous" + } + }, + "caffeine": { + "2c-t-x": { + "note": "High doses of caffeine may cause anxiety which is less manageable when tripping, and since both are stimulating the combination may cause some physical discomfort.", + "status": "Low Risk & No Synergy" + }, + "2c-x": { + "note": "High doses of caffeine may cause anxiety which is less manageable when tripping, and since both are stimulating the combination may cause some physical discomfort.", + "status": "Low Risk & No Synergy" + }, + "5-meo-xxt": { + "note": "High doses of caffeine may cause anxiety which is less manageable when tripping, and since both are stimulating the combination may cause some physical discomfort.", + "status": "Low Risk & No Synergy" + }, + "alcohol": { + "status": "Low Risk & No Synergy" + }, + "amphetamines": { + "note": "This combination of stimulants is not generally necessary and may increase strain on the heart, as well as potentially causing anxiety and greater physical discomfort.", + "status": "Caution" + }, + "amt": { + "note": "High doses of caffeine may cause anxiety which is less manageable when tripping, and since both are stimulating the combination may cause some physical discomfort.", + "status": "Caution" + }, + "benzodiazepines": { + "status": "Low Risk & Decrease" + }, + "cannabis": { + "status": "Low Risk & No Synergy" + }, + "cocaine": { + "note": "Both stimulants, risk of tachycardia, hypertension, and in extreme cases heart failure.", + "status": "Caution" + }, + "dextromethorphan": { + "note": "High doses of caffeine can potentially exacerbate anxiety, especially during a dissociative experience, due to its stimulating effects. This combination might also lead to physical discomfort. However, individual responses to caffeine can vary significantly, often influenced by factors like habitual versus occasional usage.", + "sources": [ + { + "author": "Chad J Reissig, Lawrence P Carter, Matthew W Johnson, Miriam Z Mintzer, Margaret A Klinedinst, Roland R Griffiths", + "title": "High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens ", + "url": "https://pubmed.ncbi.nlm.nih.gov/22526529/" + }, + { + "author": "Arthur Eumann Mesas, Luz M Leon-Muñoz, Fernando Rodriguez-Artalejo, Esther Lopez-Garcia", + "title": "The effect of coffee on blood pressure and cardiovascular disease in hypertensive individuals: a systematic review and meta-analysis ", + "url": "https://pubmed.ncbi.nlm.nih.gov/21880846/" + }, + { + "author": "M-L Nurminen, L Niittynen, R Korpela & H Vapaatalo", + "title": "Coffee, caffeine and blood pressure: a critical review", + "url": "https://www.nature.com/articles/1600899" + } + ], + "status": "Caution" + }, + "diphenhydramine": { + "note": "Caffeine as a stimulant may mask some negative side effects of DPH, leading to delusions of sobriety, which has additional concerns in states of delirium. The combination of stimulants will increase strain on the heart and may cause some physical discomfort, and has the chance to cause cardiovascular issues such as complex tachycardia. The combination may increase anxiety levels and risks of thought loops at higher dosages, in addition to increasing each other's negative side effects. Medical dosages are reported to not be a concern.", + "sources": [ + { + "author": "Clark, J. H.; Meltzer, E. O.; Naclerio, R. M. (2025)", + "title": "Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027.", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Evans, J.; Richards, J. R.; Battisti, A. S. (2025)", + "title": "Caffeine. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK519490/" + }, + { + "author": "McAtee, K. J.; Brillhart, D.; Barbuto, A. F.; Hiller, H. M. (2022)", + "title": "Wide complex tachycardia secondary to massive diphenhydramine overdose: a case report. Journal of Emergency and Critical Care Medicine, 6(0).", + "url": "https://doi.org/10.21037/jeccm-21-33" + }, + { + "author": "Murray, A.; Traylor, J. (2025)", + "title": "Caffeine Toxicity. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK532910/" + }, + { + "author": "Institute of Medicine (US) Committee on Military Nutrition Research (2001)", + "title": "Pharmacology of Caffeine. In Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. National Academies Press (US).", + "url": "https://www.ncbi.nlm.nih.gov/books/NBK223808/" + }, + { + "author": "Sicari, V.; Patel, P.; Zabbo, C. P. (2025)", + "title": "Diphenhydramine. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + }, + { + "author": "Tharion, W. J.; Kobrick, J. L.; Lieberman, H. R.; Fine, B. J. (1993)", + "title": "Effects of caffeine and diphenhydramine on auditory evoked cortical potentials. Perceptual and Motor Skills, 76(3 Pt 1), 707–715.", + "url": "https://doi.org/10.2466/pms.1993.76.3.707" + } + ], + "status": "Caution" + }, + "dmt": { + "status": "Low Risk & No Synergy" + }, + "dox": { + "note": "High doses of caffeine may cause anxiety which is less manageable when tripping, and since both are stimulating it may cause some physical discomfort.", + "status": "Caution" + }, + "ghb/gbl": { + "status": "Low Risk & No Synergy" + }, + "ketamine": { + "note": "No unexpected interactions.", + "status": "Low Risk & No Synergy" + }, + "lsd": { + "status": "Low Risk & No Synergy" + }, + "maois": { + "status": "Low Risk & No Synergy" + }, + "mdma": { + "note": "Caffeine is not really necessary with MDMA and increases any neurotoxic effects from MDMA", + "status": "Caution" + }, + "mephedrone": { + "note": "This combination of stimulants is not generally necessary and may increase strain on the heart, as well as potentially causing anxiety and great physical discomfort. However, individual responses to caffeine can vary significantly, often influenced by factors like habitual versus occasional usage.", + "sources": [ + { + "author": "Mesas AE, Leon-Muñoz LM, Rodriguez-Artalejo F, Lopez-Garcia E", + "title": " The effect of coffee on blood pressure and cardiovascular disease in hypertensive individuals: a systematic review and meta-analysis ", + "url": "https://doi.org/10.3945/ajcn.111.016667" + }, + { + "author": "Nurminen, ML., Niittynen, L., Korpela, R", + "title": "Coffee, caffeine and blood pressure: a critical review", + "url": "https://doi.org/10.1038/sj.ejcn.1600899" + }, + { + "author": "Institute of Medicine (US) Committee on Military Nutrition Research.", + "title": "Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations.", + "url": "https://www.ncbi.nlm.nih.gov/books/NBK223808/" + }, + { + "author": "Baumann MH, Ayestas MA Jr, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV", + "title": "The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue ", + "url": "https://doi.org/10.1038/npp.2011.304" + }, + { + "author": "Wright MJ Jr, Vandewater SA, Angrish D, Dickerson TJ, Taffe MA", + "title": "Mephedrone (4-methylmethcathinone) and d-methamphetamine improve visuospatial associative memory, but not spatial working memory, in rhesus macaques", + "url": "https://doi.org/10.1111%2Fj.1476-5381.2012.02091.x" + }, + { + "author": "Kehr J, Ichinose F, Yoshitake S, Goiny M, Sievertsson T, Nyberg F, Yoshitake T", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats", + "url": "https://doi.org/10.1111%2Fj.1476-5381.2011.01499.x" + } + ], + "status": "Caution" + }, + "mescaline": { + "note": "High doses of caffeine are uncomfortable and this will be magnified by psychedelics", + "status": "Low Risk & No Synergy" + }, + "mushrooms": { + "status": "Low Risk & No Synergy" + }, + "mxe": { + "note": "No likely interactions", + "status": "Low Risk & No Synergy" + }, + "nbomes": { + "note": "Caffeine can bring out the natural stimulation from psychedelic drugs to make it uncomfortable. High doses can cause anxiety which is hard to handle while tripping", + "status": "Caution" + }, + "nitrous": { + "status": "Low Risk & No Synergy" + }, + "opioids": { + "status": "Low Risk & No Synergy" + }, + "pcp": { + "note": "Details of this combination are not well understood but PCP generally interacts in an unpredictable manner.", + "status": "Caution" + }, + "pregabalin": { + "note": "There is a risk of seizures from this combination, especially at higher dosages. Caffeine additionally reduces pregabalin’s anticonvulsant effects found in lower dosages. Caffeine increases respiration rate allowing for a higher dose of sedatives than normal. If amphetamines wears off first, recreational dosages of pregabalin may overcome the individual and cause respiratory arrest. Both substances at recreational dosages cause strain of the heart and may lead to further dangerous heart complications. Medical dosages are unlikely to be of concern.", + "sources": [ + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben‐Menachem, E. (2004)", + "title": "Pregabalin Pharmacology and Its Relevance to Clinical Practice. Epilepsia, 45(s6), 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Chwedorowicz, R., Łukawski, K., Raszewski, G., & Czuczwar, S. J. (2022)", + "title": "Effect of caffeine on the anticonvulsant action of pregabalin against electroconvulsions in mice. Pharmacological Reports: PR, 74(2), 431–437.", + "url": "https://doi.org/10.1007/s43440-022-00356-1" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures: A historical-controlled trial. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N., & Livingston, J. (2006)", + "title": "Aggravation of epilepsy by anti‐epileptic drugs. Developmental Medicine & Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Miziak, B., Błaszczyk, B., Chrościńska-Krawczyk, M., & Czuczwar, S. J. (2023)", + "title": "Caffeine and Its Interactions with Antiseizure Medications—Is There a Correlation between Preclinical and Clinical Data? International Journal of Molecular Sciences, 24(24), 17569.", + "url": "https://doi.org/10.3390/ijms242417569" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + } + ], + "status": "Unsafe" + }, + "ssris": { + "status": "Low Risk & No Synergy" + }, + "tramadol": { + "status": "Low Risk & No Synergy" + } + }, + "cannabis": { + "2c-t-x": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "2c-x": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "5-meo-xxt": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "alcohol": { + "note": "In excess, this combination can cause nausea.", + "status": "Low Risk & Synergy" + }, + "amphetamines": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "amt": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics. Small amounts can reduce nausea with aMT but take care.", + "status": "Caution" + }, + "benzodiazepines": { + "status": "Low Risk & Decrease" + }, + "caffeine": { + "status": "Low Risk & No Synergy" + }, + "cocaine": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "dextromethorphan": { + "status": "Low Risk & Synergy" + }, + "dmt": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "dox": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "ghb/gbl": { + "status": "Low Risk & Synergy" + }, + "ketamine": { + "status": "Low Risk & Synergy" + }, + "lsd": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "maois": { + "status": "Low Risk & Synergy" + }, + "mdma": { + "note": "Large amounts of cannabis may cause strong and somewhat unpredictable experiences in combination with MDMA. Cannabis should be saved for towards the end of the experience if possible.", + "status": "Low Risk & Synergy" + }, + "mescaline": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "mushrooms": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "mxe": { + "status": "Low Risk & Synergy" + }, + "nbomes": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "status": "Low Risk & Synergy" + }, + "pcp": { + "status": "Low Risk & Synergy" + }, + "pregabalin": { + "note": "Both substances may increase each other's side effects, such as sedation, lowered blood pressure, and raised heart rate.", + "sources": [ + { + "author": "Balachandran, P., Elsohly, M., & Hill, K. P.", + "title": "Cannabidiol Interactions with Medications, Illicit Substances, and Alcohol: a Comprehensive Review (2021)", + "url": "https://doi.org/10.1007/s11606-020-06504-8" + }, + { + "author": "Klein, T. A., & Clark, C. S.", + "title": "Therapeutic use of cannabis in the US. The Nurse Practitioner, 47(12) (2022)", + "url": "https://doi.org/10.1097/01.NPR.0000884880.81603.c5" + }, + { + "author": "Lile, J. A., Alcorn, J. L., Hays, L. R., Kelly, T. H., Stoops, W. W., Wesley, M. J., & Westgate, P. M.", + "title": "Influence of Pregabalin Maintenance on Cannabis Effects and Related Behaviors in Daily Cannabis Users. Experimental and Clinical Psychopharmacology, 30(5) (2022)", + "url": "https://doi.org/10.1037/pha0000464" + }, + { + "author": "Vázquez, M., Guevara, N., Maldonado, C., Guido, P. C., & Schaiquevich, P.", + "title": "Potential Pharmacokinetic Drug‐Drug Interactions between Cannabinoids and Drugs Used for Chronic Pain (2020)", + "url": "https://doi.org/10.1155/2020/3902740" + } + ], + "status": "Low Risk & Synergy" + }, + "ssris": { + "status": "Low Risk & No Synergy" + }, + "tramadol": { + "status": "Low Risk & Synergy" + } + }, + "cocaine": { + "2c-t-x": { + "note": "Cocaine and 2c-t-x both provide considerable stimulation. When combined they can result in severe vasoconstriction, tachycardia, hypertension, and in extreme cases heart failure.", + "status": "Unsafe" + }, + "2c-x": { + "note": "The anxiogenic and focusing effects of stimulants increase the chance of unpleasant thought loops. The combination is generally unnecessary because of the stimulating effects of psychedelics. Combination of the stimulating effects may be uncomfortable.", + "status": "Caution" + }, + "5-meo-xxt": { + "note": "The anxiogenic and focusing effects of stimulants increase the chance of unpleasant thought loops. The combination is generally unnecessary because of the stimulating effects of psychedelics. ", + "status": "Unsafe" + }, + "alcohol": { + "note": "Cocaine can decrease some of the intoxicating effects of alcohol, causing some people to drink more than they otherwise would, which leads to greater behavioral and physical health risks. There is also some debate about cocaethylene, a metabolite produced when combining alcohol and cocaine, with some researchers positing that it is more cardiotoxic than cocaine on its own. Use moderation when combining these substances.", + "sources": [ + { + "author": "McCance-Katz, E. F., Kosten, T. R., & Jatlow, P. ", + "title": "Concurrent use of cocaine and alcohol is more potent and potentially more toxic than use of either alone—A multiple-dose study.", + "url": "https://doi.org/10.1016/S0006-3223(97)00426-5" + }, + { + "author": "Pergolizzi, J., Breve, F., Magnusson, P., LeQuang, J. A. K., & Varrassi, G.", + "title": "Cocaethylene: When cocaine and alcohol are taken together. (2022)", + "url": "https://doi.org/10.7759/cureus.22498" + }, + { + "author": "Shastry, S., Manoochehri, O., Richardson, L. D., & Manini, A. F. ", + "title": "Cocaethylene cardiotoxicity in emergency department patients with acute drug overdose.", + "url": "https://doi.org/10.1111/acem.14584" + }, + { + "author": "Wiener, S. E., Sutijono, D., Moon, C. H., Subramanian, R. A., Calaycay, J., Rushbrook, J. I., & Zehtabchi, S.", + "title": "Patients with detectable cocaethylene are more likely to require intensive care unit admission after trauma. ", + "url": "https://doi.org/10.1016/j.ajem.2009.06.014" + } + ], + "status": "Unsafe" + }, + "amphetamines": { + "note": "This combination of stimulants will increase strain on the heart. It is not generally worth it as cocaine has a mild blocking effect on dopamine releasers like amphetamine", + "status": "Caution" + }, + "amt": { + "status": "Dangerous" + }, + "benzodiazepines": { + "status": "Low Risk & Decrease" + }, + "caffeine": { + "note": "Both stimulants, risk of tachycardia, hypertension, and in extreme cases heart failure.", + "status": "Caution" + }, + "cannabis": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "dextromethorphan": { + "note": "Both substances raise heart rate, in extreme cases, panic attacks caused by these drugs have led to more serious heart issues", + "status": "Unsafe" + }, + "diphenhydramine": { + "note": "Stimulants increase respiration rate allowing for a higher dose of sedatives than normal. If cocaine wears off first, recreational dosages of DPH may overcome the individual and cause respiratory arrest. Both substances at recreational dosages strain the heart and may lead to further dangerous heart complications. When taken together, both substances can potentially be more reinforcing and have greater risk of methemoglobinemia when higher dosages of DPH are combined with cocaine.", + "sources": [ + { + "author": "Alanazi, M. Q.", + "title": "Drugs may be Induced Methemoglobinemia. Journal of Hematology & Thromboembolic Diseases, 06(01). (2017)", + "url": "https://doi.org/10.4172/2329-8790.1000270" + }, + { + "author": "Banks, M. L., Andersen, M. L., Murnane, K. S., Meyer, R. C., & Howell, L. L.", + "title": "Behavioral and neurochemical effects of cocaine and diphenhydramine combinations in rhesus monkeys. Psychopharmacology, 205(3), 467–474. (2009)", + "url": "https://doi.org/10.1007/s00213-009-1555-y" + }, + { + "author": "chrisn", + "title": "Diphenhydramine [Online post]. Drug-Forum. (2021)", + "url": "https://drugs-forum.com/wiki/Diphenhydramine" + }, + { + "author": "Eshmandi, M., Mohamed, A., Khalil, B., & Belhaj, A.", + "title": "Methaemoglobinaemia Associated With Mixed Cocaine and Amphetamine Overdose: A Case Report. Cureus, 16(1), e51748. (2024)", + "url": "https://doi.org/10.7759/cureus.51748" + }, + { + "author": "Karch, S. B. ", + "title": "Diphenhydramine toxicity: comparisons of postmortem findings in diphenhydramine-, cocaine-, and heroin-related deaths. The American Journal of Forensic Medicine and Pathology, 19(2), 143–147. (1998)", + "url": "https://doi.org/10.1097/00000433-199806000-00008" + }, + { + "author": "Pennefather, J. N.", + "title": "The effects pf cocaine and diphenhydramine upon the reactivity of rat vas deferens to supramaximal doses of noradrenaline and of other agonists: The mode of action of cocaine. European Journal of Pharmacology, 35(2), 333–339. (1976)", + "url": "https://doi.org/10.1016/0014-2999(76)90236-3" + }, + { + "author": "Pergolizzi, J. V., Magnusson, P., LeQuang, J. A. K., Breve, F., & Varrassi, G.", + "title": "Cocaine and Cardiotoxicity: A Literature Review. Cureus, 13(4), e14594. (2021)", + "url": "https://doi.org/10.7759/cureus.14594" + }, + { + "author": "Sicari, V., Patel, P., & Zabbo, C. P.", + "title": "Diphenhydramine. In StatPearls. StatPearls Publishing. (2025)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + }, + { + "author": "Tanda, G., Kopajtic, T. A., & Katz, J. L.", + "title": "Cocaine-Like Neurochemical Effects of Antihistaminic Medications. Journal of Neurochemistry, 106(1), 147–157. (2008)", + "url": "https://doi.org/10.1111/j.1471-4159.2008.05361.x" + }, + { + "author": "Wang, Z., & Woolverton, W. L.", + "title": "Self-administration of cocaine-antihistamine combinations: Super-additive reinforcing effects. European Journal of Pharmacology, 557(2–3), 159–160. (2007)", + "url": "https://doi.org/10.1016/j.ejphar.2006.11.056" + }, + { + "author": "Wang, Z., & Woolverton, W. L.", + "title": "Super-additive interaction of the reinforcing effects of cocaine and H1-antihistamines in rhesus monkeys. Pharmacology Biochemistry and Behavior, 91(4), 590–595. (2009)", + "url": "https://doi.org/10.1016/j.pbb.2008.09.013" + }, + { + "author": "Weichert, I.", + "title": "Acute Management of Cocaine-Associated Methaemoglobinaemia. Case Reports in Medicine, 2011, 1–3. (2011)", + "url": "https://doi.org/10.1155/2011/136396" + } + ], + "status": "Caution" + }, + "dmt": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "dox": { + "note": "The combined stimulating effects of the two can lead to an uncomfortable body-load, while the focusing effects of cocaine can easily lead to thought loops. Coming down from cocaine while the DOx is still active can be quite anxiogenic", + "status": "Unsafe" + }, + "ghb/gbl": { + "note": "Stimulants increase respiration rate allowing for a higher dose of sedatives than normal. If the stimulant wears off first the opiate may overcome the individual and cause respiratory arrest. Likewise the ghb/gbl can wear off and leave a dangerous concentration of cocaine behind", + "status": "Caution" + }, + "ketamine": { + "note": "No unexpected interactions, though likely to increase blood pressure but not an issue with sensible doses. Moving around on high doses of this combination may be ill advised due to risk of physical injury.", + "status": "Caution" + }, + "lithium": { + "note": "Lithium may inhibit some of the recreational effects of cocaine.", + "sources": [ + { + "author": "Flemenbaum, A.", + "title": "Antagonism of behavioral effects of cocaine by lithium. (1977)", + "url": "https://doi.org/10.1016/0091-3057(77)90015-6" + }, + { + "author": "Cronson, A. J., & Flemenbaum, A.", + "title": "Antagonism of Cocaine Highs by Lithium. (1981)", + "url": "https://doi.org/10.1007/978-1-4684-3614-3_132" + } + ], + "status": "Low Risk & Decrease" + }, + "lsd": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "maois": { + "note": "This combination is poorly explored", + "status": "Dangerous" + }, + "mdma": { + "note": "Cocaine blocks some of the desirable effects of MDMA while increasing the risk of heart attack.", + "status": "Caution" + }, + "mescaline": { + "note": "The focus and anxiety caused by stimulants is magnified by psychedelics and results in an increased risk of thought loops", + "status": "Caution" + }, + "mushrooms": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "mxe": { + "note": "Stimulants taken with MXE can lead to hypermanic states much more easily, especially if sleep is avoided.", + "status": "Caution" + }, + "nbomes": { + "note": "Cocaine and NBOMes both provide considerable stimulation. When combined they can result in severe vasoconstriction, tachycardia, hypertension, and in extreme cases heart failure.", + "status": "Unsafe" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "note": "Stimulants increase respiration rate allowing for a higher dose of opiates than normal. If the stimulant wears off first then the opiate may overcome the individual and cause respiratory arrest.", + "status": "Dangerous" + }, + "pcp": { + "note": "This combination can easily lead to hypermanic states", + "status": "Unsafe" + }, + "pregabalin": { + "note": "There is a significant risk of seizures from this combination. Stimulants increase respiration rate, allowing for a higher dose of sedatives than normal. If cocaine wears off first, recreational dosages of pregabalin may overcome the individual and cause respiratory arrest. Both substances at recreational dosages strain the heart and may lead to further dangerous heart complications. The combination has a greater risk of methemoglobinemia when higher dosages are combined.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure: Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Hunter, L., Gordge, L., Dargan, P. I., & Wood, D. M. (2011)", + "title": "Methaemoglobinaemia associated with the use of cocaine and volatile nitrites as recreational drugs: a review. British Journal of Clinical Pharmacology, 72(1), 18–26.", + "url": "https://doi.org/10.1111/j.1365-2125.2011.03950.x" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Lappin, J. M., & Sara, G. E. (2019)", + "title": "Psychostimulant use and the brain. Addiction, 114(11), 2065–2077.", + "url": "https://doi.org/10.1111/add.14708" + }, + { + "author": "Ludlow, J. T., Wilkerson, R. G., & Nappe, T. M. (2025)", + "title": "Methemoglobinemia. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK537317/" + }, + { + "author": "Pergolizzi, J. V., Magnusson, P., LeQuang, J. A. K., Breve, F., & Varrassi, G. (n.d.)", + "title": "Cocaine and Cardiotoxicity: A Literature Review. Cureus, 13(4), e14594.", + "url": "https://doi.org/10.7759/cureus.14594" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + } + ], + "status": "Unsafe" + }, + "ssris": { + "note": "May reduce each others' effectiveness. Cocaine can reduce mental stability and therefore exacerbate conditions which SSRIs are used to treat.", + "status": "Low Risk & No Synergy" + }, + "tramadol": { + "note": "Tramadol and stimulants both increase the risk of seizures.", + "status": "Dangerous" + } + }, + "dextromethorphan": { + "2c-t-x": { + "status": "Unsafe" + }, + "2c-x": { + "status": "Low Risk & Synergy" + }, + "5-meo-xxt": { + "note": "Little information exists about this combination.", + "status": "Unsafe" + }, + "alcohol": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place the affected individual in the recovery position to prevent vomit aspiration from excess. Additionally, CNS depression can lead to difficulty breathing. Avoid on anything higher than 1st plateau.", + "status": "Dangerous" + }, + "amphetamines": { + "note": "Both substances raise heart rate, in extreme cases, panic attacks caused by these drugs have led to more serious heart issues.", + "status": "Unsafe" + }, + "amt": { + "status": "Dangerous" + }, + "benzodiazepines": { + "note": "Small doses of benzos can end a bad trip, but both substances potentiate the ataxia and sedation caused by the other and this can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position.", + "status": "Caution" + }, + "caffeine": { + "note": "High doses of caffeine can potentially exacerbate anxiety, especially during a dissociative experience, due to its stimulating effects. This combination might also lead to physical discomfort. However, individual responses to caffeine can vary significantly, often influenced by factors like habitual versus occasional usage.", + "sources": [ + { + "author": "Chad J Reissig, Lawrence P Carter, Matthew W Johnson, Miriam Z Mintzer, Margaret A Klinedinst, Roland R Griffiths", + "title": "High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens ", + "url": "https://pubmed.ncbi.nlm.nih.gov/22526529/" + }, + { + "author": "Arthur Eumann Mesas, Luz M Leon-Muñoz, Fernando Rodriguez-Artalejo, Esther Lopez-Garcia", + "title": "The effect of coffee on blood pressure and cardiovascular disease in hypertensive individuals: a systematic review and meta-analysis ", + "url": "https://pubmed.ncbi.nlm.nih.gov/21880846/" + }, + { + "author": "M-L Nurminen, L Niittynen, R Korpela & H Vapaatalo", + "title": "Coffee, caffeine and blood pressure: a critical review", + "url": "https://www.nature.com/articles/1600899" + } + ], + "status": "Caution" + }, + "cannabis": { + "status": "Low Risk & Synergy" + }, + "cocaine": { + "note": "Both substances raise heart rate, in extreme cases, panic attacks caused by these drugs have led to more serious heart issues", + "status": "Unsafe" + }, + "diphenhydramine": { + "note": "The combination is reported to reduce the side effects of each drug and potentiate many of the recreational effects. There is a significant risk of serotonin syndrome, increased delirium, CNS depression, cognitive inhibition, risk of physical injury, hyperthermia, mania, paranoia, and psychosis, especially at higher dosages. There is an additional concern of tachycardia, hypertension, and in extreme cases, heart failure. Diphenhydramine is reported to inhibit the CYP2D6 enzyme which can increase levels of DXM. Medical dosages are not reported to be a concern. Caution is strongly recommended with this combination.", + "sources": [ + { + "author": "Abdul Manap, Wright, Gregory, Rostami‐Hodjegan, Meller, Kelm, Lennard, Tucker, & Morice. (1999)", + "title": "The antitussive effect of dextromethorphan in relation to CYP2D6 activity. British Journal of Clinical Pharmacology, 48(3), 382–387.", + "url": "https://doi.org/10.1046/j.1365-2125.1999.00029.x" + }, + { + "author": "Akutsu, T., Kobayashi, K., Sakurada, K., Ikegaya, H., Furihata, T., & Chiba, K. (2007)", + "title": "Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 35(1), 72–78.", + "url": "https://doi.org/10.1124/dmd.106.012088" + }, + { + "author": "Clark, J. H., Meltzer, E. O., & Naclerio, R. M. (2025)", + "title": "Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027.", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Crazy Steve. (2004)", + "title": "Mind Expansion: An Experience with DXM & Diphenhydramine (exp33999). Erowid.org.", + "url": "https://www.erowid.org/experiences/exp.php?ID=33999" + }, + { + "author": "De Leon, J., & Nikoloff, D. M. (2008)", + "title": "Paradoxical Excitation on Diphenhydramine May Be Associated with Being a CYP2D6 Ultrarapid Metabolizer: Three Case Reports. CNS Spectrums, 13(2), 133–135.", + "url": "https://doi.org/10.1017/S109285290001628X" + }, + { + "author": "Hamelin, B. (2000a)", + "title": "Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity. Clinical Pharmacology & Therapeutics, 67(5), 466–477.", + "url": "https://doi.org/10.1067/mcp.2000.106464" + }, + { + "author": "HANS. (2022)", + "title": "First Overdose: An Experience with DXM & Diphenhydramine (exp116238). Erowid.org.", + "url": "https://www.erowid.org/experiences/exp.php?ID=116238" + }, + { + "author": "Jun, J. H., Thorndike, E. B., & Schindler, C. W. (2004a)", + "title": "Abuse liability and stimulant properties of dextromethorphan and diphenhydramine combinations in rats. Psychopharmacology, 172(3), 277–282.", + "url": "https://doi.org/10.1007/s00213-003-1650-4" + }, + { + "author": "Josie Kins", + "title": "The DXM and DPH combination, broken down and described", + "url": "https://disregardeverythingisay.com/post/39670297758/the-dxm-and-dph-combination-broken-down-and" + }, + { + "author": "Lessard, E., Yessine, M. A., Hamelin, B. A., Gauvin, C., Labbé, L., O’Hara, G., LeBlanc, J., & Turgeon, J. (2001)", + "title": "Diphenhydramine alters the disposition of venlafaxine through inhibition of CYP2D6 activity in humans. Journal of Clinical Psychopharmacology, 21(2), 175–184.", + "url": "https://doi.org/10.1097/00004714-200104000-00009" + }, + { + "author": "Psychonaut Wiki", + "title": "DXM & DPH", + "url": "https://psychonautwiki.org/wiki/DXM_%26_DPH" + }, + { + "author": "Romanelli, F., & Smith, K. M. (2009)", + "title": "Dextromethorphan abuse: Clinical effects and management. Journal of the American Pharmacists Association, 49(2), e20–e27.", + "url": "https://doi.org/10.1331/JAPhA.2009.08091" + }, + { + "author": "Schwartz, A. R., Pizon, A. F., & Brooks, D. E. (2008)", + "title": "Dextromethorphan-induced serotonin syndrome. Clinical Toxicology, 46(8), 771–773.", + "url": "https://doi.org/10.1080/15563650701668625" + }, + { + "author": "The Salvia Shaman. (2025)", + "title": "Delirium Visions and Teleportation: An Experience with DXM & Diphenhydramine (exp113902). Erowid.org.", + "url": "https://www.erowid.org/experiences/exp.php?ID=113902" + }, + { + "author": "u/syrup_ben_goed (n.d.)", + "title": "The \"right way\" to do DXM + DPH combo, from an experienced user", + "url": "https://www.reddit.com/r/Drugs/comments/ajlupr/the_right_way_to_do_dxm_dph_comb" + } + ], + "status": "Unsafe" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "dox": { + "note": "The DOx class as psychedelic stimulants have the potential to mask the effects of DXM and could lead to redosing to an unsafe level. DXM can also potentiate DOx resulting in an unpleasantly intense experience.", + "status": "Unsafe" + }, + "ghb/gbl": { + "note": "Both substances cause ataxia and bring a risk of vomiting and unconsciousness. If the individual falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position. This combination is hard to predict", + "status": "Dangerous" + }, + "ketamine": { + "note": "Both substances primarily exert their effects through NMDA antagonism. Currently, there is no evidence regarding mechanisms that might reduce these effects.", + "sources": [ + { + "author": "Jeanna M. Marraffa", + "title": "Dextromethorphan", + "url": "https://doi.org/10.1016/B978-0-12-824315-2.00127-5" + }, + { + "author": "Georges Mion, Thierry Villevieille", + "title": "Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings)", + "url": "https://doi.org/10.1111/cns.12099" + }, + { + "author": "P. Klepstad, P. C. Borchgrevink", + "title": "Four years' treatment with ketamine and a trial of dextromethorphan in a patient with severe post-herpetic neuralgia", + "url": "https://doi.org/10.1111/j.1399-6576.1997.tb04709.x" + }, + { + "author": "Stephen M. Stahl", + "title": "Mechanism of action of dextromethorphan/quinidine: comparison with ketamine", + "url": "https://doi.org/10.1017/S109285291300062X" + }, + { + "author": "A M Hughes,1 J Rhodes,1 G Fisher,2 M Sellers,3 and J W Growcott1", + "title": "Assessment of the effect of dextromethorphan and ketamine on the acute nociceptive threshold and wind-up of the second pain response in healthy male volunteers", + "url": "https://doi.org/10.1046%2Fj.1365-2125.2002.01602.x" + }, + { + "author": "Keiji Tabuchi, MD, Zenya Ito, MD, Shigeki Tsuji, MD, Akira Hara, MD, Tetsuro Wada, MD, Jun Kusakari, MD", + "title": "Effect of Ketamine, Dextromethorphan, and MK-801 on Cochlear Dysfunction Induced by Transient Ischemia", + "url": "https://doi.org/10.1177/000348940211100107" + } + ], + "status": "Low Risk & Synergy" + }, + "lithium": { + "note": "There is a risk of serotonin syndrome when combining Lithium with DXM.", + "sources": [ + { + "author": "Lenox, R. H., & Hahn, C. G.", + "title": "Overview of the mechanism of action of lithium in the brain: fifty-year update (2000)", + "url": "https://pubmed.ncbi.nlm.nih.gov/10826655/" + }, + { + "author": "Shahani, L.", + "title": "Venlafaxine Augmentation With Lithium Leading to Serotonin Syndrome (2012)", + "url": "https://doi.org/10.1176/appi.neuropsych.11080196" + }, + { + "author": "DeBattista, C., Sofuoglu, M., & Schatzberg, A. F.", + "title": "Serotonergic synergism: the risks and benefits of combining the selective serotonin reuptake inhibitors with other serotonergic drugs (1998)", + "url": "https://doi.org/10.1016/s0006-3223(98)00161-9" + }, + { + "author": "Massot, O.", + "title": "5-HT1B Receptors: A Novel Target for Lithium: Possible Involvement in Mood Disorders (1999)", + "url": "https://doi.org/10.1016/S0893-133X(99)00042-1" + }, + { + "author": "Navarro, A., Perry, C., & Bobo, W. V.", + "title": "A case of serotonin syndrome precipitated by abuse of the anticough remedy dextromethorphan in a bipolar patient treated with fluoxetine and lithium. (2006)", + "url": "https://doi.org/10.1016/j.genhosppsych.2005.06.008" + } + ], + "status": "Dangerous" + }, + "lsd": { + "status": "Low Risk & Synergy" + }, + "maois": { + "note": "High risk of serotonin syndrome", + "status": "Dangerous" + }, + "mdma": { + "status": "Dangerous" + }, + "mephedrone": { + "note": "Risk of serotonin syndrome as both drugs raise serotonin levels. In addition to concerns of high blood pressure and unnecessary strain on the heart. As well as potentially causing anxiety and greater physical discomfort due to the combination.", + "sources": [ + { + "author": "J Kehr, F Ichinose, S Yoshitake, M Goiny, T Sievertsson, F Nyberg, T Yoshitake", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Gregory C. Hadlock, Katy M. Webb, Lisa M. McFadden, Pei Wen Chu, Jonathan D. Ellis, Scott C. Allen, David M. Andrenyak, Paula L. Vieira-Brock, Christopher L. German, Kevin M. Conrad, Amanda J. Hoonakker, James W. Gibb, Diana G. Wilkins, Glen R. Hanson and Annette E. Fleckenstein", + "title": "4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse", + "url": "https://doi.org/10.1124/jpet.111.184119 " + }, + { + "author": "Anna R. Schwartz, Anthony F. Pizon & Daniel E. Brooks", + "title": "Dextromethorphan-induced serotonin syndrome", + "url": "https://doi.org/10.1080/15563650701668625" + }, + { + "author": "DrugBank", + "title": "Dextromethorphan", + "url": "https://go.drugbank.com/drugs/DB00514" + }, + { + "author": "Henderson MG, Fuller RW", + "title": "Dextromethorphan antagonizes the acute depletion of brain serotonin by p-chloroamphetamine and H75/12 in rats", + "url": "https://doi.org/10.1016/0006-8993(92)91144-4" + }, + { + "author": "Reissig CJ, Carter LP, Johnson MW, Mintzer MZ, Klinedinst MA, Griffiths RR", + "title": "High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens ", + "url": "https://doi.org/10.1007/s00213-012-2680-6" + }, + { + "author": "Meng H, Cao J, Kang J, Ying X, Ji J, Reynolds W, Rampe D.", + "title": "Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat ", + "url": "https://doi.org/10.1016/j.toxlet.2011.10.010" + } + ], + "status": "Dangerous" + }, + "mescaline": { + "status": "Low Risk & Synergy" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "note": "There is a risk of serotonin syndrome when combining DXM with MXE, due to DXM and MXE both being SRI’s. MXE and DXM having notable affinities for the serotonin transporter.", + "sources": [ + { + "author": "Bryan L. Roth, Simon Gibbons, Warunya Arunotayanun, Xi-Ping Huang, Vincent Setola, Ric Treble, Les Iversen", + "title": "The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor", + "url": "https://doi.org/10.1371/journal.pone.0059334" + }, + { + "author": "Matteo Marti, Giuseppe Talani, Cristina Miliano, Sabrine Bilel, Francesca Biggio, Jessica Bratzu, Marco Diana, Maria Antonietta De Luca, Liana Fattore", + "title": "New insights into methoxetamine mechanisms of action: Focus on serotonergic 5-HT2 receptors in pharmacological and behavioral effects in the rat ", + "url": "https://doi.org/10.1016/j.expneurol.2021.113836" + }, + { + "author": "Laura Hondebrink, Emma E.J. Kasteel, Anke M. Tukker, Fiona M.J. Wijnolts, Anouk H.A. Verboven, Remco H.S. Westerink", + "title": "Neuropharmacological characterization of the new psychoactive substance methoxetamine", + "url": "https://doi.org/10.1016/j.neuropharm.2017.04.035" + }, + { + "author": "Linda L. Werling, Ashleigh Keller, Julie G. Frank, Samer J. Nuwayhid", + "title": "A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: Treatment of involuntary emotional expression disorder", + "url": "https://doi.org/10.1016/j.expneurol.2007.06.013" + }, + { + "author": "Linda Nguyen, Kelan L. Thomas, Brandon P. Lucke-Wold, John Z. Cavendish, Molly S. Crowe, Rae R. Matsumoto", + "title": "Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders", + "url": "https://doi.org/10.1016/j.pharmthera.2016.01.016" + } + ], + "status": "Unsafe" + }, + "nbomes": { + "status": "Unsafe" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "note": "CNS depression, difficult breathing, heart issues, hepatoxic, just very unsafe combination all around. Additionally if one takes DXM, their tolerance of opiates goes down slightly, thus causing additional synergistic effects.", + "status": "Dangerous" + }, + "pcp": { + "status": "Dangerous" + }, + "pregabalin": { + "note": "Pregabalin and DXM may increase each other’s effects such as inhibition, dizziness, sedation. At higher doses this can lead to unexpected loss of consciousness. Both drugs have seizure concerns which is greatly increased in combination.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Journey, J. D., Agrawal, S., & Stern, E. (2025)", + "title": "Dextromethorphan Toxicity. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK538502/" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Oh, S., Agrawal, S., Sabir, S., & Taylor, A. (2025)", + "title": "Dextromethorphan. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK538216/" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + } + ], + "status": "Unsafe" + }, + "ssris": { + "note": "High risk of serotonin syndrome.", + "status": "Dangerous" + }, + "tramadol": { + "status": "Dangerous" + } + }, + "diphenhydramine": { + "alcohol": { + "note": "The two substances potentiate each other strongly and unpredictably, and may rapidly lead to unconsciousness. They both increase each other's side effects such as ataxia, sedation, and CNS depression. Blackouts and memory loss are significantly increased. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position. Alcohol may also increase the deliriant effects of diphenhydramine. It should also be noted if the individual consuming alcohol typically has a flushing response to alcohol, diphenhydramine may reduce the reaction and mask some of the effects of the alcohol.", + "sources": [ + { + "author": "ScienceDirect", + "title": "Diphenhydramine - an overview (2024)", + "url": "https://www.sciencedirect.com/topics/chemistry/diphenhydramine" + }, + { + "author": "ScienceDirect", + "title": "Ethanol - an overview (2024)", + "url": "https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/ethanol" + }, + { + "author": "Miller, N. S., Goodwin, D. W., Jones, F. C., Gabrielli, W. F., Pardo, M. P., Anand, M. M., & Hall, T. B.", + "title": "Antihistamine blockade of alcohol-induced flushing in orientals. Journal of Studies on Alcohol, 49(1), 16-20 (1988)", + "url": "https://doi.org/10.15288/jsa.1988.49.16" + }, + { + "author": "Sicari, V., & Zabbo, C. P.", + "title": "Diphenhydramine. In StatPearls. StatPearls Publishing (2024)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + }, + { + "author": "Weathermon, R., & Crabb, D. W.", + "title": "Alcohol and Medication Interactions. Alcohol Research & Health, 23(1), 40-54 (1999)", + "url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761694/" + } + ], + "status": "Dangerous" + }, + "amphetamines": { + "note": "Amphetamines as a stimulant may mask some of the negative side effects of DPH, leading to delusions of sobriety which has additional concern in states of delirium. The combination of stimulants will increase strain on the heart and may cause some physical discomfort, and has the chance to cause life-threatening cardiovascular issues. The combination may also increase each other's neurotoxicity at higher dosages. The combination may increase anxiety levels and risks of thought loops on higher dosages, in addition to increasing each others negative side effects. Medical and common dosages of each substances are reported to not be a concern. Additionally, it is suggested that DPH potentiates amphetamine psychomotor activation, in addition to other interactions such as potentiation through inhibition of CYP2D6 and histamine H1 and H2 receptors, among other alterations.", + "sources": [ + { + "author": "Berman, S. M.; Kuczenski, R.; McCracken, J. T.; London, E. D.", + "title": "Potential adverse effects of amphetamine treatment on brain and behavior: a review. Molecular Psychiatry, 14(2), 123–142 (2009)", + "url": "https://doi.org/10.1038/mp.2008.90" + }, + { + "author": "Clark, J. H.; Meltzer, E. O.; Naclerio, R. M.", + "title": "Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027 (2025)", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Martin, D.; Le, J. K.", + "title": "Amphetamine. In StatPearls. StatPearls Publishing (2025)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK556103/" + }, + { + "author": "McAtee, K. J.; Brillhart, D.; Barbuto, A. F.; Hiller, H. M.", + "title": "Wide complex tachycardia secondary to massive diphenhydramine overdose: a case report. Journal of Emergency and Critical Care Medicine, 6 (2022)", + "url": "https://doi.org/10.21037/jeccm-21-33" + }, + { + "author": "Mohs, R. C.; Tinklenberg, J. R.; Roth, W. T.; Kopell, B. S.", + "title": "Methamphetamine and diphenhydramine effects on the rate of cognitive processing. Psychopharmacology (1978)", + "url": "https://doi.org/10.1007/BF00428024" + }, + { + "author": "Okuda, T.; Ito, Y.; Nakagawa, N.; Hishinuma, T.; Tsukamoto, H.; Iwabuchi, K.; Watanabe, T.; Kitaichi, K.; Goto, J.; Yanai, K.", + "title": "Drug interaction between methamphetamine and antihistamines: behavioral changes and tissue concentrations of methamphetamine in rats. European Journal of Pharmacology, 505(1), 135–144 (2004)", + "url": "https://doi.org/10.1016/j.ejphar.2004.10.022" + }, + { + "author": "Sicari, V.; Patel, P.; Zabbo, C. P.", + "title": "Diphenhydramine. In StatPearls. StatPearls Publishing (2025)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + }, + { + "author": "Steinkellner, T.; Freissmuth, M.; Sitte, H. H.; Montgomery, T.", + "title": "The ugly side of amphetamines: short- and long-term toxicity of MDMA, methamphetamine and d-amphetamine. Biological Chemistry, 392(0) (2011)", + "url": "https://doi.org/10.1515/BC.2011.016" + }, + { + "author": "Vasan, S.; Murray, B. P.; Olango, G. J.", + "title": "Amphetamine Toxicity. In StatPearls. StatPearls Publishing (2025)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK470276/" + } + ], + "status": "Caution" + }, + "benzodiazepines": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are likely. Low medical doses are unlikely to be of concern.", + "sources": [ + { + "author": "Bounds, Connor G., and Preeti Patel. (2025)", + "title": "Benzodiazepines. StatPearls, StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK470159/" + }, + { + "author": "Montoro, J., et al. (2013)", + "title": "H1 Antihistamines and Benzodiazepines. Pharmacological Interactions and Their Impact on Cerebral Function. Journal of Investigational Allergology & Clinical Immunology, 23 Suppl 1, 17–26.", + "url": "https://pubmed.ncbi.nlm.nih.gov/24672891/" + }, + { + "author": "Sicari, Vincent, et al. (2025)", + "title": "Diphenhydramine. StatPearls, StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + } + ], + "status": "Unsafe" + }, + "caffeine": { + "note": "Caffeine as a stimulant may mask some negative side effects of DPH, leading to delusions of sobriety, which has additional concerns in states of delirium. The combination of stimulants will increase strain on the heart and may cause some physical discomfort, and has the chance to cause cardiovascular issues such as complex tachycardia. The combination may increase anxiety levels and risks of thought loops at higher dosages, in addition to increasing each other's negative side effects. Medical dosages are reported to not be a concern.", + "sources": [ + { + "author": "Clark, J. H.; Meltzer, E. O.; Naclerio, R. M. (2025)", + "title": "Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027.", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Evans, J.; Richards, J. R.; Battisti, A. S. (2025)", + "title": "Caffeine. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK519490/" + }, + { + "author": "McAtee, K. J.; Brillhart, D.; Barbuto, A. F.; Hiller, H. M. (2022)", + "title": "Wide complex tachycardia secondary to massive diphenhydramine overdose: a case report. Journal of Emergency and Critical Care Medicine, 6(0).", + "url": "https://doi.org/10.21037/jeccm-21-33" + }, + { + "author": "Murray, A.; Traylor, J. (2025)", + "title": "Caffeine Toxicity. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK532910/" + }, + { + "author": "Institute of Medicine (US) Committee on Military Nutrition Research (2001)", + "title": "Pharmacology of Caffeine. In Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations. National Academies Press (US).", + "url": "https://www.ncbi.nlm.nih.gov/books/NBK223808/" + }, + { + "author": "Sicari, V.; Patel, P.; Zabbo, C. P. (2025)", + "title": "Diphenhydramine. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + }, + { + "author": "Tharion, W. J.; Kobrick, J. L.; Lieberman, H. R.; Fine, B. J. (1993)", + "title": "Effects of caffeine and diphenhydramine on auditory evoked cortical potentials. Perceptual and Motor Skills, 76(3 Pt 1), 707–715.", + "url": "https://doi.org/10.2466/pms.1993.76.3.707" + } + ], + "status": "Caution" + }, + "cocaine": { + "note": "Stimulants increase respiration rate allowing for a higher dose of sedatives than normal. If cocaine wears off first, recreational dosages of DPH may overcome the individual and cause respiratory arrest. Both substances at recreational dosages strain the heart and may lead to further dangerous heart complications. When taken together, both substances can potentially be more reinforcing and have greater risk of methemoglobinemia when higher dosages of DPH are combined with cocaine.", + "sources": [ + { + "author": "Alanazi, M. Q.", + "title": "Drugs may be Induced Methemoglobinemia. Journal of Hematology & Thromboembolic Diseases, 06(01). (2017)", + "url": "https://doi.org/10.4172/2329-8790.1000270" + }, + { + "author": "Banks, M. L., Andersen, M. L., Murnane, K. S., Meyer, R. C., & Howell, L. L.", + "title": "Behavioral and neurochemical effects of cocaine and diphenhydramine combinations in rhesus monkeys. Psychopharmacology, 205(3), 467–474. (2009)", + "url": "https://doi.org/10.1007/s00213-009-1555-y" + }, + { + "author": "chrisn", + "title": "Diphenhydramine [Online post]. Drug-Forum. (2021)", + "url": "https://drugs-forum.com/wiki/Diphenhydramine" + }, + { + "author": "Eshmandi, M., Mohamed, A., Khalil, B., & Belhaj, A.", + "title": "Methaemoglobinaemia Associated With Mixed Cocaine and Amphetamine Overdose: A Case Report. Cureus, 16(1), e51748. (2024)", + "url": "https://doi.org/10.7759/cureus.51748" + }, + { + "author": "Karch, S. B. ", + "title": "Diphenhydramine toxicity: comparisons of postmortem findings in diphenhydramine-, cocaine-, and heroin-related deaths. The American Journal of Forensic Medicine and Pathology, 19(2), 143–147. (1998)", + "url": "https://doi.org/10.1097/00000433-199806000-00008" + }, + { + "author": "Pennefather, J. N.", + "title": "The effects pf cocaine and diphenhydramine upon the reactivity of rat vas deferens to supramaximal doses of noradrenaline and of other agonists: The mode of action of cocaine. European Journal of Pharmacology, 35(2), 333–339. (1976)", + "url": "https://doi.org/10.1016/0014-2999(76)90236-3" + }, + { + "author": "Pergolizzi, J. V., Magnusson, P., LeQuang, J. A. K., Breve, F., & Varrassi, G.", + "title": "Cocaine and Cardiotoxicity: A Literature Review. Cureus, 13(4), e14594. (2021)", + "url": "https://doi.org/10.7759/cureus.14594" + }, + { + "author": "Sicari, V., Patel, P., & Zabbo, C. P.", + "title": "Diphenhydramine. In StatPearls. StatPearls Publishing. (2025)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + }, + { + "author": "Tanda, G., Kopajtic, T. A., & Katz, J. L.", + "title": "Cocaine-Like Neurochemical Effects of Antihistaminic Medications. Journal of Neurochemistry, 106(1), 147–157. (2008)", + "url": "https://doi.org/10.1111/j.1471-4159.2008.05361.x" + }, + { + "author": "Wang, Z., & Woolverton, W. L.", + "title": "Self-administration of cocaine-antihistamine combinations: Super-additive reinforcing effects. European Journal of Pharmacology, 557(2–3), 159–160. (2007)", + "url": "https://doi.org/10.1016/j.ejphar.2006.11.056" + }, + { + "author": "Wang, Z., & Woolverton, W. L.", + "title": "Super-additive interaction of the reinforcing effects of cocaine and H1-antihistamines in rhesus monkeys. Pharmacology Biochemistry and Behavior, 91(4), 590–595. (2009)", + "url": "https://doi.org/10.1016/j.pbb.2008.09.013" + }, + { + "author": "Weichert, I.", + "title": "Acute Management of Cocaine-Associated Methaemoglobinaemia. Case Reports in Medicine, 2011, 1–3. (2011)", + "url": "https://doi.org/10.1155/2011/136396" + } + ], + "status": "Caution" + }, + "dextromethorphan": { + "note": "The combination is reported to reduce the side effects of each drug and potentiate many of the recreational effects. There is a significant risk of serotonin syndrome, increased delirium, CNS depression, cognitive inhibition, risk of physical injury, hyperthermia, mania, paranoia, and psychosis, especially at higher dosages. There is an additional concern of tachycardia, hypertension, and in extreme cases, heart failure. Diphenhydramine is reported to inhibit the CYP2D6 enzyme which can increase levels of DXM. Medical dosages are not reported to be a concern. Caution is strongly recommended with this combination.", + "sources": [ + { + "author": "Abdul Manap, Wright, Gregory, Rostami‐Hodjegan, Meller, Kelm, Lennard, Tucker, & Morice. (1999)", + "title": "The antitussive effect of dextromethorphan in relation to CYP2D6 activity. British Journal of Clinical Pharmacology, 48(3), 382–387.", + "url": "https://doi.org/10.1046/j.1365-2125.1999.00029.x" + }, + { + "author": "Akutsu, T., Kobayashi, K., Sakurada, K., Ikegaya, H., Furihata, T., & Chiba, K. (2007)", + "title": "Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 35(1), 72–78.", + "url": "https://doi.org/10.1124/dmd.106.012088" + }, + { + "author": "Clark, J. H., Meltzer, E. O., & Naclerio, R. M. (2025)", + "title": "Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027.", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Crazy Steve. (2004)", + "title": "Mind Expansion: An Experience with DXM & Diphenhydramine (exp33999). Erowid.org.", + "url": "https://www.erowid.org/experiences/exp.php?ID=33999" + }, + { + "author": "De Leon, J., & Nikoloff, D. M. (2008)", + "title": "Paradoxical Excitation on Diphenhydramine May Be Associated with Being a CYP2D6 Ultrarapid Metabolizer: Three Case Reports. CNS Spectrums, 13(2), 133–135.", + "url": "https://doi.org/10.1017/S109285290001628X" + }, + { + "author": "Hamelin, B. (2000a)", + "title": "Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity. Clinical Pharmacology & Therapeutics, 67(5), 466–477.", + "url": "https://doi.org/10.1067/mcp.2000.106464" + }, + { + "author": "HANS. (2022)", + "title": "First Overdose: An Experience with DXM & Diphenhydramine (exp116238). Erowid.org.", + "url": "https://www.erowid.org/experiences/exp.php?ID=116238" + }, + { + "author": "Jun, J. H., Thorndike, E. B., & Schindler, C. W. (2004a)", + "title": "Abuse liability and stimulant properties of dextromethorphan and diphenhydramine combinations in rats. Psychopharmacology, 172(3), 277–282.", + "url": "https://doi.org/10.1007/s00213-003-1650-4" + }, + { + "author": "Josie Kins", + "title": "The DXM and DPH combination, broken down and described", + "url": "https://disregardeverythingisay.com/post/39670297758/the-dxm-and-dph-combination-broken-down-and" + }, + { + "author": "Lessard, E., Yessine, M. A., Hamelin, B. A., Gauvin, C., Labbé, L., O’Hara, G., LeBlanc, J., & Turgeon, J. (2001)", + "title": "Diphenhydramine alters the disposition of venlafaxine through inhibition of CYP2D6 activity in humans. Journal of Clinical Psychopharmacology, 21(2), 175–184.", + "url": "https://doi.org/10.1097/00004714-200104000-00009" + }, + { + "author": "Psychonaut Wiki", + "title": "DXM & DPH", + "url": "https://psychonautwiki.org/wiki/DXM_%26_DPH" + }, + { + "author": "Romanelli, F., & Smith, K. M. (2009)", + "title": "Dextromethorphan abuse: Clinical effects and management. Journal of the American Pharmacists Association, 49(2), e20–e27.", + "url": "https://doi.org/10.1331/JAPhA.2009.08091" + }, + { + "author": "Schwartz, A. R., Pizon, A. F., & Brooks, D. E. (2008)", + "title": "Dextromethorphan-induced serotonin syndrome. Clinical Toxicology, 46(8), 771–773.", + "url": "https://doi.org/10.1080/15563650701668625" + }, + { + "author": "The Salvia Shaman. (2025)", + "title": "Delirium Visions and Teleportation: An Experience with DXM & Diphenhydramine (exp113902). Erowid.org.", + "url": "https://www.erowid.org/experiences/exp.php?ID=113902" + }, + { + "author": "u/syrup_ben_goed (n.d.)", + "title": "The \"right way\" to do DXM + DPH combo, from an experienced user", + "url": "https://www.reddit.com/r/Drugs/comments/ajlupr/the_right_way_to_do_dxm_dph_comb" + } + ], + "status": "Unsafe" + }, + "dmt": { + "note": "At 25-50mg, DPH may assist with side effects of the DMT such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and DMT is cautioned against. DMT is likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma.", + "sources": [ + { + "author": "Carbonaro, T. M., & Gatch, M. B. (2016)", + "title": "Neuropharmacology of N,N-Dimethyltryptamine. Brain Research Bulletin, 126(Pt 1), 74–88.", + "url": "https://doi.org/10.1016/j.brainresbull.2016.04.016" + }, + { + "author": "Chapy, H., Smirnova, M., André, P., Schlatter, J., Chiadmi, F., Couraud, P.-O., Scherrmann, J.-M., Declèves, X., & Cisternino, S. (2014)", + "title": "Carrier-Mediated Cocaine Transport at the Blood-Brain Barrier as a Putative Mechanism in Addiction Liability. International Journal of Neuropsychopharmacology, 18(1), pyu001.", + "url": "https://doi.org/10.1093/ijnp/pyu001" + }, + { + "author": "Schaefer, T. S., Patel, P., & Zito, P. M. (2025)", + "title": "Antiemetic Histamine H1 Receptor Blockers. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK533003/" + }, + { + "author": "Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)", + "title": "Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.", + "url": "https://doi.org/10.3389/fpsyt.2021.657397" + }, + { + "author": "Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)", + "title": "Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.", + "url": "https://doi.org/10.1016/j.jaip.2022.07.018" + } + ], + "status": "Caution" + }, + "dox": { + "note": "At 25-50mg, DPH may assist with side effects of DOx drugs such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and DOx drugs is cautioned against. DOx drugs are likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma. DOx drugs and DPH at recreational dosages have additional cardiac concerns such as vasoconstriction, tachycardia, hypertension, which in combination may be exacerbated.", + "sources": [ + { + "author": "ScienceDirect Topics (n.d.)", + "title": "2,5-Dimethoxy-4-iodoamphetamine - an overview", + "url": "https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/2-5-dimethoxy-4-iodoamphetamine" + }, + { + "author": "Barnett, R. Y., Baker, D. D., Kelly, N. E., McGuire, C. E., Fassette, T. C., & Gorniak, J. M. (2014)", + "title": "A Fatal Intoxication of 2,5-Dimethoxy-4-Chloroamphetamine: A Case Report. Journal of Analytical Toxicology, 38(8), 589–591.", + "url": "https://doi.org/10.1093/jat/bku087" + }, + { + "author": "Burish, M. J., Thoren, K. L., Madou, M., Toossi, S., & Shah, M. (2015)", + "title": "Hallucinogens Causing Seizures? A Case Report of the Synthetic Amphetamine 2,5-Dimethoxy-4-Chloroamphetamine. The Neurohospitalist, 5(1), 32–34.", + "url": "https://doi.org/10.1177/1941874414528939" + }, + { + "author": "Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)", + "title": "Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.", + "url": "https://doi.org/10.3389/fpsyt.2021.657397" + }, + { + "author": "Trout, K., & Daley, P. F. (2024)", + "title": "The origin of 2,5‐dimethoxy‐4‐methylamphetamine (DOM, STP). Drug Testing and Analysis, 16(12), 1496–1508.", + "url": "https://doi.org/10.1002/dta.3667" + }, + { + "author": "Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)", + "title": "Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.", + "url": "https://doi.org/10.1016/j.jaip.2022.07.018" + } + ], + "status": "Caution" + }, + "ghb/gbl": { + "note": "Both substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and unconsciousness. The interaction will cause greater inhibition and risk of injury. If the user falls unconscious it is strongly recommended to put them into the recovery position and monitor breathing.", + "sources": [ + { + "author": "William J Tharion, Donna J. McMenemy, Terry M. Rauch", + "title": "Antihistamine Effects on the Central Nervous System, Cognitive Performance and Subjective States. ", + "url": "https://doi.org/10.1159/000119069" + }, + { + "author": "Sicari V, Zabbo CP. Diphenhydramine.", + "title": "Diphenhydramine", + "url": "https://www.ncbi.nlm.nih.gov/books/NBK526010/" + }, + { + "author": "Couper FJ, Marinetti LJ.", + "title": "γ-Hydroxybutyrate (GHB) - Effects on Human Performance and Behavior ", + "url": "https://pubmed.ncbi.nlm.nih.gov/26256488/" + }, + { + "author": "Busardò FP, Jones AW.", + "title": "GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome", + "url": "https://doi.org/10.2174%2F1570159X13666141210215423" + } + ], + "status": "Dangerous" + }, + "ketamine": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Ketamine has a high likelihood of increasing DPH's deliriant effects at higher dosages and can greatly increase the risk of injury, mania, and psychosis. Medical dosages of both substances are unlikely to cause concern.", + "sources": [ + { + "author": "Bylund, W., Delahanty, L., & Cooper, M.", + "title": "The Case of Ketamine Allergy. Clinical Practice and Cases in Emergency Medicine, 1(4), 323–325. (2017)", + "url": "https://doi.org/10.5811/cpcem.2017.7.34405" + }, + { + "author": "Clark, J. H., Meltzer, E. O., & Naclerio, R. M.", + "title": "Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027. (2025)", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Rosenbaum, S. B., Gupta, V., Patel, P., & Palacios, J. L.", + "title": "Ketamine. In StatPearls. StatPearls Publishing. (2025)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK470357/" + }, + { + "author": "Sicari, V., Patel, P., & Zabbo, C. P.", + "title": "Diphenhydramine. In StatPearls. StatPearls Publishing. (2025)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + } + ], + "status": "Dangerous" + }, + "lithium": { + "note": "There is a concern of serotonin syndrome at higher dosages of this combination. Caution is recommended in restricting diphenhydramine to medical dosages (25-50mg). Lithium and diphenhydramine both have concerns of QT prolongation which may be increased when taken in combination; risks increase due to a variety of factors such as the health of the user and drug dosages. Additionally, the combination may increase each drug's side effects, such as dizziness and loss of consciousness.", + "sources": [ + { + "author": "Clark, J. H., Meltzer, E. O., & Naclerio, R. M.", + "title": "Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027. (2025)", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Crouch, M. A., Limon, L., & Cassano, A. T.", + "title": "Clinical Relevance and Management of Drug‐Related QT Interval Prolongation. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 23(7), 881–908. (2003)", + "url": "https://doi.org/10.1592/phco.23.7.881.32730" + }, + { + "author": "Farzam, K., & Tivakaran, V. S.", + "title": "QT Prolonging Drugs. In StatPearls. StatPearls Publishing. (2025)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK534864/" + }, + { + "author": "Finley, P. R.", + "title": "Drug Interactions with Lithium: An Update. Clinical Pharmacokinetics, 55(8), 925–941. (2016)", + "url": "https://doi.org/10.1007/s40262-016-0370-y" + }, + { + "author": "Hawley, C. J., Loughlin, P. J., Quick, S. J., Gale, T. M., Sivakumaran, T., Hayes, J., & McPhee, S.", + "title": "Efficacy, safety and tolerability of combined administration of lithium and selective serotonin reuptake inhibitors: a review of the current evidence. International Clinical Psychopharmacology, 15(4), 197–206. (2000)", + "url": "https://doi.org/10.1097/00004850-200015040-00002" + }, + { + "author": "Husain, Z., Hussain, K., Nair, R., & Steinman, R.", + "title": "Diphenhydramine induced QT prolongation and torsade de pointes: An uncommon effect of a common drug. Cardiology Journal, 17(5), 509–511. (2010)", + "url": "https://journals.viamedica.pl/cardiology_journal/article/view/21341" + }, + { + "author": "Khan, S., Saud, S., Khan, I., Asif, M., Ismail, O., Salam, A., Yang, T. J., & Norville, K. J.", + "title": "Serotonin Syndrome Presenting with Concomitant Tramadol and Diphenhydramine Use: A Case Report of an Unlikely Side-Effect. Cureus. (2018)", + "url": "https://doi.org/10.7759/cureus.2421" + }, + { + "author": "Massot, O., Rousselle, J.-C., Fillion, M.-P., Januel, D., Plantefol, M., & Fillion, G.", + "title": "5-HT1B Receptors: A Novel Target for Lithium: Possible Involvement in Mood Disorders. Neuropsychopharmacology, 21(4), 530–541. (1999)", + "url": "https://doi.org/10.1016/S0893-133X(99)00042-1" + }, + { + "author": "Mehta, N., & Vannozzi, R.", + "title": "Lithium‐induced electrocardiographic changes: A complete review. Clinical Cardiology, 40(12), 1363–1367. (2017)", + "url": "https://doi.org/10.1002/clc.22822" + }, + { + "author": "Müller-Oerlinghausen, B.", + "title": "Drug Interactions with Lithium: A Guide for Clinicians. CNS Drugs, 11(1), 41–48. (1999)", + "url": "https://doi.org/10.2165/00023210-199911010-00004" + }, + { + "author": "Rosenberg, A. E., Wang, R., & Rosenberg, M. H.", + "title": "Serotonin Syndrome Associated With High-dose Diphenhydramine Use Complicating Abdominoplasty and Mastopexy. Plastic and Reconstructive Surgery - Global Open, 13(3), e6634. (2025)", + "url": "https://doi.org/10.1097/GOX.0000000000006634" + }, + { + "author": "Truedson, P., Ott, M., Lindmark, K., Ström, M., Maripuu, M., Lundqvist, R., & Werneke, U.", + "title": "Effects of Toxic Lithium Levels on ECG—Findings from the LiSIE Retrospective Cohort Study. Journal of Clinical Medicine, 11(19), 5941. (2022)", + "url": "https://doi.org/10.3390/jcm11195941" + } + ], + "status": "Caution" + }, + "lsd": { + "note": "At 25-50mg, DPH may assist with side effects of the LSD such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and LSD is cautioned against. LSD is likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma. LSD and DPH at recreational dosages have additional cardiac concerns such as vasoconstriction, tachycardia, hypertension, which in combination may be exacerbated.", + "sources": [ + { + "author": "Marraffa, J. M. (2014)", + "title": "Drugs of Abuse. In Encyclopedia of Toxicology (pp. 248–251). Elsevier.", + "url": "https://doi.org/10.1016/B978-0-12-386454-3.00684-9" + }, + { + "author": "Passie, T., Halpern, J. H., Stichtenoth, D. O., Emrich, H. M., & Hintzen, A. (2008)", + "title": "The Pharmacology of Lysergic Acid Diethylamide: A Review. CNS Neuroscience & Therapeutics, 14(4), 295–314.", + "url": "https://doi.org/10.1111/j.1755-5949.2008.00059.x" + }, + { + "author": "Schaefer, T. S., Patel, P., & Zito, P. M. (2025)", + "title": "Antiemetic Histamine H1 Receptor Blockers. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK533003/" + }, + { + "author": "Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)", + "title": "Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.", + "url": "https://doi.org/10.3389/fpsyt.2021.657397" + }, + { + "author": "The drugs of misuse. (2009)", + "title": "In Auricular Acupuncture & Addiction (pp. 93–135). Elsevier.", + "url": "https://doi.org/10.1016/B978-0-443-06885-0.50018-5" + }, + { + "author": "Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)", + "title": "Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.", + "url": "https://doi.org/10.1016/j.jaip.2022.07.018" + } + ], + "status": "Caution" + }, + "maois": { + "note": "There is a significant risk of serotonin syndrome with this combination. Monoamine oxidase A inhibitors may extend and increase the anticholinergic effects of DPH. The combination increases each other’s side effects, such as drowsiness, dizziness, dry mouth, and headaches. Medical dosages are not reported to be of concern.", + "sources": [ + { + "author": "Adawi Awdish, R. L., Whitmill, M., Coba, V., & Killu, K. (2008)", + "title": "Serotonin Reuptake Inhibition by Diphenhydramine and concomitant Linezolid use can result in Serotonin Syndrome Chest, 134(4), 4C.", + "url": "https://doi.org/10.1378/chest.134.4_MeetingAbstracts.c4002" + }, + { + "author": "Clark, J. H., Meltzer, E. O., & Naclerio, R. M. (2025)", + "title": "Diphenhydramine: It is time to say a final goodbye. The World Allergy Organization Journal, 18(2), 101027.", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Edinoff, A. N., Swinford, C. R., Odisho, A. S., Burroughs, C. R., Stark, C. W., Raslan, W. A., Cornett, E. M., Kaye, A. M., & Kaye, A. D. (n.d.)", + "title": "Clinically Relevant Drug Interactions with Monoamine Oxidase Inhibitors. Health Psychology Research, 10(4), 39576.", + "url": "https://doi.org/10.52965/001c.39576" + }, + { + "author": "Gillman, P. K. (2005)", + "title": "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95(4), 434–441.", + "url": "https://doi.org/10.1093/bja/aei210" + }, + { + "author": "Khan, S., Saud, S., Khan, I., Asif, M., Ismail, O., Salam, A., Yang, T. J., & Norville, K. J. (2018)", + "title": "Serotonin Syndrome Presenting with Concomitant Tramadol and Diphenhydramine Use: A Case Report of an Unlikely Side-Effect. Cureus.", + "url": "https://doi.org/10.7759/cureus.2421" + }, + { + "author": "López-Álvarez, J., Sevilla-Llewellyn-Jones, J., & Agüera-Ortiz, L. (2019)", + "title": "Anticholinergic Drugs in Geriatric Psychopharmacology. Frontiers in Neuroscience, 13, 1309.", + "url": "https://doi.org/10.3389/fnins.2019.01309" + }, + { + "author": "Sub Laban, T., & Saadabadi, A. (2025)", + "title": "Monoamine Oxidase Inhibitors (MAOI). In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK539848/" + } + ], + "status": "Unsafe" + }, + "mephedrone": { + "note": "There is a high risk of serotonin syndrome at recreational dosages. Both can dull each other's effects, so if one wears off before the other it's possible to overdose due to the lack of counteraction. Medical dosages are reported not to be a concern for the general population. Both substances affect the heart and may lead to further dangerous heart complications at higher dosages. The combination may increase each other's side effects, such as dizziness and drowsiness. At higher dosages, the combination may increase each other's side effects, such as delirium, mania, and psychosis.", + "sources": [ + { + "author": "Clark, J. H., Meltzer, E. O., & Naclerio, R. M.", + "title": "Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027 (2025)", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Ener, R. A., Meglathery, S. B., Decker, W. A. V., & Gallagher, R. M.", + "title": "Serotonin Syndrome and Other Serotonergic Disorders: Table 1. Pain Medicine, 4(1), 63-74 (2003)", + "url": "https://doi.org/10.1046/j.1526-4637.2003.03005.x" + }, + { + "author": "Hadlock, G. C., Webb, K. M., McFadden, L. M., Chu, P. W., Ellis, J. D., Allen, S. C., Andrenyak, D. M., Vieira-Brock, P. L., German, C. L., Conrad, K. M., Hoonakker, A. J., Gibb, J. W., Wilkins, D. G., Hanson, G. R., & Fleckenstein, A. E.", + "title": "4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse. The Journal of Pharmacology and Experimental Therapeutics, 339(2), 530-536 (2011)", + "url": "https://doi.org/10.1124/jpet.111.184119" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T.", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats: Mephedrone increases both DA and 5-HT in rat brain. British Journal of Pharmacology, 164(8), 1949-1958 (2011)", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Meng, H., Cao, J., Kang, J., Ying, X., Ji, J., Reynolds, W., & Rampe, D.", + "title": "Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat. Toxicology Letters, 208(1), 62-68 (2012)", + "url": "https://doi.org/10.1016/j.toxlet.2011.10.010" + }, + { + "author": "Varghese, E., Abate, M. A., Hu, L., Kaplan, J., Kraner, J., Long, D. L., Sorg, M., Mock, A., Greenwald, M., & Andrew, T.", + "title": "Characterization of Diphenhydramine-Related Accidental Overdose Deaths. Academic Forensic Pathology, 5(1), 105-115 (2015)", + "url": "https://doi.org/10.23907/2015.011" + } + ], + "status": "Dangerous" + }, + "mescaline": { + "note": "At 25-50mg, DPH may assist with side effects of the mescaline such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and mescaline is cautioned against. Mescaline is likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma.", + "sources": [ + { + "author": "Dinis-Oliveira, R. J., Pereira, C. L., & Dias da Silva, D. (2019)", + "title": "Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions. Current Molecular Pharmacology, 12(3), 184–194.", + "url": "https://doi.org/10.2174/1874467211666181010154139" + }, + { + "author": "ScienceDirect Topics. (n.d.)", + "title": "Mescaline - an overview.", + "url": "https://www.sciencedirect.com/topics/neuroscience/mescaline" + }, + { + "author": "Schaefer, T. S., Patel, P., & Zito, P. M. (2025)", + "title": "Antiemetic Histamine H1 Receptor Blockers. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK533003/" + }, + { + "author": "Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)", + "title": "Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.", + "url": "https://doi.org/10.3389/fpsyt.2021.657397" + }, + { + "author": "Vamvakopoulou, I. A., Narine, K. A. D., Campbell, I., Dyck, J. R. B., & Nutt, D. J. (2023)", + "title": "Mescaline: The forgotten psychedelic. Neuropharmacology, 222, 109294.", + "url": "https://doi.org/10.1016/j.neuropharm.2022.109294" + }, + { + "author": "Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)", + "title": "Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.", + "url": "https://doi.org/10.1016/j.jaip.2022.07.018" + } + ], + "status": "Caution" + }, + "mushrooms": { + "note": "At 25-50mg, DPH may assist with side effects of the psilocybin such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and psilocybin is cautioned against. Psilocybin is likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma.", + "sources": [ + { + "author": "Goel, D. B., & Zilate, S. (2022)", + "title": "Potential Therapeutic Effects of Psilocybin: A Systematic Review. Cureus, 14(10), e30214.", + "url": "https://doi.org/10.7759/cureus.30214" + }, + { + "author": "Passie, T., Seifert, J., Schneider, U., & Emrich, H. M. (2002)", + "title": "The pharmacology of psilocybin. Addiction Biology, 7(4), 357–364.", + "url": "https://doi.org/10.1080/1355621021000005937" + }, + { + "author": "Schaefer, T. S., Patel, P., & Zito, P. M. (2025)", + "title": "Antiemetic Histamine H1 Receptor Blockers. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK533003/" + }, + { + "author": "Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)", + "title": "Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12.", + "url": "https://doi.org/10.3389/fpsyt.2021.657397" + }, + { + "author": "Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)", + "title": "Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.", + "url": "https://doi.org/10.1016/j.jaip.2022.07.018" + }, + { + "author": "Yerubandi, A., Thomas, J. E., Bhuiya, N. M. M. A., Harrington, C., Villa Zapata, L., & Caballero, J. (2024)", + "title": "Acute Adverse Effects of Therapeutic Doses of Psilocybin. JAMA Network Open, 7(4), e245960.", + "url": "https://doi.org/10.1001/jamanetworkopen.2024.5960" + } + ], + "status": "Caution" + }, + "mxe": { + "note": "There is a high risk of serotonin syndrome from this combination. Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. MXE has a high likelihood of increasing DPH's deliriant effects at higher dosages and can greatly increase the risk of injury, mania, and psychosis. Medical dosages are unlikely to be of concern.", + "sources": [ + { + "author": "Clark, J. H., Meltzer, E. O., & Naclerio, R. M. (2025)", + "title": "Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027.", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Ener, R. A., Meglathery, S. B., Decker, W. A. V., & Gallagher, R. M. (2003)", + "title": "Serotonin Syndrome and Other Serotonergic Disorders: Table 1. Pain Medicine, 4(1), 63–74.", + "url": "https://doi.org/10.1046/j.1526-4637.2003.03005.x" + }, + { + "author": "Marti, M., Talani, G., Miliano, C., Bilel, S., Biggio, F., Bratzu, J., Diana, M., De Luca, M. A., & Fattore, L. (2021)", + "title": "New insights into methoxetamine mechanisms of action: Focus on serotonergic 5-HT2 receptors in pharmacological and behavioral effects in the rat. Experimental Neurology, 345, 113836.", + "url": "https://doi.org/10.1016/j.expneurol.2021.113836" + }, + { + "author": "Roth, B. L., Gibbons, S., Arunotayanun, W., Huang, X.-P., Setola, V., Treble, R., & Iversen, L. (2013)", + "title": "The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor. PLoS ONE, 8(3), e59334.", + "url": "https://doi.org/10.1371/journal.pone.0059334" + }, + { + "author": "Varghese, E., Abate, M. A., Hu, L., Kaplan, J., Kraner, J., Long, D. L., Sorg, M., Mock, A., Greenwald, M., & Andrew, T. (2015)", + "title": "Characterization of Diphenhydramine-Related Accidental Overdose Deaths. Academic Forensic Pathology, 5(1), 105–115.", + "url": "https://doi.org/10.23907/2015.011" + } + ], + "status": "Dangerous" + }, + "nbomes": { + "note": "At 25-50mg, DPH may assist with side effects of the NBOMe drugs such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and NBOMe drugs is cautioned against. NBOMes are likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma. NBOMes and DPH at recreational dosages have additional cardiac concerns such as vasoconstriction, tachycardia, hypertension, which in combination may be exacerbated.", + "sources": [ + { + "author": "Kyriakou, C., Marinelli, E., Frati, P., Santurro, A., Afxentiou, M., Zaami, S., & Busardo, F. P. (2015)", + "title": "NBOMe: new potent hallucinogens--pharmacology, analytical methods, toxicities, fatalities: a review. European Review for Medical and Pharmacological Sciences, 19(17), 3270–3281.", + "url": "https://pubmed.ncbi.nlm.nih.gov/26400534/" + }, + { + "author": "Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)", + "title": "Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.", + "url": "https://doi.org/10.3389/fpsyt.2021.657397" + }, + { + "author": "Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)", + "title": "Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.", + "url": "https://doi.org/10.1016/j.jaip.2022.07.018" + }, + { + "author": "Zawilska, J. B., Kacela, M., & Adamowicz, P. (2020)", + "title": "NBOMes–Highly Potent and Toxic Alternatives of LSD. Frontiers in Neuroscience, 14, 78.", + "url": "https://doi.org/10.3389/fnins.2020.00078" + } + ], + "status": "Caution" + }, + "opioids": { + "note": "Both substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and unconsciousness. The interaction will cause greater inhibition and risk of injury. DPH reduces histamine release by opioids, which reduces the itching side effect from opioids. DPH may reduce the nausea caused by opioids. DPH inhibits CYP2D6 activity which can lead to a reduction of effects in some opioids and potentiation of effects in others.", + "sources": [ + { + "author": "Akutsu, T., Kobayashi, K., Sakurada, K., Ikegaya, H., Furihata, T., & Chiba, K. (2007)", + "title": "Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 35(1), 72–78.", + "url": "https://doi.org/10.1124/dmd.106.012088" + }, + { + "author": "Dinwiddie, A. T., Tanz, L. J., & Bitting, J. (2022)", + "title": "Notes from the Field: Antihistamine Positivity and Involvement in Drug Overdose Deaths — 44 Jurisdictions, United States, 2019–2020. Morbidity and Mortality Weekly Report, 71(41), 1308–1310.", + "url": "https://doi.org/10.15585/mmwr.mm7141a4" + }, + { + "author": "Grönlund, J., Saari, T. I., Hagelberg, N. M., Neuvonen, P. J., Olkkola, K. T., & Laine, K. (2010)", + "title": "Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 alone. British Journal of Clinical Pharmacology, 70(1), 78–87.", + "url": "https://doi.org/10.1111/j.1365-2125.2010.03653.x" + }, + { + "author": "Hamelin, B. (2000)", + "title": "Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity. Clinical Pharmacology & Therapeutics, 67(5), 466–477.", + "url": "https://doi.org/10.1067/mcp.2000.106464" + }, + { + "author": "Heiskanen, T., & Kalso, E. (2012)", + "title": "Non-analgesic effects of opioids: interactions between opioids and other drugs. Current Pharmaceutical Design, 18(37), 6079–6089.", + "url": "https://doi.org/10.2174/138161212803582423" + }, + { + "author": "Nahid, N. A., McDonough, C. W., Wei, Y.-J. J., Cicali, E. J., Gong, Y., Fillingim, R. B., & Johnson, J. A. (2024)", + "title": "Use of CYP2D6 Inhibitors with CYP2D6 Opioids: Association with Emergency Department Visits for Pain. Clinical Pharmacology and Therapeutics, 116(4), 1005–1012.", + "url": "https://doi.org/10.1002/cpt.3314" + }, + { + "author": "Okutani, H., Lo Vecchio, S., & Arendt‐Nielsen, L. (2024)", + "title": "Mechanisms and treatment of opioid‐induced pruritus: Peripheral and central pathways. European Journal of Pain, 28(2), 214–230.", + "url": "https://doi.org/10.1002/ejp.2180" + }, + { + "author": "Sicari, V., Patel, P., & Zabbo, C. P. (2025)", + "title": "Diphenhydramine. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + }, + { + "author": "Swegle, J. M., & Logemann, C. (2006)", + "title": "Management of common opioid-induced adverse effects. American Family Physician, 74(8), 1347–1354.", + "url": "https://pubmed.ncbi.nlm.nih.gov/17087429/" + }, + { + "author": "Wei, Y.-J. J., Winterstein, A. G., Schmidt, S., Fillingim, R. B., Daniels, M. J., DeKosky, S. T., & Schmidt, S. (2025)", + "title": "Association of initiating CYP2D6-metabolized opioids with risks of adverse outcomes in older adults receiving antidepressants: A retrospective cohort study. PLOS Medicine, 22(6), e1004620.", + "url": "https://doi.org/10.1371/journal.pmed.1004620" + }, + { + "author": "Whitt, A., & Jortani, S. (2023)", + "title": "B-337 Case Report: Fatal Opioid Overdose Induced by Over-the-Counter Cold Medication Diphenhydramine. Clinical Chemistry, 69(Supplement_1), hvad097.656.", + "url": "https://doi.org/10.1093/clinchem/hvad097.656" + } + ], + "status": "Unsafe" + }, + "pregabalin": { + "note": "There is a significant risk of seizures from this combination. The combination is likely to increase each other’s negative side effects, such as nausea, dizziness, and loss of consciousness. At higher dosages, pregabalin is likely to increase diphenhydramine’s deliriant effects, inhibition, and risk of injury. Medical dosages are not reported to be a concern.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Medline Plus Medical Encyclopedia (2023)", + "title": "Diphenhydramine overdose", + "url": "https://medlineplus.gov/ency/article/002636.htm" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "Fakhr, M. S., Motamed Chaboki, P., Ashayeri, H., Sahranavard, P., Mohammadipanah, S., & Zamanabadi, M. N. (2023)", + "title": "Comparison of the effects of pregabalin and famotidine with pregabalin and diphenhydramine on postoperative abdominal pain. International Journal of Surgery Open, 58, 100674.", + "url": "https://doi.org/10.1016/j.ijso.2023.100674" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Jang, D. H., Manini, A. F., Trueger, N. S., Duque, D., Nestor, N. B., Nelson, L. S., & Hoffman, R. S. (2010)", + "title": "Status epilepticus and wide-complex tachycardia secondary to diphenhydramine overdose. Clinical Toxicology, 48(9), 945–948.", + "url": "https://doi.org/10.3109/15563650.2010.527850" + }, + { + "author": "Kim, H., Kim, S. H., & Kim, J. B. (2021)", + "title": "Antihistamines as a common cause of new-onset seizures: a single-center observational study. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 42(6), 2505–2508.", + "url": "https://doi.org/10.1007/s10072-021-05043-2" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)", + "title": "Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.", + "url": "https://doi.org/10.3389/fpsyt.2021.657397" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)", + "title": "Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.", + "url": "https://doi.org/10.1016/j.jaip.2022.07.018" + } + ], + "status": "Unsafe" + }, + "ssris": { + "note": "There is a high risk of serotonin syndrome at recreational dosages. Medical dosages are reported not to be a concern for the general population. The combination may increase each other's side effects, such as dizziness and drowsiness.", + "sources": [ + { + "author": "Clark, J. H., Meltzer, E. O., & Naclerio, R. M.", + "title": "Diphenhydramine: It is time to say a final goodbye. The World Allergy Organization Journal, 18(2), 101027 (2025)", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Ener, R. A., Meglathery, S. B., Decker, W. A. V., & Gallagher, R. M.", + "title": "Serotonin Syndrome and Other Serotonergic Disorders: Table 1. Pain Medicine, 4(1), 63-74 (2003)", + "url": "https://doi.org/10.1046/j.1526-4637.2003.03005.x" + }, + { + "author": "Khan, S., Saud, S., Khan, I., Asif, M., Ismail, O., Salam, A., Yang, T. J., & Norville, K. J.", + "title": "Serotonin Syndrome Presenting with Concomitant Tramadol and Diphenhydramine Use: A Case Report of an Unlikely Side-Effect. Cureus, 10(4), e2421 (2018)", + "url": "https://doi.org/10.7759/cureus.2421" + }, + { + "author": "Lane, R., Baldwin, D., & Preskorn, S.", + "title": "The SSRIs: advantages, disadvantages and differences. Journal of Psychopharmacology, 9(2 Suppl), 163-178 (1995)", + "url": "https://doi.org/10.1177/0269881195009002011" + }, + { + "author": "Sproule, B. A., Naranjo, C. A., Brenmer, K. E., & Hassan, P. C.", + "title": "Selective serotonin reuptake inhibitors and CNS drug interactions. A critical review of the evidence. Clinical Pharmacokinetics, 33(6), 454-471 (1997)", + "url": "https://doi.org/10.2165/00003088-199733060-00004" + }, + { + "author": "van Harten, J.", + "title": "Clinical pharmacokinetics of selective serotonin reuptake inhibitors. Clinical Pharmacokinetics, 24(3), 203-220 (1993)", + "url": "https://doi.org/10.2165/00003088-199324030-00003" + }, + { + "author": "Varghese, E., Abate, M. A., Hu, L., Kaplan, J., Kraner, J., Long, D. L., Sorg, M., Mock, A., Greenwald, M., & Andrew, T.", + "title": "Characterization of Diphenhydramine-Related Accidental Overdose Deaths. Academic Forensic Pathology, 5(1), 105-115 (2015)", + "url": "https://doi.org/10.23907/2015.011" + } + ], + "status": "Dangerous" + }, + "tramadol": { + "note": "Both drugs increase the risk of serotonin syndrome. While at medical dosages, this is unlikely to be of concern, recreational doses should be avoided. Diphenhydramine may increase tramadol’s seizure risk.", + "sources": [ + { + "author": "Benson, B. E., Farooqi, M. F., Klein-Schwartz, W., Litovitz, T., Webb, A. N., Borys, D. J., Lung, D., Rutherfoord Rose, S., Aleguas, A., Sollee, D. R., & Seifert, S. A. (2010)", + "title": "Diphenhydramine dose–response: a novel approach to determine triage thresholds. Clinical Toxicology, 48(8), 820–831.", + "url": "https://doi.org/10.3109/15563650.2010.514269" + }, + { + "author": "Dhesi, M., Maldonado, K. A., Patel, P., & Maani, C. V. (2025)", + "title": "Tramadol. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK537060/" + }, + { + "author": "Hughes, A. R., Lin, A., Hendrickson, R. G., & on behalf of Toxicology Investigator’s Consortium (ToxIC). (2021)", + "title": "Clinical and patient characteristics associated with severe outcome in diphenhydramine toxicity. Clinical Toxicology, 59(10), 918–925.", + "url": "https://doi.org/10.1080/15563650.2021.1891244" + }, + { + "author": "Khan, S., Saud, S., Khan, I., Asif, M., Ismail, O., Salam, A., Yang, T. J., & Norville, K. J. (2018)", + "title": "Serotonin Syndrome Presenting with Concomitant Tramadol and Diphenhydramine Use: A Case Report of an Unlikely Side-Effect. Cureus.", + "url": "https://doi.org/10.7759/cureus.2421" + }, + { + "author": "Kim, H., Kim, S. H., & Kim, J. B. (2021)", + "title": "Antihistamines as a common cause of new-onset seizures: a single-center observational study. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 42(6), 2505–2508.", + "url": "https://doi.org/10.1007/s10072-021-05043-2" + }, + { + "author": "Kim, H., Wang, I.-N., Park, J.-S., Kim, K.-T., Kong, J., Kim, J. B., & Kim, D.-J. (2023)", + "title": "Inherent seizure susceptibility in patients with antihistamine-induced acute symptomatic seizure: a resting-state EEG analysis. Scientific Reports, 13(1), 9146.", + "url": "https://doi.org/10.1038/s41598-023-36415-7" + }, + { + "author": "Sanaei-Zadeh, H. (2012)", + "title": "Diphenhydramine overdose and serotonin syndrome. Psychiatry and Clinical Neurosciences, 66(3), 244–245.", + "url": "https://doi.org/10.1111/j.1440-1819.2012.02320.x" + }, + { + "author": "Sicari, V., Patel, P., & Zabbo, C. P. (2025)", + "title": "Diphenhydramine. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + } + ], + "status": "Dangerous" + } + }, + "dmt": { + "2c-t-x": { + "status": "Low Risk & Synergy" + }, + "2c-x": { + "status": "Low Risk & Synergy" + }, + "5-meo-xxt": { + "status": "Low Risk & Synergy" + }, + "alcohol": { + "status": "Low Risk & Decrease" + }, + "amphetamines": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "amt": { + "status": "Low Risk & Synergy" + }, + "benzodiazepines": { + "status": "Low Risk & Decrease" + }, + "caffeine": { + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "cocaine": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "dextromethorphan": { + "status": "Low Risk & Synergy" + }, + "diphenhydramine": { + "note": "At 25-50mg, DPH may assist with side effects of the DMT such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and DMT is cautioned against. DMT is likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma.", + "sources": [ + { + "author": "Carbonaro, T. M., & Gatch, M. B. (2016)", + "title": "Neuropharmacology of N,N-Dimethyltryptamine. Brain Research Bulletin, 126(Pt 1), 74–88.", + "url": "https://doi.org/10.1016/j.brainresbull.2016.04.016" + }, + { + "author": "Chapy, H., Smirnova, M., André, P., Schlatter, J., Chiadmi, F., Couraud, P.-O., Scherrmann, J.-M., Declèves, X., & Cisternino, S. (2014)", + "title": "Carrier-Mediated Cocaine Transport at the Blood-Brain Barrier as a Putative Mechanism in Addiction Liability. International Journal of Neuropsychopharmacology, 18(1), pyu001.", + "url": "https://doi.org/10.1093/ijnp/pyu001" + }, + { + "author": "Schaefer, T. S., Patel, P., & Zito, P. M. (2025)", + "title": "Antiemetic Histamine H1 Receptor Blockers. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK533003/" + }, + { + "author": "Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)", + "title": "Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.", + "url": "https://doi.org/10.3389/fpsyt.2021.657397" + }, + { + "author": "Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)", + "title": "Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.", + "url": "https://doi.org/10.1016/j.jaip.2022.07.018" + } + ], + "status": "Caution" + }, + "dox": { + "status": "Low Risk & Synergy" + }, + "ghb/gbl": { + "status": "Low Risk & Decrease" + }, + "ketamine": { + "status": "Low Risk & Synergy" + }, + "lithium": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + } + ], + "status": "Dangerous" + }, + "lsd": { + "status": "Low Risk & Synergy" + }, + "maois": { + "status": "Low Risk & Synergy" + }, + "mdma": { + "status": "Low Risk & Synergy" + }, + "mephedrone": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "sources": [ + { + "author": "Carbonaro, T. M., & Gatch, M. B.", + "title": "Neuropharmacology of N,N-Dimethyltryptamine. Brain Research Bulletin, 126(Pt 1), 74–88 (2016)", + "url": "https://doi.org/10.1016/j.brainresbull.2016.04.016" + }, + { + "author": "Erhorn, S.", + "title": "Dimethyltryptamine. In xPharm: The Comprehensive Pharmacology Reference, 1–4 (2007)", + "url": "https://doi.org/10.1016/B978-008055232-3.62227-5" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T.", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats. British Journal of Pharmacology, 164(8), 1949–1958 (2011)", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Papaseit, E., Moltó, J., Muga, R., Torrens, M., de la Torre, R., & Farré, M.", + "title": "Clinical Pharmacology of the Synthetic Cathinone Mephedrone. In M. H. Baumann, R. A. Glennon, & J. L. Wiley (Eds.), Neuropharmacology of New Psychoactive Substances (NPS): The Science Behind the Headlines, 313–331 (2017)", + "url": "https://doi.org/10.1007/7854_2016_61" + }, + { + "author": "Wood, D. M., Davies, S., Greene, S. L., Button, J., Holt, D. W., Ramsey, J., & Dargan, P. I.", + "title": "Case series of individuals with analytically confirmed acute mephedrone toxicity. Clinical Toxicology, 48(9), 924–927 (2010)", + "url": "https://doi.org/10.3109/15563650.2010.531021" + } + ], + "status": "Low Risk & Synergy" + }, + "mescaline": { + "status": "Low Risk & Synergy" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "status": "Low Risk & Synergy" + }, + "nbomes": { + "status": "Low Risk & Synergy" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "status": "Low Risk & No Synergy" + }, + "pcp": { + "status": "Low Risk & Synergy" + }, + "pregabalin": { + "note": "Pregabalin may reduce the anxiety and other possible side effects of DMT. Additionally, the combination may increase inhibition, dizziness, and risk of injury.", + "sources": [ + { + "author": "Carbonaro, T. M., & Gatch, M. B. (2016)", + "title": "Neuropharmacology of N,N-Dimethyltryptamine. Brain Research Bulletin, 126(Pt 1), 74–88.", + "url": "https://doi.org/10.1016/j.brainresbull.2016.04.016" + }, + { + "author": "Cross, A. L., Viswanath, O., & Sherman, A. L. (2025)", + "title": "Pregabalin. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK470341/" + } + ], + "status": "Low Risk & Synergy" + }, + "ssris": { + "status": "Low Risk & Decrease" + }, + "tramadol": { + "note": "Tramadol is well known to lower seizure threshold and psychedelics also cause occasional seizures.", + "status": "Unsafe" + } + }, + "dox": { + "2c-t-x": { + "status": "Caution" + }, + "2c-x": { + "status": "Caution" + }, + "5-meo-xxt": { + "note": "The 5-MeO class of tryptamines can be unpredictable in their interactions, particularly increasing the risk of unpleasant physical side effects.", + "status": "Caution" + }, + "alcohol": { + "note": "Drinking on stimulants is risky because the sedative effects of the alcohol are reduced, and these are what the body uses to gauge drunkenness. This typically leads to excessive drinking with greatly reduced inhibitions, high risk of liver damage and increased dehydration. They will also allow you to drink past a point where you might normally pass out, increasing the risk.", + "status": "Low Risk & Decrease" + }, + "amphetamines": { + "note": "The combined stimulating effects of the two can lead to an uncomfortable body-load, while the focusing effects of amphetamine can easily lead to thought loops. Coming down from amphetamines while the DOx is still active can be quite anxiogenic. ", + "status": "Unsafe" + }, + "amt": { + "status": "Dangerous" + }, + "benzodiazepines": { + "status": "Low Risk & Decrease" + }, + "caffeine": { + "note": "High doses of caffeine may cause anxiety which is less manageable when tripping, and since both are stimulating it may cause some physical discomfort.", + "status": "Caution" + }, + "cannabis": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "cocaine": { + "note": "The combined stimulating effects of the two can lead to an uncomfortable body-load, while the focusing effects of cocaine can easily lead to thought loops. Coming down from cocaine while the DOx is still active can be quite anxiogenic", + "status": "Unsafe" + }, + "dextromethorphan": { + "note": "The DOx class as psychedelic stimulants have the potential to mask the effects of DXM and could lead to redosing to an unsafe level. DXM can also potentiate DOx resulting in an unpleasantly intense experience.", + "status": "Unsafe" + }, + "diphenhydramine": { + "note": "At 25-50mg, DPH may assist with side effects of DOx drugs such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and DOx drugs is cautioned against. DOx drugs are likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma. DOx drugs and DPH at recreational dosages have additional cardiac concerns such as vasoconstriction, tachycardia, hypertension, which in combination may be exacerbated.", + "sources": [ + { + "author": "ScienceDirect Topics (n.d.)", + "title": "2,5-Dimethoxy-4-iodoamphetamine - an overview", + "url": "https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/2-5-dimethoxy-4-iodoamphetamine" + }, + { + "author": "Barnett, R. Y., Baker, D. D., Kelly, N. E., McGuire, C. E., Fassette, T. C., & Gorniak, J. M. (2014)", + "title": "A Fatal Intoxication of 2,5-Dimethoxy-4-Chloroamphetamine: A Case Report. Journal of Analytical Toxicology, 38(8), 589–591.", + "url": "https://doi.org/10.1093/jat/bku087" + }, + { + "author": "Burish, M. J., Thoren, K. L., Madou, M., Toossi, S., & Shah, M. (2015)", + "title": "Hallucinogens Causing Seizures? A Case Report of the Synthetic Amphetamine 2,5-Dimethoxy-4-Chloroamphetamine. The Neurohospitalist, 5(1), 32–34.", + "url": "https://doi.org/10.1177/1941874414528939" + }, + { + "author": "Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)", + "title": "Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.", + "url": "https://doi.org/10.3389/fpsyt.2021.657397" + }, + { + "author": "Trout, K., & Daley, P. F. (2024)", + "title": "The origin of 2,5‐dimethoxy‐4‐methylamphetamine (DOM, STP). Drug Testing and Analysis, 16(12), 1496–1508.", + "url": "https://doi.org/10.1002/dta.3667" + }, + { + "author": "Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)", + "title": "Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.", + "url": "https://doi.org/10.1016/j.jaip.2022.07.018" + } + ], + "status": "Caution" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "ghb/gbl": { + "status": "Low Risk & Decrease" + }, + "ketamine": { + "note": "Ketamine and psychedelics tend to potentiate each other - go slowly.", + "status": "Low Risk & Synergy" + }, + "lithium": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + } + ], + "status": "Dangerous" + }, + "lsd": { + "status": "Low Risk & Synergy" + }, + "maois": { + "note": "MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably", + "status": "Caution" + }, + "mdma": { + "note": "The combined stimulating effects of the two can be uncomfortable. Coming down on the MDMA while the DOx is still active can be quite anxiogenic. ", + "status": "Caution" + }, + "mephedrone": { + "note": "The anxiogenic and focusing effects of stimulants increase the chance of unpleasant thought loops, in addition to the possible negative side effects of coming down from said stimulant while on a psychedelic. In extreme cases, stimulants, especially in combination can result in severe vasoconstriction, tachycardia, hypertension, and heart failure.", + "sources": [ + { + "author": "ScienceDirect Topics (n.d.)", + "title": "2,5-Dimethoxy-4-iodoamphetamine - an overview", + "url": "https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/2-5-dimethoxy-4-iodoamphetamine" + }, + { + "author": "Dargan, P. I., Sedefov, R., Gallegos, A., & Wood, D. M. (2011)", + "title": "The pharmacology and toxicology of the synthetic cathinone mephedrone (4‐methylmethcathinone). Drug Testing and Analysis, 3(7–8), 454–463", + "url": "https://doi.org/10.1002/dta.312" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T. (2011)", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats: Mephedrone increases both DA and 5-HT in rat brain. British Journal of Pharmacology, 164(8), 1949–1958", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Trout, K., & Daley, P. F. (2024)", + "title": "The origin of 2,5‐dimethoxy‐4‐methylamphetamine (DOM, STP). Drug Testing and Analysis, 16(12), 1496–1508", + "url": "https://doi.org/10.1002/dta.3667" + } + ], + "status": "Caution" + }, + "mescaline": { + "status": "Caution" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "note": "As an NMDA antagonist MXE potentiates DOx which can be unpleasantly intense", + "status": "Caution" + }, + "nbomes": { + "status": "Caution" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "note": "No unexpected interactions.", + "status": "Low Risk & No Synergy" + }, + "pcp": { + "note": "Details of this combination are not well understood but PCP generally interacts in an unpredictable manner.", + "status": "Unsafe" + }, + "pregabalin": { + "note": "Caution should be given due to DOx drugs stimulating effects and pregabalin’s seizure concerns at higher dosages. Pregabalin may reduce the vasoconstriction, anxiety, and other side effects of DOx drugs. Additionally, Pregabalin may increase DOx drugs inhibition and risk of injury.", + "sources": [ + { + "author": "ScienceDirect Topics (n.d.)", + "title": "2,5-Dimethoxy-4-iodoamphetamine - an overview", + "url": "https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/2-5-dimethoxy-4-iodoamphetamine" + }, + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Barnett, R. Y., Baker, D. D., Kelly, N. E., McGuire, C. E., Fassette, T. C., & Gorniak, J. M. (2014)", + "title": "A Fatal Intoxication of 2,5-Dimethoxy-4-Chloroamphetamine: A Case Report. Journal of Analytical Toxicology, 38(8), 589–591.", + "url": "https://doi.org/10.1093/jat/bku087" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Burish, M. J., Thoren, K. L., Madou, M., Toossi, S., & Shah, M. (2015)", + "title": "Hallucinogens Causing Seizures? A Case Report of the Synthetic Amphetamine 2,5-Dimethoxy-4-Chloroamphetamine. The Neurohospitalist, 5(1), 32–34.", + "url": "https://doi.org/10.1177/1941874414528939" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Jacob, P., & Shulgin, A. T. (1994)", + "title": "Structure-activity relationships of the classic hallucinogens and their analogs. NIDA Research Monograph, 146, 74–91.", + "url": "https://pubmed.ncbi.nlm.nih.gov/8742795/" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Luethi, D., Rudin, D., Hoener, M. C., & Liechti, M. E. (2022)", + "title": "Monoamine Receptor and Transporter Interaction Profiles of 4‐Alkyl‐Substituted 2,5‐Dimethoxyamphetamines. The FASEB Journal, 36(S1), fasebj.2022.36.S1.R2691.", + "url": "https://doi.org/10.1096/fasebj.2022.36.S1.R2691" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Trout, K., & Daley, P. F. (2024)", + "title": "The origin of 2,5‐dimethoxy‐4‐methylamphetamine (DOM, STP). Drug Testing and Analysis, 16(12), 1496–1508.", + "url": "https://doi.org/10.1002/dta.3667" + } + ], + "status": "Caution" + }, + "ssris": { + "status": "Low Risk & Decrease" + }, + "tramadol": { + "note": "Tramadol is well known to lower seizure threshold and psychedelics also cause occasional seizures.", + "status": "Unsafe" + } + }, + "ghb/gbl": { + "2c-t-x": { + "status": "Low Risk & Decrease" + }, + "2c-x": { + "status": "Low Risk & Decrease" + }, + "5-meo-xxt": { + "status": "Low Risk & Decrease" + }, + "alcohol": { + "note": "Even in very low doses this combination rapidly leads to memory loss, severe ataxia and unconsciousness. There is a high risk of vomit aspiration while unconscious.", + "status": "Dangerous" + }, + "amphetamines": { + "note": "Stimulants increase respiration rate allowing for a higher dose of sedatives than normal. If the stimulant wears off first the opiate may overcome the individual and cause respiratory arrest.", + "status": "Caution" + }, + "amt": { + "status": "Low Risk & Decrease" + }, + "benzodiazepines": { + "note": "The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position.", + "status": "Dangerous" + }, + "caffeine": { + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "status": "Low Risk & Synergy" + }, + "cocaine": { + "note": "Stimulants increase respiration rate allowing for a higher dose of sedatives than normal. If the stimulant wears off first the opiate may overcome the individual and cause respiratory arrest. Likewise the ghb/gbl can wear off and leave a dangerous concentration of cocaine behind", + "status": "Caution" + }, + "dextromethorphan": { + "note": "Both substances cause ataxia and bring a risk of vomiting and unconsciousness. If the individual falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position. This combination is hard to predict", + "status": "Dangerous" + }, + "diphenhydramine": { + "note": "Both substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and unconsciousness. The interaction will cause greater inhibition and risk of injury. If the user falls unconscious it is strongly recommended to put them into the recovery position and monitor breathing.", + "sources": [ + { + "author": "William J Tharion, Donna J. McMenemy, Terry M. Rauch", + "title": "Antihistamine Effects on the Central Nervous System, Cognitive Performance and Subjective States. ", + "url": "https://doi.org/10.1159/000119069" + }, + { + "author": "Sicari V, Zabbo CP. Diphenhydramine.", + "title": "Diphenhydramine", + "url": "https://www.ncbi.nlm.nih.gov/books/NBK526010/" + }, + { + "author": "Couper FJ, Marinetti LJ.", + "title": "γ-Hydroxybutyrate (GHB) - Effects on Human Performance and Behavior ", + "url": "https://pubmed.ncbi.nlm.nih.gov/26256488/" + }, + { + "author": "Busardò FP, Jones AW.", + "title": "GHB Pharmacology and Toxicology: Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome", + "url": "https://doi.org/10.2174%2F1570159X13666141210215423" + } + ], + "status": "Dangerous" + }, + "dmt": { + "status": "Low Risk & Decrease" + }, + "dox": { + "status": "Low Risk & Decrease" + }, + "ketamine": { + "note": "Both substances cause ataxia and bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.", + "status": "Dangerous" + }, + "lsd": { + "status": "Low Risk & Decrease" + }, + "maois": { + "status": "Low Risk & Synergy" + }, + "mdma": { + "note": "Large amounts of GHB/GBL may overwhelm the effects of MDMA on the comedown.", + "status": "Caution" + }, + "mephedrone": { + "note": "Both can dull each other's effects, so if one wears off before the other it's possible to overdose due to the lack of counteraction. Both substances affect the heart and may lead to further dangerous heart complications at higher dosages. Additionally, the combination may increase the negative side effects of each other.", + "sources": [ + { + "author": "Aromatario, M., Bottoni, E., Santoni, M., & Ciallella, C.", + "title": "New \"Lethal highs\": A case of a deadly cocktail of GHB and Mephedrone. Forensic Science International, 223(1), e38–e41 (2012)", + "url": "https://doi.org/10.1016/j.forsciint.2012.09.014" + }, + { + "author": "Drugs.ie", + "title": "Drug Combinations \"Mixing Drugs\" - Drug and Alcohol Information and Support in Ireland (2025)", + "url": "https://www.drugs.ie/drugs_info/about_drugs/poly_drug_use1/" + }, + { + "author": "Felmlee, M. A., Morse, B. L., & Morris, M. E.", + "title": "γ-Hydroxybutyric Acid: Pharmacokinetics, Pharmacodynamics, and Toxicology. The AAPS Journal, 23(1), 22 (2021)", + "url": "https://doi.org/10.1208/s12248-020-00543-z" + }, + { + "author": "Galicia, M., Nogue, S., & Miró, O.", + "title": "Liquid ecstasy intoxication: clinical features of 505 consecutive emergency department patients. Emergency Medicine Journal: EMJ, 28(6), 462–466 (2011)", + "url": "https://doi.org/10.1136/emj.2008.068403" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T.", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats. British Journal of Pharmacology, 164(8), 1949–1958 (2011)", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Kozina, L., Grizelj Benussi, M., & Sutara, N.", + "title": "Novel Psychoactive Substances – GHB- and Mephedrone-Induced Delirium Treated with Olanzapine: A Case Report and Literature Review. Medicina Fluminensis, 61(3), 318–326 (2025)", + "url": "https://doi.org/10.21860/medflum2025_332196" + }, + { + "author": "Mayer, F. P., Niello, M., Bulling, S., Zhang, Y.-W., Li, Y., Kudlacek, O., Holy, M., Kooti, F., Sandtner, W., Rudnick, G., Schmid, D., & Sitte, H. H.", + "title": "Mephedrone induces partial release at human dopamine transporters but full release at human serotonin transporters. Neuropharmacology, 240, 109704 (2023)", + "url": "https://doi.org/10.1016/j.neuropharm.2023.109704" + }, + { + "author": "Papaseit, E., Moltó, J., Muga, R., Torrens, M., de la Torre, R., & Farré, M.", + "title": "Clinical Pharmacology of the Synthetic Cathinone Mephedrone. Neuropharmacology of New Psychoactive Substances (NPS): The Science Behind the Headlines, pp. 313–331 (2017)", + "url": "https://doi.org/10.1007/7854_2016_61" + }, + { + "author": "Wood, D. M., Davies, S., Greene, S. L., Button, J., Holt, D. W., Ramsey, J., & Dargan, P. I.", + "title": "Case series of individuals with analytically confirmed acute mephedrone toxicity. Clinical Toxicology, 48(9), 924–927 (2010)", + "url": "https://doi.org/10.3109/15563650.2010.531021" + } + ], + "status": "Caution" + }, + "mescaline": { + "status": "Low Risk & Decrease" + }, + "mushrooms": { + "status": "Low Risk & Decrease" + }, + "mxe": { + "note": "Both substances cause ataxia and bring a risk of vomiting and unconsciousness. If the individual falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.", + "status": "Dangerous" + }, + "nbomes": { + "status": "Low Risk & Decrease" + }, + "nitrous": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are likely.", + "status": "Caution" + }, + "opioids": { + "note": "The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position", + "status": "Dangerous" + }, + "pcp": { + "note": "Details of this combination are not well understood but PCP generally interacts in an unpredictable manner.", + "status": "Dangerous" + }, + "pregabalin": { + "note": "The two substances potentiate each other strongly and unpredictably, and may rapidly lead to unconsciousness. They both increase each other's side effects such as ataxia, sedation, and CNS depression. Blackout and memory loss risk is significantly increased. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position. There is an increased risk of seizures from this combination.", + "sources": [ + { + "author": "Cagnin, A., Pompanin, S., Manfioli, V., Briani, C., Zambon, A., Saladini, M., & Dam, M. (2011)", + "title": "γ-Hydroxybutyric acid-induced psychosis and seizures.", + "url": "https://doi.org/10.1016/j.yebeh.2011.03.009" + }, + { + "author": "Castelli, M. P., Ferraro, L., Mocci, I., Carta, F., Carai, M. A. M., Antonelli, T., Tanganelli, S., Cignarella, G., & Gessa, G. L. (2003)", + "title": "Selective γ‐hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ‐hydroxybutyric acid.", + "url": "https://doi.org/10.1046/j.1471-4159.2003.02037.x" + }, + { + "author": "Eipe, N., & Penning, J. (2011)", + "title": "Postoperative Respiratory Depression Associated with Pregabalin: A Case Series and a Preoperative Decision Algorithm.", + "url": "https://doi.org/10.1155/2011/561604" + }, + { + "author": "Elliott, S. P., Burke, T., & Smith, C. (2017)", + "title": "Determining the Toxicological Significance of Pregabalin in Fatalities.", + "url": "https://doi.org/10.1111/1556-4029.13263" + }, + { + "author": "Evoy, K. E., Sadrameli, S., Contreras, J., Covvey, J. R., Peckham, A. M., & Morrison, M. D. (2021)", + "title": "Abuse and Misuse of Pregabalin and Gabapentin: A Systematic Review Update.", + "url": "https://doi.org/10.1007/s40265-020-01432-7" + }, + { + "author": "Galloway, G. P., Frederick, S. L., Staggers, F. E., Gonzales, M., Stalcup, S. A., & Smith, D. E. (1997)", + "title": "Gamma-hydroxybutyrate: an emerging drug of abuse that causes physical dependence.", + "url": "https://pubmed.ncbi.nlm.nih.gov/9060200/" + }, + { + "author": "Le, J. K., & Richards, J. R. (2025a)", + "title": "Gamma-Hydroxybutyrate Toxicity. In StatPearls.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK430781/" + }, + { + "author": "Le, J. K., & Richards, J. R. (2025b)", + "title": "Gamma-Hydroxybutyrate Toxicity. In StatPearls.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK430781/" + }, + { + "author": "Oskouei, Z., Moshiri, M., Raouf-Rahmati, A., Nemati, A., Bemani Naeini, M., Jomehpour, H., Roohbakhsh, A., Salmasi, Z., & Etemad, L. (2025)", + "title": "Seizures as an Adverse Effect of Pregabalin Consumption: A Systematic Review.", + "url": "https://doi.org/10.34172/ahj.1527" + }, + { + "author": "Venzi, M., Di Giovanni, G., & Crunelli, V. (2014)", + "title": "A Critical Evaluation of the Gamma‐Hydroxybutyrate (GHB) Model of Absence Seizures.", + "url": "https://doi.org/10.1111/cns.12337" + }, + { + "author": "Winters, W. D., & Spooner, C. E. (1965)", + "title": "Various seizure activities following gamma-hydroxybutyrate.", + "url": "https://doi.org/10.1016/0028-3908(65)90034-1" + } + ], + "status": "Dangerous" + }, + "ssris": { + "status": "Low Risk & No Synergy" + }, + "tramadol": { + "note": "The sedative effects of this combination can lead to dangerous respiratory depression.", + "status": "Dangerous" + } + }, + "ketamine": { + "2c-t-x": { + "status": "Low Risk & Synergy" + }, + "2c-x": { + "status": "Low Risk & Synergy" + }, + "5-meo-xxt": { + "status": "Low Risk & Synergy" + }, + "alcohol": { + "note": "Both substances cause ataxia and bring a very high risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.", + "status": "Dangerous" + }, + "amphetamines": { + "note": "No unexpected interactions, though likely to increase blood pressure but not an issue with sensible doses. Moving around on high doses of this combination may be ill advised due to risk of physical injury.", + "status": "Caution" + }, + "amt": { + "status": "Low Risk & Synergy" + }, + "benzodiazepines": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position.", + "status": "Caution" + }, + "caffeine": { + "note": "No unexpected interactions.", + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "status": "Low Risk & Synergy" + }, + "cocaine": { + "note": "No unexpected interactions, though likely to increase blood pressure but not an issue with sensible doses. Moving around on high doses of this combination may be ill advised due to risk of physical injury.", + "status": "Caution" + }, + "dextromethorphan": { + "note": "Both substances primarily exert their effects through NMDA antagonism. Currently, there is no evidence regarding mechanisms that might reduce these effects.", + "sources": [ + { + "author": "Jeanna M. Marraffa", + "title": "Dextromethorphan", + "url": "https://doi.org/10.1016/B978-0-12-824315-2.00127-5" + }, + { + "author": "Georges Mion, Thierry Villevieille", + "title": "Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings)", + "url": "https://doi.org/10.1111/cns.12099" + }, + { + "author": "P. Klepstad, P. C. Borchgrevink", + "title": "Four years' treatment with ketamine and a trial of dextromethorphan in a patient with severe post-herpetic neuralgia", + "url": "https://doi.org/10.1111/j.1399-6576.1997.tb04709.x" + }, + { + "author": "Stephen M. Stahl", + "title": "Mechanism of action of dextromethorphan/quinidine: comparison with ketamine", + "url": "https://doi.org/10.1017/S109285291300062X" + }, + { + "author": "A M Hughes,1 J Rhodes,1 G Fisher,2 M Sellers,3 and J W Growcott1", + "title": "Assessment of the effect of dextromethorphan and ketamine on the acute nociceptive threshold and wind-up of the second pain response in healthy male volunteers", + "url": "https://doi.org/10.1046%2Fj.1365-2125.2002.01602.x" + }, + { + "author": "Keiji Tabuchi, MD, Zenya Ito, MD, Shigeki Tsuji, MD, Akira Hara, MD, Tetsuro Wada, MD, Jun Kusakari, MD", + "title": "Effect of Ketamine, Dextromethorphan, and MK-801 on Cochlear Dysfunction Induced by Transient Ischemia", + "url": "https://doi.org/10.1177/000348940211100107" + } + ], + "status": "Low Risk & Synergy" + }, + "diphenhydramine": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Ketamine has a high likelihood of increasing DPH's deliriant effects at higher dosages and can greatly increase the risk of injury, mania, and psychosis. Medical dosages of both substances are unlikely to cause concern.", + "sources": [ + { + "author": "Bylund, W., Delahanty, L., & Cooper, M.", + "title": "The Case of Ketamine Allergy. Clinical Practice and Cases in Emergency Medicine, 1(4), 323–325. (2017)", + "url": "https://doi.org/10.5811/cpcem.2017.7.34405" + }, + { + "author": "Clark, J. H., Meltzer, E. O., & Naclerio, R. M.", + "title": "Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027. (2025)", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Rosenbaum, S. B., Gupta, V., Patel, P., & Palacios, J. L.", + "title": "Ketamine. In StatPearls. StatPearls Publishing. (2025)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK470357/" + }, + { + "author": "Sicari, V., Patel, P., & Zabbo, C. P.", + "title": "Diphenhydramine. In StatPearls. StatPearls Publishing. (2025)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + } + ], + "status": "Dangerous" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "dox": { + "note": "Ketamine and psychedelics tend to potentiate each other - go slowly.", + "status": "Low Risk & Synergy" + }, + "ghb/gbl": { + "note": "Both substances cause ataxia and bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.", + "status": "Dangerous" + }, + "lithium": { + "note": "Lithium may enhance and prolong the antidepressant effects of ketamine.", + "sources": [ + { + "author": "Costi, S., Soleimani, L., Glasgow, A., Brallier, J., Spivack, J., Schwartz, J., Levitch, C. F., Richards, S., Hoch, M., Stade, E. C., Welch, A., Collins, K. A., Feder, A., Iosifescu, D. V., Charney, D. S., & Murrough, J. W. (2019)", + "title": "Lithium continuation therapy following ketamine in patients with treatment resistant unipolar depression: a randomized controlled trial. Neuropsychopharmacology, 44(10), 1812–1819.", + "url": "https://doi.org/10.1038/s41386-019-0365-0" + }, + { + "author": "Diazgranados, N., Ibrahim, L., Brutsche, N. E., Newberg, A., Kronstein, P., Khalife, S., Kammerer, W. A., Quezado, Z., Luckenbaugh, D. A., Salvadore, G., Machado-Vieira, R., Manji, H. K., & Zarate, C. A. (2010)", + "title": "A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression. Archives of General Psychiatry, 67(8), 793.", + "url": "https://doi.org/10.1001/archgenpsychiatry.2010.90" + }, + { + "author": "Price, J. B., Yates, C. G., Morath, B. A., Van De Wakker, S. K., Yates, N. J., Butters, K., Frye, M. A., McGee, S. L., & Tye, S. J. (2021)", + "title": "Lithium augmentation of ketamine increases insulin signaling and antidepressant-like active stress coping in a rodent model of treatment-resistant depression. Translational Psychiatry, 11(1), 1–12.", + "url": "https://doi.org/10.1038/s41398-021-01716-w" + }, + { + "author": "Scheuing, L., Chiu, C.-T., Liao, H.-M., & Chuang, D.-M. (2015)", + "title": "Antidepressant mechanism of ketamine: perspective from preclinical studies. Frontiers in Neuroscience, 9.", + "url": "https://doi.org/10.3389/fnins.2015.00249" + }, + { + "author": "Toulany, J., Cunningham, J. E. A., & Nunes, A. (2025)", + "title": "Overlap and Divergence in Ketamine and Lithium Response in Bipolar Disorder: A Scoping Review. Pharmaceuticals, 18(11), 1662.", + "url": "https://doi.org/10.3390/ph18111662" + }, + { + "author": "Wilkowska, A., Szałach, Ł., & Cubała, W. J. (2020)", + "title": "Ketamine in Bipolar Disorder: A Review. Neuropsychiatric Disease and Treatment, 16, 2707–2717.", + "url": "https://doi.org/10.2147/NDT.S282208" + } + ], + "status": "Low Risk & No Synergy" + }, + "lsd": { + "status": "Low Risk & Synergy" + }, + "maois": { + "note": "MAO-B inhibitors appear to increase the potency of Ketamine. MAO-A inhbitors have some negative reports associated with the combination but there isn't much information available", + "status": "Caution" + }, + "mdma": { + "note": "No unexpected interactions, though likely to increase blood pressure but not an issue with sensible doses. Moving around on high doses of this combination may be ill advised due to risk of physical injury.", + "status": "Low Risk & Synergy" + }, + "mescaline": { + "status": "Low Risk & Synergy" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "status": "Low Risk & Synergy" + }, + "nbomes": { + "status": "Low Risk & Synergy" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "note": "Both substances bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.", + "status": "Dangerous" + }, + "pcp": { + "status": "Low Risk & Synergy" + }, + "pregabalin": { + "note": "Pregabalin and ketamine may synergize and increase each other's negative side effects such as nausea, dizziness, and loss of consciousness. Caution is advised for beyond medical dosages due to seizure concerns, and medical dosages for individuals with higher risk seizure profiles and or behavior.", + "sources": [ + { + "author": "Anwar, S., Cooper, J., Rahman, J., Sharma, C., & Langford, R. (2019)", + "title": "Prolonged Perioperative Use of Pregabalin and Ketamine to Prevent Persistent Pain after Cardiac Surgery. Anesthesiology, 131(1), 119–131.", + "url": "https://doi.org/10.1097/ALN.0000000000002751" + }, + { + "author": "Arendt-Nielsen, L., Mansikka, H., Staahl, C., Rees, H., Tan, K., Smart, T. S., Monhemius, R., Suzuki, R., & Drewes, A. M. (2011)", + "title": "A Translational Study of the Effects of Ketamine and Pregabalin on Temporal Summation of Experimental Pain. Regional Anesthesia & Pain Medicine, 36(6), 585–591.", + "url": "https://doi.org/10.1097/AAP.0b013e31822b0db0" + }, + { + "author": "Az, A., & Doğan, Y. (2024)", + "title": "Unexpected consequences: A case of ketamine‑induced seizure in procedural sedation. Turkish Journal of Emergency Medicine, 24(4), 259–261.", + "url": "https://doi.org/10.4103/tjem.tjem_67_24" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben‐Menachem, E. (2004)", + "title": "Pregabalin Pharmacology and Its Relevance to Clinical Practice. Epilepsia, 45(s6), 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures: A historical-controlled trial. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N., & Livingston, J. (2006)", + "title": "Aggravation of epilepsy by anti‐epileptic drugs. Developmental Medicine & Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kim, J. H., Lee, C. K., Yu, S. H., Min, B. D., Chung, C. E., & Kim, D. C. (2021)", + "title": "Ketamine-induced generalized convulsive seizure during procedural sedation. Archives of Craniofacial Surgery, 22(2), 119–121.", + "url": "https://doi.org/10.7181/acfs.2021.00094" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Martinez, V., Cymerman, A., Ben Ammar, S., Fiaud, J. F., Rapon, C., Poindessous, F., Judet, T., Chauvin, M., Bouhassira, D., Sessler, D., Mazoit, X., & Fletcher, D. (2014)", + "title": "The analgesic efficiency of combined pregabalin and ketamine for total hip arthroplasty: a randomised, double‐blind, controlled study. Anaesthesia, 69(1), 46–52.", + "url": "https://doi.org/10.1111/anae.12495" + }, + { + "author": "Shehata, I. M., Kohaf, N. A., ElSayed, M. W., Latifi, K., Aboutaleb, A. M., & Kaye, A. D. (2024)", + "title": "Ketamine: Pro or antiepileptic agent? A systematic review. Heliyon, 10(2), e24433.", + "url": "https://doi.org/10.1016/j.heliyon.2024.e24433" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Zhou, Y., Sun, W., Fu, Y., Wang, J., Fan, J., Liang, Y., Jia, W., & Han, R. (2024)", + "title": "Effect of esketamine combined with pregabalin on acute postsurgical pain in patients who underwent resection of spinal neoplasms: a randomized controlled trial. Pain, 165(9), e96–e105.", + "url": "https://doi.org/10.1097/j.pain.0000000000003211" + } + ], + "status": "Caution" + }, + "ssris": { + "status": "Low Risk & No Synergy" + }, + "tramadol": { + "status": "Dangerous" + } + }, + "lithium": { + "2c-t-x": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + } + ], + "status": "Dangerous" + }, + "2c-x": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + } + ], + "status": "Dangerous" + }, + "cocaine": { + "note": "Lithium may inhibit some of the recreational effects of cocaine.", + "sources": [ + { + "author": "Flemenbaum, A.", + "title": "Antagonism of behavioral effects of cocaine by lithium. (1977)", + "url": "https://doi.org/10.1016/0091-3057(77)90015-6" + }, + { + "author": "Cronson, A. J., & Flemenbaum, A.", + "title": "Antagonism of Cocaine Highs by Lithium. (1981)", + "url": "https://doi.org/10.1007/978-1-4684-3614-3_132" + } + ], + "status": "Low Risk & Decrease" + }, + "dextromethorphan": { + "note": "There is a risk of serotonin syndrome when combining Lithium with DXM.", + "sources": [ + { + "author": "Lenox, R. H., & Hahn, C. G.", + "title": "Overview of the mechanism of action of lithium in the brain: fifty-year update (2000)", + "url": "https://pubmed.ncbi.nlm.nih.gov/10826655/" + }, + { + "author": "Shahani, L.", + "title": "Venlafaxine Augmentation With Lithium Leading to Serotonin Syndrome (2012)", + "url": "https://doi.org/10.1176/appi.neuropsych.11080196" + }, + { + "author": "DeBattista, C., Sofuoglu, M., & Schatzberg, A. F.", + "title": "Serotonergic synergism: the risks and benefits of combining the selective serotonin reuptake inhibitors with other serotonergic drugs (1998)", + "url": "https://doi.org/10.1016/s0006-3223(98)00161-9" + }, + { + "author": "Massot, O.", + "title": "5-HT1B Receptors: A Novel Target for Lithium: Possible Involvement in Mood Disorders (1999)", + "url": "https://doi.org/10.1016/S0893-133X(99)00042-1" + }, + { + "author": "Navarro, A., Perry, C., & Bobo, W. V.", + "title": "A case of serotonin syndrome precipitated by abuse of the anticough remedy dextromethorphan in a bipolar patient treated with fluoxetine and lithium. (2006)", + "url": "https://doi.org/10.1016/j.genhosppsych.2005.06.008" + } + ], + "status": "Dangerous" + }, + "diphenhydramine": { + "note": "There is a concern of serotonin syndrome at higher dosages of this combination. Caution is recommended in restricting diphenhydramine to medical dosages (25-50mg). Lithium and diphenhydramine both have concerns of QT prolongation which may be increased when taken in combination; risks increase due to a variety of factors such as the health of the user and drug dosages. Additionally, the combination may increase each drug's side effects, such as dizziness and loss of consciousness.", + "sources": [ + { + "author": "Clark, J. H., Meltzer, E. O., & Naclerio, R. M.", + "title": "Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027. (2025)", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Crouch, M. A., Limon, L., & Cassano, A. T.", + "title": "Clinical Relevance and Management of Drug‐Related QT Interval Prolongation. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 23(7), 881–908. (2003)", + "url": "https://doi.org/10.1592/phco.23.7.881.32730" + }, + { + "author": "Farzam, K., & Tivakaran, V. S.", + "title": "QT Prolonging Drugs. In StatPearls. StatPearls Publishing. (2025)", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK534864/" + }, + { + "author": "Finley, P. R.", + "title": "Drug Interactions with Lithium: An Update. Clinical Pharmacokinetics, 55(8), 925–941. (2016)", + "url": "https://doi.org/10.1007/s40262-016-0370-y" + }, + { + "author": "Hawley, C. J., Loughlin, P. J., Quick, S. J., Gale, T. M., Sivakumaran, T., Hayes, J., & McPhee, S.", + "title": "Efficacy, safety and tolerability of combined administration of lithium and selective serotonin reuptake inhibitors: a review of the current evidence. International Clinical Psychopharmacology, 15(4), 197–206. (2000)", + "url": "https://doi.org/10.1097/00004850-200015040-00002" + }, + { + "author": "Husain, Z., Hussain, K., Nair, R., & Steinman, R.", + "title": "Diphenhydramine induced QT prolongation and torsade de pointes: An uncommon effect of a common drug. Cardiology Journal, 17(5), 509–511. (2010)", + "url": "https://journals.viamedica.pl/cardiology_journal/article/view/21341" + }, + { + "author": "Khan, S., Saud, S., Khan, I., Asif, M., Ismail, O., Salam, A., Yang, T. J., & Norville, K. J.", + "title": "Serotonin Syndrome Presenting with Concomitant Tramadol and Diphenhydramine Use: A Case Report of an Unlikely Side-Effect. Cureus. (2018)", + "url": "https://doi.org/10.7759/cureus.2421" + }, + { + "author": "Massot, O., Rousselle, J.-C., Fillion, M.-P., Januel, D., Plantefol, M., & Fillion, G.", + "title": "5-HT1B Receptors: A Novel Target for Lithium: Possible Involvement in Mood Disorders. Neuropsychopharmacology, 21(4), 530–541. (1999)", + "url": "https://doi.org/10.1016/S0893-133X(99)00042-1" + }, + { + "author": "Mehta, N., & Vannozzi, R.", + "title": "Lithium‐induced electrocardiographic changes: A complete review. Clinical Cardiology, 40(12), 1363–1367. (2017)", + "url": "https://doi.org/10.1002/clc.22822" + }, + { + "author": "Müller-Oerlinghausen, B.", + "title": "Drug Interactions with Lithium: A Guide for Clinicians. CNS Drugs, 11(1), 41–48. (1999)", + "url": "https://doi.org/10.2165/00023210-199911010-00004" + }, + { + "author": "Rosenberg, A. E., Wang, R., & Rosenberg, M. H.", + "title": "Serotonin Syndrome Associated With High-dose Diphenhydramine Use Complicating Abdominoplasty and Mastopexy. Plastic and Reconstructive Surgery - Global Open, 13(3), e6634. (2025)", + "url": "https://doi.org/10.1097/GOX.0000000000006634" + }, + { + "author": "Truedson, P., Ott, M., Lindmark, K., Ström, M., Maripuu, M., Lundqvist, R., & Werneke, U.", + "title": "Effects of Toxic Lithium Levels on ECG—Findings from the LiSIE Retrospective Cohort Study. Journal of Clinical Medicine, 11(19), 5941. (2022)", + "url": "https://doi.org/10.3390/jcm11195941" + } + ], + "status": "Caution" + }, + "dmt": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + } + ], + "status": "Dangerous" + }, + "dox": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + } + ], + "status": "Dangerous" + }, + "ketamine": { + "note": "Lithium may enhance and prolong the antidepressant effects of ketamine.", + "sources": [ + { + "author": "Costi, S., Soleimani, L., Glasgow, A., Brallier, J., Spivack, J., Schwartz, J., Levitch, C. F., Richards, S., Hoch, M., Stade, E. C., Welch, A., Collins, K. A., Feder, A., Iosifescu, D. V., Charney, D. S., & Murrough, J. W. (2019)", + "title": "Lithium continuation therapy following ketamine in patients with treatment resistant unipolar depression: a randomized controlled trial. Neuropsychopharmacology, 44(10), 1812–1819.", + "url": "https://doi.org/10.1038/s41386-019-0365-0" + }, + { + "author": "Diazgranados, N., Ibrahim, L., Brutsche, N. E., Newberg, A., Kronstein, P., Khalife, S., Kammerer, W. A., Quezado, Z., Luckenbaugh, D. A., Salvadore, G., Machado-Vieira, R., Manji, H. K., & Zarate, C. A. (2010)", + "title": "A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression. Archives of General Psychiatry, 67(8), 793.", + "url": "https://doi.org/10.1001/archgenpsychiatry.2010.90" + }, + { + "author": "Price, J. B., Yates, C. G., Morath, B. A., Van De Wakker, S. K., Yates, N. J., Butters, K., Frye, M. A., McGee, S. L., & Tye, S. J. (2021)", + "title": "Lithium augmentation of ketamine increases insulin signaling and antidepressant-like active stress coping in a rodent model of treatment-resistant depression. Translational Psychiatry, 11(1), 1–12.", + "url": "https://doi.org/10.1038/s41398-021-01716-w" + }, + { + "author": "Scheuing, L., Chiu, C.-T., Liao, H.-M., & Chuang, D.-M. (2015)", + "title": "Antidepressant mechanism of ketamine: perspective from preclinical studies. Frontiers in Neuroscience, 9.", + "url": "https://doi.org/10.3389/fnins.2015.00249" + }, + { + "author": "Toulany, J., Cunningham, J. E. A., & Nunes, A. (2025)", + "title": "Overlap and Divergence in Ketamine and Lithium Response in Bipolar Disorder: A Scoping Review. Pharmaceuticals, 18(11), 1662.", + "url": "https://doi.org/10.3390/ph18111662" + }, + { + "author": "Wilkowska, A., Szałach, Ł., & Cubała, W. J. (2020)", + "title": "Ketamine in Bipolar Disorder: A Review. Neuropsychiatric Disease and Treatment, 16, 2707–2717.", + "url": "https://doi.org/10.2147/NDT.S282208" + } + ], + "status": "Low Risk & No Synergy" + }, + "lsd": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + }, + { + "author": "Edwards, C., Van Gerpen, S., & Anand, V.", + "title": "New-Onset Seizures in an Adolescent Following Use of LSD while on Low-Dose Lithium Therapy: A Case Study. (2024)", + "url": "https://doi.org/10.1177%2F1941874414528939" + } + ], + "status": "Dangerous" + }, + "mdma": { + "note": "High risk of serotonin syndrome", + "sources": [ + { + "author": "Lokesh Shahani", + "title": "Venlafaxine Augmentation With Lithium Leading to Serotonin Syndrome", + "url": "https://doi.org/10.1176/appi.neuropsych.11080196" + }, + { + "author": "Charles DeBattista, Mehmet Sofuoglu, and Alan F. Schatzberg", + "title": "Serotonergic Synergism: The Risks and Benefits of Combining the Selective Serotonin Reuptake Inhibitors with Other Serotonergic Drugs", + "url": "https://www.biologicalpsychiatryjournal.com/article/S0006-3223(98)00161-9/pdf" + }, + { + "author": "Olivier Massot Ph.D, Jean-Claude Rousselle Ph.D, Marie-Paule Fillion MSc, Dominique Januel MD, Mathieu Plantefol MSc & Gilles Fillion Ph.D ", + "title": "5-HT1B Receptors: A Novel Target for Lithium: Possible Involvement in Mood Disorders", + "url": "https://doi.org/10.1016/S0893-133X(99)00042-1" + }, + { + "author": "Philip J. Cowen", + "title": "New drugs, old problems: Revisiting… Pharmacological management of treatment-resistant depression", + "url": "https://doi.org/10.1192/apt.11.1.19" + } + ], + "status": "Dangerous" + }, + "mescaline": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + } + ], + "status": "Dangerous" + }, + "mushrooms": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + } + ], + "status": "Dangerous" + }, + "mxe": { + "note": "There is a risk of serotonin syndrome when combining Lithium with MXE, as Lithium can induce serotonin syndrome in conjunction with other serotonergic drugs, and MXE has shown a notable affinity for the serotonin transporter.", + "sources": [ + { + "author": "Lenox, R. H., & Hahn, C. G.", + "title": "Overview of the mechanism of action of lithium in the brain: fifty-year update (2000)", + "url": "https://pubmed.ncbi.nlm.nih.gov/10826655/" + }, + { + "author": "Shahani, L.", + "title": "Venlafaxine Augmentation With Lithium Leading to Serotonin Syndrome (2012)", + "url": "https://doi.org/10.1176/appi.neuropsych.11080196" + }, + { + "author": "DeBattista, C., Sofuoglu, M., & Schatzberg, A. F.", + "title": "Serotonergic synergism: the risks and benefits of combining the selective serotonin reuptake inhibitors with other serotonergic drugs (1998)", + "url": "https://doi.org/10.1016/S0006-3223(98)00161-9" + }, + { + "author": "Massot, O.", + "title": "5-HT1B Receptors: A Novel Target for Lithium: Possible Involvement in Mood Disorders (1999)", + "url": "https://doi.org/10.1016/S0893-133X(99)00042-1" + }, + { + "author": "Roth, B. L., Gibbons, S., Arunotayanun, W., Huang, X.-P., Setola, V., Treble, R., & Iversen, L.", + "title": "The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor (2013)", + "url": "https://doi.org/10.1371/journal.pone.0059334" + }, + { + "author": "Marti, M., Talani, G., Miliano, C., Bilel, S., Biggio, F., Bratzu, J., Diana, M., De Luca, M. A., & Fattore, L.", + "title": "New insights into methoxetamine mechanisms of action: Focus on serotonergic 5-HT2 receptors in pharmacological and behavioral effects in the rat (2021)", + "url": "https://doi.org/10.1016/j.expneurol.2021.113836" + } + ], + "status": "Dangerous" + }, + "nbomes": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + }, + { + "author": "Umemura, Y., Andrew, T. A., Jacobs, V. L., Giustini, A. J., Lewis, L. D., & Filiano, J. J.", + "title": "Fatal 251-NBOMe Intoxication: A New Recreational Risk. (2015)", + "url": "https://doi.org/10.23907/2015.009" + } + ], + "status": "Dangerous" + }, + "nitrous": { + "note": "We are unable to find a report of concerns for CNS depression caused by Lithium.", + "sources": [ + { + "author": "Drugbank", + "title": "Lithium Carbonate", + "url": "https://go.drugbank.com/drugs/DB14509" + } + ], + "status": "Low Risk & No Synergy" + }, + "ssris": { + "note": "This interaction is used in medical settings without reported issues. If this combination is taken, caution would be recommended if any other drugs are planned to be taken on top of these that may have serotonergic activity.", + "sources": [ + { + "author": "Finley, P. R.", + "title": "Drug Interactions with Lithium: An Update. (2016)", + "url": "https://doi.org/10.1007/s40262-016-0370-y" + }, + { + "author": "Hawley CJ, Loughlin PJ, Quick SJ, Gale TM, Sivakumaran T, Hayes J, McPhee S.", + "title": "Efficacy, safety and tolerability of combined administration of lithium and selective serotonin reuptake inhibitors: a review of the current evidence. (2000)", + "url": "https://doi.org/10.1097/00004850-200015040-00002" + }, + { + "author": "Müller-Oerlinghausen, B.", + "title": "Drug Interactions with Lithium. (1999)", + "url": "https://doi.org/10.2165/00023210-199911010-00004" + }, + { + "author": "Bauer, Michael PhD, MD; Linden, Michael MD; Schaaf, Berthold; Weber, Hans J. MD.", + "title": "Adverse Events and Tolerability of the Combination of Fluoxetine/Lithium Compared With Fluoxetine. (1996)", + "url": "https://doi.org/10.1097/00004714-199604000-00005" + } + ], + "status": "Low Risk & No Synergy" + }, + "tramadol": { + "note": "Tramadol and Lithium both increase the risk of seizures and serotonin syndrome.", + "sources": [ + { + "author": "Steven C. Julius, Richard P. Brenner", + "title": "Myoclonic seizures with lithium", + "url": "https://doi.org/10.1016/0006-3223(87)90026-6" + }, + { + "author": "Charles DeBattista, Mehmet Sofuoglu, and Alan F. Schatzberg", + "title": "Serotonergic Synergism: The Risks and Benefits of Combining the Selective Serotonin Reuptake Inhibitors with Other Serotonergic Drugs", + "url": "https://doi.org/10.1016/s0006-3223(98)00161-9" + }, + { + "author": "Massot, O., Rousselle, JC., Fillion, MP. et al.", + "title": "5-HT1B Receptors: A Novel Target for Lithium: Possible Involvement in Mood Disorders", + "url": "https://doi.org/10.1016/S0893-133X(99)00042-1" + }, + { + "author": "Sameer Hassamal, Karen Miotto, William Dale, Itai Danovitch ", + "title": "Tramadol: Understanding the Risk of Serotonin Syndrome and Seizures", + "url": "https://doi.org/10.1016/j.amjmed.2018.04.025" + }, + { + "author": "Boostani R, Derakhshan S.", + "title": "Tramadol induced seizure: A 3-year study.", + "url": "https://pubmed.ncbi.nlm.nih.gov/24009919/" + }, + { + "author": "Lagard, C.; Vodovar, D.; Chevillard, L.; Callebert, J.; Caillé, F.; Pottier, G.; Liang, H.; Risède, P.; Tournier, N.; Mégarbane, B.", + "title": "Investigation of the Mechanisms of Tramadol-Induced Seizures in Overdose in the Rat ", + "url": "https://doi.org/10.3390/ph15101254 " + }, + { + "author": "Sansone RA, Sansone LA.", + "title": "Tramadol", + "url": "https://pubmed.ncbi.nlm.nih.gov/19724727" + } + ], + "status": "Dangerous" + } + }, + "lsd": { + "2c-t-x": { + "status": "Low Risk & Synergy" + }, + "2c-x": { + "status": "Low Risk & Synergy" + }, + "5-meo-xxt": { + "status": "Low Risk & Synergy" + }, + "alcohol": { + "status": "Low Risk & Decrease" + }, + "amphetamines": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "amt": { + "status": "Low Risk & Synergy" + }, + "benzodiazepines": { + "status": "Low Risk & Decrease" + }, + "caffeine": { + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "cocaine": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "dextromethorphan": { + "status": "Low Risk & Synergy" + }, + "diphenhydramine": { + "note": "At 25-50mg, DPH may assist with side effects of the LSD such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and LSD is cautioned against. LSD is likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma. LSD and DPH at recreational dosages have additional cardiac concerns such as vasoconstriction, tachycardia, hypertension, which in combination may be exacerbated.", + "sources": [ + { + "author": "Marraffa, J. M. (2014)", + "title": "Drugs of Abuse. In Encyclopedia of Toxicology (pp. 248–251). Elsevier.", + "url": "https://doi.org/10.1016/B978-0-12-386454-3.00684-9" + }, + { + "author": "Passie, T., Halpern, J. H., Stichtenoth, D. O., Emrich, H. M., & Hintzen, A. (2008)", + "title": "The Pharmacology of Lysergic Acid Diethylamide: A Review. CNS Neuroscience & Therapeutics, 14(4), 295–314.", + "url": "https://doi.org/10.1111/j.1755-5949.2008.00059.x" + }, + { + "author": "Schaefer, T. S., Patel, P., & Zito, P. M. (2025)", + "title": "Antiemetic Histamine H1 Receptor Blockers. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK533003/" + }, + { + "author": "Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)", + "title": "Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.", + "url": "https://doi.org/10.3389/fpsyt.2021.657397" + }, + { + "author": "The drugs of misuse. (2009)", + "title": "In Auricular Acupuncture & Addiction (pp. 93–135). Elsevier.", + "url": "https://doi.org/10.1016/B978-0-443-06885-0.50018-5" + }, + { + "author": "Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)", + "title": "Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.", + "url": "https://doi.org/10.1016/j.jaip.2022.07.018" + } + ], + "status": "Caution" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "dox": { + "status": "Low Risk & Synergy" + }, + "ghb/gbl": { + "status": "Low Risk & Decrease" + }, + "ketamine": { + "status": "Low Risk & Synergy" + }, + "lithium": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + }, + { + "author": "Edwards, C., Van Gerpen, S., & Anand, V.", + "title": "New-Onset Seizures in an Adolescent Following Use of LSD while on Low-Dose Lithium Therapy: A Case Study. (2024)", + "url": "https://doi.org/10.1177%2F1941874414528939" + } + ], + "status": "Dangerous" + }, + "maois": { + "status": "Low Risk & Decrease" + }, + "mdma": { + "status": "Low Risk & Synergy" + }, + "mephedrone": { + "note": "The anxiogenic and focusing effects of stimulants increase the chance of unpleasant thought loops, in addition to the possible negative side effects of coming down from said stimulant while on a psychedelic. In extreme cases, stimulants, especially in combination can result in severe vasoconstriction, tachycardia, hypertension, and heart failure.", + "sources": [ + { + "author": "Gregory C. Hadlock, Katy M. Webb, Lisa M. McFadden, Pei Wen Chu, Jonathan D. Ellis, Scott C. Allen, David M. Andrenyak, Paula L. Vieira-Brock, Christopher L. German, Kevin M. Conrad, Amanda J. Hoonakker, James W. Gibb, Diana G. Wilkins, Glen R. Hanson and Annette E. Fleckenstein", + "title": "4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse", + "url": "https://doi.org/10.1124/jpet.111.184119" + }, + { + "author": "Michael H Baumann, Mario A Ayestas Jr, John S Partilla, Jacqueline R Sink, Alexander T Shulgin, Paul F Daley, Simon D Brandt, Richard B Rothman, Arnold E Ruoho, Nicholas V Cozzi", + "title": "The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue ", + "url": "https://doi.org/10.1038/npp.2011.304" + }, + { + "author": "MJ Wright, Jr, SA Vandewater, D Angrish, 2 TJ Dickerson, and MA Taffe", + "title": "Mephedrone (4-methylmethcathinone) and d-methamphetamine improve visuospatial associative memory, but not spatial working memory, in rhesus macaques", + "url": "https://doi.org/10.1111%2Fj.1476-5381.2012.02091.x" + }, + { + "author": "J Kehr, F Ichinose, S Yoshitake, M Goiny,1, T Sievertsson, F Nyberg, and T Yoshitake", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats", + "url": "https://doi.org/10.1111%2Fj.1476-5381.2011.01499.x" + }, + { + "author": "Jolanta Opacka-Juffry, Thomas Pinnell, Nisha Patel, Melissa Bevan, Meghan Meintel, Colin Davidson", + "title": "Stimulant mechanisms of cathinones - effects of mephedrone and other cathinones on basal and electrically evoked dopamine efflux in rat accumbens brain slices ", + "url": "https://doi.org/10.1016/j.pnpbp.2014.04.009" + }, + { + "author": "Schmid Y, Enzler F, Gasser P, Grouzmann E, Preller KH, Vollenweider FX, Brenneisen R, Müller F, Borgwardt S, Liechti ME", + "title": "Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects ", + "url": "https://doi.org/10.1016/j.biopsych.2014.11.015" + }, + { + "author": "Holze F, Vizeli P, Müller F, Ley L, Duerig R, Varghese N, Eckert A, Borgwardt S, Liechti ME", + "title": "Distinct acute effects of LSD, MDMA, and D-amphetamine in healthy subjects ", + "url": "https://doi.org/10.1038/s41386-019-0569-3" + }, + { + "author": "Kenneth J Broadley", + "title": "The vascular effects of trace amines and amphetamines ", + "url": "https://doi.org/10.1016/j.pharmthera.2009.11.005" + }, + { + "author": "James R. Docherty, Hadeel A. Alsufyani", + "title": "Cardiovascular and temperature adverse actions of stimulants", + "url": "https://doi.org/10.1111/bph.15465" + }, + { + "author": "James R. Docherty DSc, Hadeel A. Alsufyani MB, PhD", + "title": "Pharmacology of Drugs Used as Stimulants", + "url": "https://doi.org/10.1002/jcph.1918" + }, + { + "author": "Breier Y, Azrak E, Banks W, Kushmakov R, Aleshinskaya I", + "title": "Management of New Onset Amphetamine-Induced Acute Decompensated Heart Failure in a Young Adult: Case Report", + "url": "https://doi.org/10.7759%2Fcureus.43854" + } + ], + "status": "Caution" + }, + "mescaline": { + "status": "Low Risk & Synergy" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "status": "Low Risk & Synergy" + }, + "nbomes": { + "sources": [ + { + "author": "Umemura, Y., Andrew, T. A., Jacobs, V. L., Giustini, A. J., Lewis, L. D., & Filiano, J. J.", + "title": "Fatal 251-NBOMe Intoxication: A New Recreational Risk. Academic Forensic Pathology", + "url": "https://doi.org/10.23907/2015.009" + } + ], + "status": "Low Risk & Synergy" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "status": "Low Risk & No Synergy" + }, + "pcp": { + "status": "Low Risk & Synergy" + }, + "pregabalin": { + "note": "Caution should be given due to LSD’s stimulating effects and pregabalin’s seizure concerns at higher dosages. Pregabalin may reduce the vasoconstriction, anxiety, and other side effects of LSD. Additionally, Pregabalin may increase LSD’s inhibition and risk of injury.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Baquiran, M., Keyes, D., & Al Khalili, Y. (2025)", + "title": "Lysergic Acid Diethylamide Toxicity. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK553216/" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Soto-Angona, Ó., Fortea, A., Fortea, L., Martínez-Ramírez, M., Santamarina, E., López, F. J. G., Knudsen, G. M., & Ona, G. (2024)", + "title": "Do classic psychedelics increase the risk of seizures? A scoping review. European Neuropsychopharmacology, 85, 35–42.", + "url": "https://doi.org/10.1016/j.euroneuro.2024.05.002" + } + ], + "status": "Caution" + }, + "ssris": { + "status": "Low Risk & Decrease" + }, + "tramadol": { + "note": "Tramadol is well known to lower seizure threshold and psychedelics also cause occasional seizures.", + "status": "Unsafe" + } + }, + "maois": { + "2c-t-x": { + "note": "MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably, which could be dangerous given the unpredictability of the 2C-T-x series", + "status": "Caution" + }, + "2c-x": { + "note": "MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably", + "status": "Caution" + }, + "5-meo-xxt": { + "status": "Dangerous" + }, + "alcohol": { + "note": "Tyramine found in many alcoholic beverages can have dangerous reactions with MAOIs, causing an increase in blood pressure.", + "status": "Unsafe" + }, + "amphetamines": { + "note": "MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably. MAO-A inhibitors with amphetamine can lead to hypertensive crises.", + "status": "Dangerous" + }, + "amt": { + "note": "aMT is an MAOI on its own. Using enzyme inhibitors can greatly reduce predictability of effects.", + "status": "Dangerous" + }, + "benzodiazepines": { + "status": "Low Risk & Synergy" + }, + "caffeine": { + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "status": "Low Risk & Synergy" + }, + "cocaine": { + "note": "This combination is poorly explored", + "status": "Dangerous" + }, + "dextromethorphan": { + "note": "High risk of serotonin syndrome", + "status": "Dangerous" + }, + "diphenhydramine": { + "note": "There is a significant risk of serotonin syndrome with this combination. Monoamine oxidase A inhibitors may extend and increase the anticholinergic effects of DPH. The combination increases each other’s side effects, such as drowsiness, dizziness, dry mouth, and headaches. Medical dosages are not reported to be of concern.", + "sources": [ + { + "author": "Adawi Awdish, R. L., Whitmill, M., Coba, V., & Killu, K. (2008)", + "title": "Serotonin Reuptake Inhibition by Diphenhydramine and concomitant Linezolid use can result in Serotonin Syndrome Chest, 134(4), 4C.", + "url": "https://doi.org/10.1378/chest.134.4_MeetingAbstracts.c4002" + }, + { + "author": "Clark, J. H., Meltzer, E. O., & Naclerio, R. M. (2025)", + "title": "Diphenhydramine: It is time to say a final goodbye. The World Allergy Organization Journal, 18(2), 101027.", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Edinoff, A. N., Swinford, C. R., Odisho, A. S., Burroughs, C. R., Stark, C. W., Raslan, W. A., Cornett, E. M., Kaye, A. M., & Kaye, A. D. (n.d.)", + "title": "Clinically Relevant Drug Interactions with Monoamine Oxidase Inhibitors. Health Psychology Research, 10(4), 39576.", + "url": "https://doi.org/10.52965/001c.39576" + }, + { + "author": "Gillman, P. K. (2005)", + "title": "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity. British Journal of Anaesthesia, 95(4), 434–441.", + "url": "https://doi.org/10.1093/bja/aei210" + }, + { + "author": "Khan, S., Saud, S., Khan, I., Asif, M., Ismail, O., Salam, A., Yang, T. J., & Norville, K. J. (2018)", + "title": "Serotonin Syndrome Presenting with Concomitant Tramadol and Diphenhydramine Use: A Case Report of an Unlikely Side-Effect. Cureus.", + "url": "https://doi.org/10.7759/cureus.2421" + }, + { + "author": "López-Álvarez, J., Sevilla-Llewellyn-Jones, J., & Agüera-Ortiz, L. (2019)", + "title": "Anticholinergic Drugs in Geriatric Psychopharmacology. Frontiers in Neuroscience, 13, 1309.", + "url": "https://doi.org/10.3389/fnins.2019.01309" + }, + { + "author": "Sub Laban, T., & Saadabadi, A. (2025)", + "title": "Monoamine Oxidase Inhibitors (MAOI). In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK539848/" + } + ], + "status": "Unsafe" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "dox": { + "note": "MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably", + "status": "Caution" + }, + "ghb/gbl": { + "status": "Low Risk & Synergy" + }, + "ketamine": { + "note": "MAO-B inhibitors appear to increase the potency of Ketamine. MAO-A inhbitors have some negative reports associated with the combination but there isn't much information available", + "status": "Caution" + }, + "lsd": { + "status": "Low Risk & Decrease" + }, + "mdma": { + "note": "MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably. MAO-A inhibitors with MDMA will lead to hypertensive crises.", + "status": "Dangerous" + }, + "mescaline": { + "status": "Caution" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "note": "MAO-B inhibitors appear to increase the potency of MXE. MAO-A inhbitors have some negative reports associated with the combination but there isn't much information available", + "status": "Unsafe" + }, + "nbomes": { + "note": "MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably", + "status": "Caution" + }, + "nitrous": { + "status": "Low Risk & No Synergy" + }, + "opioids": { + "note": "Coadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe and fatal adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases.", + "status": "Caution" + }, + "pcp": { + "note": "This combination is very poorly explored", + "status": "Dangerous" + }, + "ssris": { + "status": "Dangerous" + }, + "tramadol": { + "status": "Dangerous" + } + }, + "mdma": { + "2c-t-x": { + "status": "Caution" + }, + "2c-x": { + "status": "Low Risk & Synergy" + }, + "5-meo-xxt": { + "note": "Some of the 5-MeO tryptamines are a bit unpredictable and should be mixed with MDMA with care", + "status": "Caution" + }, + "alcohol": { + "note": "The combination of MDMA and alcohol may increase strain on the cardiovascular system and lead to increased alcohol consumption. MDMA may also impair one's ability to recognize their level of drunkenness, leading to increased alcohol consumption and poor decision-making. Alcohol may also increase the risk of dehydration and hyperthermia (increased body temperature) when combined with MDMA.", + "sources": [ + { + "author": "Hamida, S. B., Plute, E., Cosquer, B., Kelche, C., Jones, B. C., & Cassel, J.-C. ", + "title": "Interactions between ethanol and cocaine, amphetamine, or MDMA in the rat: thermoregulatory and locomotor effects. (2008)", + "url": "https://doi.org/10.1007/s00213-007-1007-5" + }, + { + "author": "Ramaekers, J. G., & Kuypers, K. P. C.", + "title": "Acute Effects of 3,4-Methylenedioxymethamphetamine (MDMA) on Behavioral Measures of Impulsivity: Alone and in Combination with Alcohol. (2006)", + "url": "https://doi.org/10.1038/sj.npp.1300894" + }, + { + "author": "Hernández-López, C., Farré, M., Roset, P. N., Menoyo, E., Pizarro, N., Ortuño, J., Torrens, M., Camı́, J., & Torre, R. de la.", + "title": "3,4-Methylenedioxymethamphetamine (Ecstasy) and Alcohol Interactions in Humans: Psychomotor Performance, Subjective Effects, and Pharmacokinetics. (2002)", + "url": "https://doi.org/10.1124/jpet.300.1.236" + }, + { + "author": "van Amsterdam, J., Brunt, T. M., Pierce, M., & van den Brink, W.", + "title": "Hard Boiled: Alcohol Use as a Risk Factor for MDMA-Induced Hyperthermia: a Systematic Review. (2021)", + "url": "https://doi.org/10.1007/s12640-021-00416-z" + } + ], + "status": "Caution" + }, + "amphetamines": { + "note": "This combination of stimulants will increase strain on the heart, may cause some physical discomfort, and has the chance to cause cardiovascular issues. The anxiogenic and focusing effects of stimulants can increase the chance of unpleasant thought loops and make the experience more uncomfortable, this combination raises these chances. Amphetamines will increase the neurotoxic effects of MDMA, in addition to causing further concerns of hyperthermia due to the inherent nature of the combination. It will also raise one's body temperature, also likely making the combination more neurotoxic.", + "sources": [ + { + "author": "Kelly J. Clemens, Iain S. McGregor, Glenn E. Hunt, Jennifer L. Cornish", + "title": "MDMA, methamphetamine and their combination: possible lessons for party drug users from recent preclinical research", + "url": "https://doi.org/10.1080/09595230601036945" + }, + { + "author": "Kelly J. Clemens, Iain S. McGregor, Glenn E. Hunt, Jennifer L. Cornish", + "title": "Repeated weekly exposure to MDMA, methamphetamine or their combination: long-term behavioural and neurochemical effects in rats ", + "url": "https://doi.org/10.1016/j.drugalcdep.2006.06.004" + }, + { + "author": "P. Leon Brown, Eugene A. Kiyatkin", + "title": "Brain hyperthermia induced by MDMA (‘ecstasy’): modulation by environmental conditions", + "url": "https://doi.org/10.1111/j.0953-816X.2004.03453.x" + } + ], + "status": "Caution" + }, + "amt": { + "status": "Dangerous" + }, + "benzodiazepines": { + "status": "Low Risk & Decrease" + }, + "caffeine": { + "note": "Caffeine is not really necessary with MDMA and increases any neurotoxic effects from MDMA", + "status": "Caution" + }, + "cannabis": { + "note": "Large amounts of cannabis may cause strong and somewhat unpredictable experiences in combination with MDMA. Cannabis should be saved for towards the end of the experience if possible.", + "status": "Low Risk & Synergy" + }, + "cocaine": { + "note": "Cocaine blocks some of the desirable effects of MDMA while increasing the risk of heart attack.", + "status": "Caution" + }, + "dextromethorphan": { + "status": "Dangerous" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "dox": { + "note": "The combined stimulating effects of the two can be uncomfortable. Coming down on the MDMA while the DOx is still active can be quite anxiogenic. ", + "status": "Caution" + }, + "ghb/gbl": { + "note": "Large amounts of GHB/GBL may overwhelm the effects of MDMA on the comedown.", + "status": "Caution" + }, + "ketamine": { + "note": "No unexpected interactions, though likely to increase blood pressure but not an issue with sensible doses. Moving around on high doses of this combination may be ill advised due to risk of physical injury.", + "status": "Low Risk & Synergy" + }, + "lithium": { + "note": "High risk of serotonin syndrome", + "sources": [ + { + "author": "Lokesh Shahani", + "title": "Venlafaxine Augmentation With Lithium Leading to Serotonin Syndrome", + "url": "https://doi.org/10.1176/appi.neuropsych.11080196" + }, + { + "author": "Charles DeBattista, Mehmet Sofuoglu, and Alan F. Schatzberg", + "title": "Serotonergic Synergism: The Risks and Benefits of Combining the Selective Serotonin Reuptake Inhibitors with Other Serotonergic Drugs", + "url": "https://www.biologicalpsychiatryjournal.com/article/S0006-3223(98)00161-9/pdf" + }, + { + "author": "Olivier Massot Ph.D, Jean-Claude Rousselle Ph.D, Marie-Paule Fillion MSc, Dominique Januel MD, Mathieu Plantefol MSc & Gilles Fillion Ph.D ", + "title": "5-HT1B Receptors: A Novel Target for Lithium: Possible Involvement in Mood Disorders", + "url": "https://doi.org/10.1016/S0893-133X(99)00042-1" + }, + { + "author": "Philip J. Cowen", + "title": "New drugs, old problems: Revisiting… Pharmacological management of treatment-resistant depression", + "url": "https://doi.org/10.1192/apt.11.1.19" + } + ], + "status": "Dangerous" + }, + "lsd": { + "status": "Low Risk & Synergy" + }, + "maois": { + "note": "MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably. MAO-A inhibitors with MDMA will lead to hypertensive crises.", + "status": "Dangerous" + }, + "mephedrone": { + "note": "Risk of serotonin syndrome as both drugs raise serotonin levels. Stimulants also increase the neurotoxic effects of MDMA, in addition to concerns of high blood pressure and unnecessary strain on the heart. As well as potentially causing anxiety and greater physical discomfort due to the combination.", + "sources": [ + { + "author": "J Kehr, F Ichinose, S Yoshitake, M Goiny, T Sievertsson, F Nyberg, T Yoshitake", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Gregory C. Hadlock, Katy M. Webb, Lisa M. McFadden, Pei Wen Chu, Jonathan D. Ellis, Scott C. Allen, David M. Andrenyak, Paula L. Vieira-Brock, Christopher L. German, Kevin M. Conrad, Amanda J. Hoonakker, James W. Gibb, Diana G. Wilkins, Glen R. Hanson and Annette E. Fleckenstein", + "title": "4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse", + "url": "https://doi.org/10.1124/jpet.111.184119 " + }, + { + "author": "Gough B, Ali SF, Slikker W Jr, Holson RR. ", + "title": "Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on monoamines in rat caudate. (1991)", + "url": "https://doi.org/10.1016/0091-3057(91)90137-q" + }, + { + "author": "Schmidt CJ, Levin JA, Lovenberg W. ", + "title": "In vitro and in vivo neurochemical effects of methylenedioxymethamphetamine on striatal monoaminergic systems in the rat brain. (1987)", + "url": "https://doi.org/10.1016/0006-2952(87)90729-5" + }, + { + "author": "Bankson MG, Cunningham KA.", + "title": "3,4-Methylenedioxymethamphetamine (MDMA) as a unique model of serotonin receptor function and serotonin-dopamine interactions. (2001)", + "url": "https://pubmed.ncbi.nlm.nih.gov/11356903/" + }, + { + "author": "A.C. Parrott", + "title": "Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity (2002)", + "url": "https://doi.org/10.1016/S0091-3057(01)00711-0" + }, + { + "author": "Lisa H. Gold & George F. Koob ", + "title": "MDMA produces stimulant-like conditioned locomotor activity. (1989)", + "url": "https://doi.org/10.1007/BF00445556" + }, + { + "author": "Meng H, Cao J, Kang J, Ying X, Ji J, Reynolds W, Rampe D.", + "title": "Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat ", + "url": "https://doi.org/10.1016/j.toxlet.2011.10.010" + } + ], + "status": "Dangerous" + }, + "mescaline": { + "status": "Low Risk & Synergy" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "note": "There have been reports of risky serotonergic interactions when the two are taken at the same time, but MXE taken to the end of an MDMA experience does not appear to cause the same issues.", + "status": "Caution" + }, + "nbomes": { + "status": "Caution" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "status": "Low Risk & No Synergy" + }, + "pcp": { + "note": "This combination can easily lead to hypermanic states", + "status": "Unsafe" + }, + "pregabalin": { + "note": "There is a significant risk of seizures from this combination. Amphetamines increase respiration rate allowing for a higher dose of sedatives than normal. If amphetamines wears off first, recreational dosages of pregabalin may overcome the individual and cause respiratory arrest. Both substances at recreational dosages cause strain of the heart and may lead to further dangerous heart complications. Medical dosages are not reported to be a concern", + "sources": [ + { + "author": "Alo, C., & Kioka, M. J. (2024)", + "title": "Rave gone wrong: MDMA- induced medical emergency at electrical daisy carnival. A case report. Toxicology Reports, 13, 101739.", + "url": "https://doi.org/10.1016/j.toxrep.2024.101739" + }, + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Christie, D., Yazar-Klosinski, B., Nosova, E., Kryskow, P., Siu, W., Lessor, D., & Argento, E. (2022)", + "title": "MDMA-assisted therapy is associated with a reduction in chronic pain among people with post-traumatic stress disorder. Frontiers in Psychiatry, 13.", + "url": "https://doi.org/10.3389/fpsyt.2022.939302" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Oskouei, Z., Moshiri, M., Raouf-Rahmati, A., Nemati, A., Bemani Naeini, M., Jomehpour, H., Roohbakhsh, A., Salmasi, Z., & Etemad, L. (2025)", + "title": "Seizures as an Adverse Effect of Pregabalin Consumption: A Systematic Review. Addiction & Health, 17, 1527.", + "url": "https://doi.org/10.34172/ahj.1527" + }, + { + "author": "Rietjens, S. J., Sikma, M. A., Hunault, C. C., De Lange, D. W., & Hondebrink, L. (2022)", + "title": "Pregabalin poisoning: Evaluation of dose‐toxicity relationship. British Journal of Clinical Pharmacology, 88(3), 1288–1297.", + "url": "https://doi.org/10.1111/bcp.15073" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Vollenweider, F. X., Gamma, A., Liechti, M., & Huber, T. (1998)", + "title": "Psychological and cardiovascular effects and short-term sequelae of MDMA (“ecstasy”) in MDMA-naïve healthy volunteers. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 19(4), 241–251.", + "url": "https://doi.org/10.1016/S0893-133X(98)00013-X" + } + ], + "status": "Unsafe" + }, + "ssris": { + "sources": [ + { + "author": "Feduccia, A. A., Jerome, L., Mithoefer, M. C., & Holland, J.", + "title": "Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy.", + "url": "https://doi.org/10.1007/s00213-020-05710-w" + }, + { + "author": "Sarparast, A., Thomas, K., Malcolm, B., & Stauffer, C. S.", + "title": "Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review.", + "url": "https://doi.org/10.1007/s00213-022-06083-y" + }, + { + "author": "Malcolm, B., & Thomas, K. ", + "title": "Serotonin toxicity of serotonergic psychedelics.", + "url": "https://doi.org/10.1007/s00213-021-05876-x" + } + ], + "status": "Low Risk & Decrease" + }, + "tramadol": { + "note": "Tramadol and stimulants both increase the risk of seizures.", + "status": "Dangerous" + } + }, + "mephedrone": { + "caffeine": { + "note": "This combination of stimulants is not generally necessary and may increase strain on the heart, as well as potentially causing anxiety and great physical discomfort. However, individual responses to caffeine can vary significantly, often influenced by factors like habitual versus occasional usage.", + "sources": [ + { + "author": "Mesas AE, Leon-Muñoz LM, Rodriguez-Artalejo F, Lopez-Garcia E", + "title": " The effect of coffee on blood pressure and cardiovascular disease in hypertensive individuals: a systematic review and meta-analysis ", + "url": "https://doi.org/10.3945/ajcn.111.016667" + }, + { + "author": "Nurminen, ML., Niittynen, L., Korpela, R", + "title": "Coffee, caffeine and blood pressure: a critical review", + "url": "https://doi.org/10.1038/sj.ejcn.1600899" + }, + { + "author": "Institute of Medicine (US) Committee on Military Nutrition Research.", + "title": "Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations.", + "url": "https://www.ncbi.nlm.nih.gov/books/NBK223808/" + }, + { + "author": "Baumann MH, Ayestas MA Jr, Partilla JS, Sink JR, Shulgin AT, Daley PF, Brandt SD, Rothman RB, Ruoho AE, Cozzi NV", + "title": "The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue ", + "url": "https://doi.org/10.1038/npp.2011.304" + }, + { + "author": "Wright MJ Jr, Vandewater SA, Angrish D, Dickerson TJ, Taffe MA", + "title": "Mephedrone (4-methylmethcathinone) and d-methamphetamine improve visuospatial associative memory, but not spatial working memory, in rhesus macaques", + "url": "https://doi.org/10.1111%2Fj.1476-5381.2012.02091.x" + }, + { + "author": "Kehr J, Ichinose F, Yoshitake S, Goiny M, Sievertsson T, Nyberg F, Yoshitake T", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats", + "url": "https://doi.org/10.1111%2Fj.1476-5381.2011.01499.x" + } + ], + "status": "Caution" + }, + "dextromethorphan": { + "note": "Risk of serotonin syndrome as both drugs raise serotonin levels. In addition to concerns of high blood pressure and unnecessary strain on the heart. As well as potentially causing anxiety and greater physical discomfort due to the combination.", + "sources": [ + { + "author": "J Kehr, F Ichinose, S Yoshitake, M Goiny, T Sievertsson, F Nyberg, T Yoshitake", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Gregory C. Hadlock, Katy M. Webb, Lisa M. McFadden, Pei Wen Chu, Jonathan D. Ellis, Scott C. Allen, David M. Andrenyak, Paula L. Vieira-Brock, Christopher L. German, Kevin M. Conrad, Amanda J. Hoonakker, James W. Gibb, Diana G. Wilkins, Glen R. Hanson and Annette E. Fleckenstein", + "title": "4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse", + "url": "https://doi.org/10.1124/jpet.111.184119 " + }, + { + "author": "Anna R. Schwartz, Anthony F. Pizon & Daniel E. Brooks", + "title": "Dextromethorphan-induced serotonin syndrome", + "url": "https://doi.org/10.1080/15563650701668625" + }, + { + "author": "DrugBank", + "title": "Dextromethorphan", + "url": "https://go.drugbank.com/drugs/DB00514" + }, + { + "author": "Henderson MG, Fuller RW", + "title": "Dextromethorphan antagonizes the acute depletion of brain serotonin by p-chloroamphetamine and H75/12 in rats", + "url": "https://doi.org/10.1016/0006-8993(92)91144-4" + }, + { + "author": "Reissig CJ, Carter LP, Johnson MW, Mintzer MZ, Klinedinst MA, Griffiths RR", + "title": "High doses of dextromethorphan, an NMDA antagonist, produce effects similar to classic hallucinogens ", + "url": "https://doi.org/10.1007/s00213-012-2680-6" + }, + { + "author": "Meng H, Cao J, Kang J, Ying X, Ji J, Reynolds W, Rampe D.", + "title": "Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat ", + "url": "https://doi.org/10.1016/j.toxlet.2011.10.010" + } + ], + "status": "Dangerous" + }, + "diphenhydramine": { + "note": "There is a high risk of serotonin syndrome at recreational dosages. Both can dull each other's effects, so if one wears off before the other it's possible to overdose due to the lack of counteraction. Medical dosages are reported not to be a concern for the general population. Both substances affect the heart and may lead to further dangerous heart complications at higher dosages. The combination may increase each other's side effects, such as dizziness and drowsiness. At higher dosages, the combination may increase each other's side effects, such as delirium, mania, and psychosis.", + "sources": [ + { + "author": "Clark, J. H., Meltzer, E. O., & Naclerio, R. M.", + "title": "Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027 (2025)", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Ener, R. A., Meglathery, S. B., Decker, W. A. V., & Gallagher, R. M.", + "title": "Serotonin Syndrome and Other Serotonergic Disorders: Table 1. Pain Medicine, 4(1), 63-74 (2003)", + "url": "https://doi.org/10.1046/j.1526-4637.2003.03005.x" + }, + { + "author": "Hadlock, G. C., Webb, K. M., McFadden, L. M., Chu, P. W., Ellis, J. D., Allen, S. C., Andrenyak, D. M., Vieira-Brock, P. L., German, C. L., Conrad, K. M., Hoonakker, A. J., Gibb, J. W., Wilkins, D. G., Hanson, G. R., & Fleckenstein, A. E.", + "title": "4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse. The Journal of Pharmacology and Experimental Therapeutics, 339(2), 530-536 (2011)", + "url": "https://doi.org/10.1124/jpet.111.184119" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T.", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats: Mephedrone increases both DA and 5-HT in rat brain. British Journal of Pharmacology, 164(8), 1949-1958 (2011)", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Meng, H., Cao, J., Kang, J., Ying, X., Ji, J., Reynolds, W., & Rampe, D.", + "title": "Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat. Toxicology Letters, 208(1), 62-68 (2012)", + "url": "https://doi.org/10.1016/j.toxlet.2011.10.010" + }, + { + "author": "Varghese, E., Abate, M. A., Hu, L., Kaplan, J., Kraner, J., Long, D. L., Sorg, M., Mock, A., Greenwald, M., & Andrew, T.", + "title": "Characterization of Diphenhydramine-Related Accidental Overdose Deaths. Academic Forensic Pathology, 5(1), 105-115 (2015)", + "url": "https://doi.org/10.23907/2015.011" + } + ], + "status": "Dangerous" + }, + "dmt": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "sources": [ + { + "author": "Carbonaro, T. M., & Gatch, M. B.", + "title": "Neuropharmacology of N,N-Dimethyltryptamine. Brain Research Bulletin, 126(Pt 1), 74–88 (2016)", + "url": "https://doi.org/10.1016/j.brainresbull.2016.04.016" + }, + { + "author": "Erhorn, S.", + "title": "Dimethyltryptamine. In xPharm: The Comprehensive Pharmacology Reference, 1–4 (2007)", + "url": "https://doi.org/10.1016/B978-008055232-3.62227-5" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T.", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats. British Journal of Pharmacology, 164(8), 1949–1958 (2011)", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Papaseit, E., Moltó, J., Muga, R., Torrens, M., de la Torre, R., & Farré, M.", + "title": "Clinical Pharmacology of the Synthetic Cathinone Mephedrone. In M. H. Baumann, R. A. Glennon, & J. L. Wiley (Eds.), Neuropharmacology of New Psychoactive Substances (NPS): The Science Behind the Headlines, 313–331 (2017)", + "url": "https://doi.org/10.1007/7854_2016_61" + }, + { + "author": "Wood, D. M., Davies, S., Greene, S. L., Button, J., Holt, D. W., Ramsey, J., & Dargan, P. I.", + "title": "Case series of individuals with analytically confirmed acute mephedrone toxicity. Clinical Toxicology, 48(9), 924–927 (2010)", + "url": "https://doi.org/10.3109/15563650.2010.531021" + } + ], + "status": "Low Risk & Synergy" + }, + "dox": { + "note": "The anxiogenic and focusing effects of stimulants increase the chance of unpleasant thought loops, in addition to the possible negative side effects of coming down from said stimulant while on a psychedelic. In extreme cases, stimulants, especially in combination can result in severe vasoconstriction, tachycardia, hypertension, and heart failure.", + "sources": [ + { + "author": "ScienceDirect Topics (n.d.)", + "title": "2,5-Dimethoxy-4-iodoamphetamine - an overview", + "url": "https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/2-5-dimethoxy-4-iodoamphetamine" + }, + { + "author": "Dargan, P. I., Sedefov, R., Gallegos, A., & Wood, D. M. (2011)", + "title": "The pharmacology and toxicology of the synthetic cathinone mephedrone (4‐methylmethcathinone). Drug Testing and Analysis, 3(7–8), 454–463", + "url": "https://doi.org/10.1002/dta.312" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T. (2011)", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats: Mephedrone increases both DA and 5-HT in rat brain. British Journal of Pharmacology, 164(8), 1949–1958", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Trout, K., & Daley, P. F. (2024)", + "title": "The origin of 2,5‐dimethoxy‐4‐methylamphetamine (DOM, STP). Drug Testing and Analysis, 16(12), 1496–1508", + "url": "https://doi.org/10.1002/dta.3667" + } + ], + "status": "Caution" + }, + "ghb/gbl": { + "note": "Both can dull each other's effects, so if one wears off before the other it's possible to overdose due to the lack of counteraction. Both substances affect the heart and may lead to further dangerous heart complications at higher dosages. Additionally, the combination may increase the negative side effects of each other.", + "sources": [ + { + "author": "Aromatario, M., Bottoni, E., Santoni, M., & Ciallella, C.", + "title": "New \"Lethal highs\": A case of a deadly cocktail of GHB and Mephedrone. Forensic Science International, 223(1), e38–e41 (2012)", + "url": "https://doi.org/10.1016/j.forsciint.2012.09.014" + }, + { + "author": "Drugs.ie", + "title": "Drug Combinations \"Mixing Drugs\" - Drug and Alcohol Information and Support in Ireland (2025)", + "url": "https://www.drugs.ie/drugs_info/about_drugs/poly_drug_use1/" + }, + { + "author": "Felmlee, M. A., Morse, B. L., & Morris, M. E.", + "title": "γ-Hydroxybutyric Acid: Pharmacokinetics, Pharmacodynamics, and Toxicology. The AAPS Journal, 23(1), 22 (2021)", + "url": "https://doi.org/10.1208/s12248-020-00543-z" + }, + { + "author": "Galicia, M., Nogue, S., & Miró, O.", + "title": "Liquid ecstasy intoxication: clinical features of 505 consecutive emergency department patients. Emergency Medicine Journal: EMJ, 28(6), 462–466 (2011)", + "url": "https://doi.org/10.1136/emj.2008.068403" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T.", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats. British Journal of Pharmacology, 164(8), 1949–1958 (2011)", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Kozina, L., Grizelj Benussi, M., & Sutara, N.", + "title": "Novel Psychoactive Substances – GHB- and Mephedrone-Induced Delirium Treated with Olanzapine: A Case Report and Literature Review. Medicina Fluminensis, 61(3), 318–326 (2025)", + "url": "https://doi.org/10.21860/medflum2025_332196" + }, + { + "author": "Mayer, F. P., Niello, M., Bulling, S., Zhang, Y.-W., Li, Y., Kudlacek, O., Holy, M., Kooti, F., Sandtner, W., Rudnick, G., Schmid, D., & Sitte, H. H.", + "title": "Mephedrone induces partial release at human dopamine transporters but full release at human serotonin transporters. Neuropharmacology, 240, 109704 (2023)", + "url": "https://doi.org/10.1016/j.neuropharm.2023.109704" + }, + { + "author": "Papaseit, E., Moltó, J., Muga, R., Torrens, M., de la Torre, R., & Farré, M.", + "title": "Clinical Pharmacology of the Synthetic Cathinone Mephedrone. Neuropharmacology of New Psychoactive Substances (NPS): The Science Behind the Headlines, pp. 313–331 (2017)", + "url": "https://doi.org/10.1007/7854_2016_61" + }, + { + "author": "Wood, D. M., Davies, S., Greene, S. L., Button, J., Holt, D. W., Ramsey, J., & Dargan, P. I.", + "title": "Case series of individuals with analytically confirmed acute mephedrone toxicity. Clinical Toxicology, 48(9), 924–927 (2010)", + "url": "https://doi.org/10.3109/15563650.2010.531021" + } + ], + "status": "Caution" + }, + "lsd": { + "note": "The anxiogenic and focusing effects of stimulants increase the chance of unpleasant thought loops, in addition to the possible negative side effects of coming down from said stimulant while on a psychedelic. In extreme cases, stimulants, especially in combination can result in severe vasoconstriction, tachycardia, hypertension, and heart failure.", + "sources": [ + { + "author": "Gregory C. Hadlock, Katy M. Webb, Lisa M. McFadden, Pei Wen Chu, Jonathan D. Ellis, Scott C. Allen, David M. Andrenyak, Paula L. Vieira-Brock, Christopher L. German, Kevin M. Conrad, Amanda J. Hoonakker, James W. Gibb, Diana G. Wilkins, Glen R. Hanson and Annette E. Fleckenstein", + "title": "4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse", + "url": "https://doi.org/10.1124/jpet.111.184119" + }, + { + "author": "Michael H Baumann, Mario A Ayestas Jr, John S Partilla, Jacqueline R Sink, Alexander T Shulgin, Paul F Daley, Simon D Brandt, Richard B Rothman, Arnold E Ruoho, Nicholas V Cozzi", + "title": "The designer methcathinone analogs, mephedrone and methylone, are substrates for monoamine transporters in brain tissue ", + "url": "https://doi.org/10.1038/npp.2011.304" + }, + { + "author": "MJ Wright, Jr, SA Vandewater, D Angrish, 2 TJ Dickerson, and MA Taffe", + "title": "Mephedrone (4-methylmethcathinone) and d-methamphetamine improve visuospatial associative memory, but not spatial working memory, in rhesus macaques", + "url": "https://doi.org/10.1111%2Fj.1476-5381.2012.02091.x" + }, + { + "author": "J Kehr, F Ichinose, S Yoshitake, M Goiny,1, T Sievertsson, F Nyberg, and T Yoshitake", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats", + "url": "https://doi.org/10.1111%2Fj.1476-5381.2011.01499.x" + }, + { + "author": "Jolanta Opacka-Juffry, Thomas Pinnell, Nisha Patel, Melissa Bevan, Meghan Meintel, Colin Davidson", + "title": "Stimulant mechanisms of cathinones - effects of mephedrone and other cathinones on basal and electrically evoked dopamine efflux in rat accumbens brain slices ", + "url": "https://doi.org/10.1016/j.pnpbp.2014.04.009" + }, + { + "author": "Schmid Y, Enzler F, Gasser P, Grouzmann E, Preller KH, Vollenweider FX, Brenneisen R, Müller F, Borgwardt S, Liechti ME", + "title": "Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects ", + "url": "https://doi.org/10.1016/j.biopsych.2014.11.015" + }, + { + "author": "Holze F, Vizeli P, Müller F, Ley L, Duerig R, Varghese N, Eckert A, Borgwardt S, Liechti ME", + "title": "Distinct acute effects of LSD, MDMA, and D-amphetamine in healthy subjects ", + "url": "https://doi.org/10.1038/s41386-019-0569-3" + }, + { + "author": "Kenneth J Broadley", + "title": "The vascular effects of trace amines and amphetamines ", + "url": "https://doi.org/10.1016/j.pharmthera.2009.11.005" + }, + { + "author": "James R. Docherty, Hadeel A. Alsufyani", + "title": "Cardiovascular and temperature adverse actions of stimulants", + "url": "https://doi.org/10.1111/bph.15465" + }, + { + "author": "James R. Docherty DSc, Hadeel A. Alsufyani MB, PhD", + "title": "Pharmacology of Drugs Used as Stimulants", + "url": "https://doi.org/10.1002/jcph.1918" + }, + { + "author": "Breier Y, Azrak E, Banks W, Kushmakov R, Aleshinskaya I", + "title": "Management of New Onset Amphetamine-Induced Acute Decompensated Heart Failure in a Young Adult: Case Report", + "url": "https://doi.org/10.7759%2Fcureus.43854" + } + ], + "status": "Caution" + }, + "mdma": { + "note": "Risk of serotonin syndrome as both drugs raise serotonin levels. Stimulants also increase the neurotoxic effects of MDMA, in addition to concerns of high blood pressure and unnecessary strain on the heart. As well as potentially causing anxiety and greater physical discomfort due to the combination.", + "sources": [ + { + "author": "J Kehr, F Ichinose, S Yoshitake, M Goiny, T Sievertsson, F Nyberg, T Yoshitake", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Gregory C. Hadlock, Katy M. Webb, Lisa M. McFadden, Pei Wen Chu, Jonathan D. Ellis, Scott C. Allen, David M. Andrenyak, Paula L. Vieira-Brock, Christopher L. German, Kevin M. Conrad, Amanda J. Hoonakker, James W. Gibb, Diana G. Wilkins, Glen R. Hanson and Annette E. Fleckenstein", + "title": "4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse", + "url": "https://doi.org/10.1124/jpet.111.184119 " + }, + { + "author": "Gough B, Ali SF, Slikker W Jr, Holson RR. ", + "title": "Acute effects of 3,4-methylenedioxymethamphetamine (MDMA) on monoamines in rat caudate. (1991)", + "url": "https://doi.org/10.1016/0091-3057(91)90137-q" + }, + { + "author": "Schmidt CJ, Levin JA, Lovenberg W. ", + "title": "In vitro and in vivo neurochemical effects of methylenedioxymethamphetamine on striatal monoaminergic systems in the rat brain. (1987)", + "url": "https://doi.org/10.1016/0006-2952(87)90729-5" + }, + { + "author": "Bankson MG, Cunningham KA.", + "title": "3,4-Methylenedioxymethamphetamine (MDMA) as a unique model of serotonin receptor function and serotonin-dopamine interactions. (2001)", + "url": "https://pubmed.ncbi.nlm.nih.gov/11356903/" + }, + { + "author": "A.C. Parrott", + "title": "Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity (2002)", + "url": "https://doi.org/10.1016/S0091-3057(01)00711-0" + }, + { + "author": "Lisa H. Gold & George F. Koob ", + "title": "MDMA produces stimulant-like conditioned locomotor activity. (1989)", + "url": "https://doi.org/10.1007/BF00445556" + }, + { + "author": "Meng H, Cao J, Kang J, Ying X, Ji J, Reynolds W, Rampe D.", + "title": "Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat ", + "url": "https://doi.org/10.1016/j.toxlet.2011.10.010" + } + ], + "status": "Dangerous" + }, + "mushrooms": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "sources": [ + { + "author": "Goel, D. B., & Zilate, S. (2022)", + "title": "Potential Therapeutic Effects of Psilocybin: A Systematic Review. Cureus, 14(10), e30214.", + "url": "https://doi.org/10.7759/cureus.30214" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T. (2011)", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats: Mephedrone increases both DA and 5-HT in rat brain. British Journal of Pharmacology, 164(8), 1949–1958.", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Papaseit, E., Moltó, J., Muga, R., Torrens, M., De La Torre, R., & Farré, M. (2016)", + "title": "Clinical Pharmacology of the Synthetic Cathinone Mephedrone. In Neuropharmacology of New Psychoactive Substances (NPS) (Vol. 32, pp. 313–331).", + "url": "https://doi.org/10.1007/7854_2016_61" + }, + { + "author": "Passie, T., Seifert, J., Schneider, U., & Emrich, H. M. (2002)", + "title": "The pharmacology of psilocybin. Addiction Biology, 7(4), 357–364.", + "url": "https://doi.org/10.1080/1355621021000005937" + }, + { + "author": "Wood, D. M., Davies, S., Greene, S. L., Button, J., Holt, D. W., Ramsey, J., & Dargan, P. I. (2010)", + "title": "Case series of individuals with analytically confirmed acute mephedrone toxicity. Clinical Toxicology (Philadelphia, Pa.), 48(9), 924–927.", + "url": "https://doi.org/10.3109/15563650.2010.531021" + } + ], + "status": "Low Risk & Synergy" + }, + "opioids": { + "note": "Stimulants increase respiration rate allowing a higher dose of opiates. If the stimulant wears off first then the opiate may overcome the patient and cause respiratory arrest.", + "sources": [ + { + "author": "Cohen, B., Ruth, L. J., & Preuss, C. V. (2025)", + "title": "Opioid Analgesics. In StatPearls.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK459161/" + }, + { + "author": "Dargan, P. I., Sedefov, R., Gallegos, A., & Wood, D. M. (2011)", + "title": "The pharmacology and toxicology of the synthetic cathinone mephedrone (4‐methylmethcathinone). Drug Testing and Analysis, 3(7–8), 454–463.", + "url": "https://doi.org/10.1002/dta.312" + }, + { + "author": "Hadlock, G. C., Webb, K. M., McFadden, L. M., Chu, P. W., Ellis, J. D., Allen, S. C., Andrenyak, D. M., Vieira-Brock, P. L., German, C. L., Conrad, K. M., Hoonakker, A. J., Gibb, J. W., Wilkins, D. G., Hanson, G. R., & Fleckenstein, A. E. (2011)", + "title": "4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse. The Journal of Pharmacology and Experimental Therapeutics, 339(2), 530–536.", + "url": "https://doi.org/10.1124/jpet.111.184119" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T. (2011)", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats: Mephedrone increases both DA and 5-HT in rat brain. British Journal of Pharmacology, 164(8), 1949–1958.", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Meng, H., Cao, J., Kang, J., Ying, X., Ji, J., Reynolds, W., & Rampe, D. (2012)", + "title": "Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat. Toxicology Letters, 208(1), 62–68.", + "url": "https://doi.org/10.1016/j.toxlet.2011.10.010" + }, + { + "author": "Pathan, H., & Williams, J. (2012)", + "title": "Basic opioid pharmacology: an update. British Journal of Pain, 6(1), 11–16.", + "url": "https://doi.org/10.1177/2049463712438493" + } + ], + "status": "Caution" + }, + "pregabalin": { + "note": "There is a significant risk of seizures from this combination. Mephedrone increases respiration rate allowing for a higher dose of sedatives than normal. If mephedrone wears off first, recreational dosages of pregabalin may overcome the individual and cause respiratory arrest. Both substances at recreational dosages cause strain of the heart and may lead to further dangerous heart complications.", + "sources": [ + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben‐Menachem, E. (2004)", + "title": "Pregabalin Pharmacology and Its Relevance to Clinical Practice. Epilepsia, 45(s6), 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Dargan, P. I., Sedefov, R., Gallegos, A., & Wood, D. M. (2011)", + "title": "The pharmacology and toxicology of the synthetic cathinone mephedrone (4‐methylmethcathinone). Drug Testing and Analysis, 3(7–8), 454–463.", + "url": "https://doi.org/10.1002/dta.312" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures: A historical-controlled trial. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N., & Livingston, J. (2006)", + "title": "Aggravation of epilepsy by anti‐epileptic drugs. Developmental Medicine & Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Altair. (n.d)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T. (2011)", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats: Mephedrone increases both DA and 5-HT in rat brain. British Journal of Pharmacology, 164(8), 1949–1958.", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Meng, H., Cao, J., Kang, J., Ying, X., Ji, J., Reynolds, W., & Rampe, D. (2012)", + "title": "Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat. Toxicology Letters, 208(1), 62–68.", + "url": "https://doi.org/10.1016/j.toxlet.2011.10.010" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + } + ], + "status": "Unsafe" + }, + "tramadol": { + "note": "There is a high risk of serotonin syndrome and seizures at recreational dosages. Both substances affect the heart and may lead to further dangerous heart complications at higher dosages. Both can dull each other's effects, so if one wears off before the other it's possible to overdose due to the lack of counteraction. The combination may increase each other's side effects, such as dizziness and drowsiness. At higher dosages, the combination may increase each other’s side effects, such as delirium, mania, and psychosis.", + "sources": [ + { + "author": "Boostani, R., & Derakhshan, S.", + "title": "Tramadol induced seizure: A 3-year study. Caspian Journal of Internal Medicine, 3(3), 484–487 (2012)", + "url": "N/A" + }, + { + "author": "Ener, R. A., Meglathery, S. B., Decker, W. A. V., & Gallagher, R. M.", + "title": "Serotonin Syndrome and Other Serotonergic Disorders: Table 1. Pain Medicine, 4(1), 63–74 (2003)", + "url": "https://doi.org/10.1046/j.1526-4637.2003.03005.x" + }, + { + "author": "Hadlock, G. C., Webb, K. M., McFadden, L. M., Chu, P. W., Ellis, J. D., Allen, S. C., Andrenyak, D. M., Vieira-Brock, P. L., German, C. L., Conrad, K. M., Hoonakker, A. J., Gibb, J. W., Wilkins, D. G., Hanson, G. R., & Fleckenstein, A. E.", + "title": "4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse. The Journal of Pharmacology and Experimental Therapeutics, 339(2), 530–536 (2011)", + "url": "https://doi.org/10.1124/jpet.111.184119" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T.", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats: Mephedrone increases both DA and 5-HT in rat brain. British Journal of Pharmacology, 164(8), 1949–1958 (2011)", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Lagard, C., Vodovar, D., Chevillard, L., Callebert, J., Caillé, F., Pottier, G., Liang, H., Risède, P., Tournier, N., & Mégarbane, B.", + "title": "Investigation of the Mechanisms of Tramadol-Induced Seizures in Overdose in the Rat. Pharmaceuticals, 15(10), 1254 (2022)", + "url": "https://doi.org/10.3390/ph15101254" + }, + { + "author": "Meng, H., Cao, J., Kang, J., Ying, X., Ji, J., Reynolds, W., & Rampe, D.", + "title": "Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat. Toxicology Letters, 208(1), 62–68 (2012)", + "url": "https://doi.org/10.1016/j.toxlet.2011.10.010" + }, + { + "author": "Sansone, R. A., & Sansone, L. A.", + "title": "Tramadol: seizures, serotonin syndrome, and coadministered antidepressants. Psychiatry (Edgmont (Pa.: Township)), 6(4), 17–21 (2009)", + "url": "N/A" + } + ], + "status": "Dangerous" + } + }, + "mescaline": { + "2c-t-x": { + "status": "Caution" + }, + "2c-x": { + "status": "Caution" + }, + "5-meo-xxt": { + "note": "The 5-MeO class of tryptamines can be unpredictable in their interactions", + "status": "Caution" + }, + "alcohol": { + "status": "Low Risk & Decrease" + }, + "amphetamines": { + "note": "The focus and anxiety caused by stimulants is magnified by psychedelics and results in an increased risk of thought loops", + "status": "Caution" + }, + "amt": { + "status": "Dangerous" + }, + "benzodiazepines": { + "status": "Low Risk & Decrease" + }, + "caffeine": { + "note": "High doses of caffeine are uncomfortable and this will be magnified by psychedelics", + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "cocaine": { + "note": "The focus and anxiety caused by stimulants is magnified by psychedelics and results in an increased risk of thought loops", + "status": "Caution" + }, + "dextromethorphan": { + "status": "Low Risk & Synergy" + }, + "diphenhydramine": { + "note": "At 25-50mg, DPH may assist with side effects of the mescaline such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and mescaline is cautioned against. Mescaline is likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma.", + "sources": [ + { + "author": "Dinis-Oliveira, R. J., Pereira, C. L., & Dias da Silva, D. (2019)", + "title": "Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions. Current Molecular Pharmacology, 12(3), 184–194.", + "url": "https://doi.org/10.2174/1874467211666181010154139" + }, + { + "author": "ScienceDirect Topics. (n.d.)", + "title": "Mescaline - an overview.", + "url": "https://www.sciencedirect.com/topics/neuroscience/mescaline" + }, + { + "author": "Schaefer, T. S., Patel, P., & Zito, P. M. (2025)", + "title": "Antiemetic Histamine H1 Receptor Blockers. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK533003/" + }, + { + "author": "Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)", + "title": "Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.", + "url": "https://doi.org/10.3389/fpsyt.2021.657397" + }, + { + "author": "Vamvakopoulou, I. A., Narine, K. A. D., Campbell, I., Dyck, J. R. B., & Nutt, D. J. (2023)", + "title": "Mescaline: The forgotten psychedelic. Neuropharmacology, 222, 109294.", + "url": "https://doi.org/10.1016/j.neuropharm.2022.109294" + }, + { + "author": "Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)", + "title": "Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.", + "url": "https://doi.org/10.1016/j.jaip.2022.07.018" + } + ], + "status": "Caution" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "dox": { + "status": "Caution" + }, + "ghb/gbl": { + "status": "Low Risk & Decrease" + }, + "ketamine": { + "status": "Low Risk & Synergy" + }, + "lithium": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + } + ], + "status": "Dangerous" + }, + "lsd": { + "status": "Low Risk & Synergy" + }, + "maois": { + "status": "Caution" + }, + "mdma": { + "status": "Low Risk & Synergy" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "status": "Low Risk & Synergy" + }, + "nbomes": { + "status": "Caution" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "status": "Low Risk & No Synergy" + }, + "pcp": { + "status": "Low Risk & Synergy" + }, + "pregabalin": { + "note": "Caution should be given due to mescaline’s stimulating effects and pregabalin’s seizure concerns at higher dosages. Pregabalin may reduce the vasoconstriction, anxiety, and other side effects of mescaline. Additionally, Pregabalin may increase mescaline’s inhibition and risk of injury.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "Freidel, N., Kreuder, L., Rabinovitch, B. S., Chen, F. Y., Huang, R. S. T., & Lewis, E. C. (2024)", + "title": "Psychedelics, epilepsy, and seizures: a review. Frontiers in Pharmacology, 14.", + "url": "https://doi.org/10.3389/fphar.2023.1326815" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures: A historical-controlled trial. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Simonsson, O., Goldberg, S. B., Chambers, R., Osika, W., Long, D. M., & Hendricks, P. S. (2022)", + "title": "Prevalence and associations of classic psychedelic-related seizures in a population-based sample. Drug and Alcohol Dependence, 239, 109586.", + "url": "https://doi.org/10.1016/j.drugalcdep.2022.109586" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Soto-Angona, Ó., Fortea, A., Fortea, L., Martínez-Ramírez, M., Santamarina, E., López, F. J. G., Knudsen, G. M., & Ona, G. (2024)", + "title": "Do classic psychedelics increase the risk of seizures? A scoping review. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 85, 35–42.", + "url": "https://doi.org/10.1016/j.euroneuro.2024.05.002" + } + ], + "status": "Caution" + }, + "ssris": { + "status": "Low Risk & Decrease" + }, + "tramadol": { + "note": "This combination can cause seizures due to the lowering of the threshold by tramadol and the potential of mescaline to cause seziures.", + "status": "Unsafe" + } + }, + "mushrooms": { + "2c-t-x": { + "status": "Low Risk & Synergy" + }, + "2c-x": { + "status": "Low Risk & Synergy" + }, + "5-meo-xxt": { + "status": "Low Risk & Synergy" + }, + "alcohol": { + "status": "Low Risk & Decrease" + }, + "amphetamines": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "amt": { + "status": "Low Risk & Synergy" + }, + "benzodiazepines": { + "status": "Low Risk & Decrease" + }, + "caffeine": { + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "cocaine": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "status": "Caution" + }, + "dextromethorphan": { + "status": "Low Risk & Synergy" + }, + "diphenhydramine": { + "note": "At 25-50mg, DPH may assist with side effects of the psilocybin such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and psilocybin is cautioned against. Psilocybin is likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma.", + "sources": [ + { + "author": "Goel, D. B., & Zilate, S. (2022)", + "title": "Potential Therapeutic Effects of Psilocybin: A Systematic Review. Cureus, 14(10), e30214.", + "url": "https://doi.org/10.7759/cureus.30214" + }, + { + "author": "Passie, T., Seifert, J., Schneider, U., & Emrich, H. M. (2002)", + "title": "The pharmacology of psilocybin. Addiction Biology, 7(4), 357–364.", + "url": "https://doi.org/10.1080/1355621021000005937" + }, + { + "author": "Schaefer, T. S., Patel, P., & Zito, P. M. (2025)", + "title": "Antiemetic Histamine H1 Receptor Blockers. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK533003/" + }, + { + "author": "Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)", + "title": "Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12.", + "url": "https://doi.org/10.3389/fpsyt.2021.657397" + }, + { + "author": "Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)", + "title": "Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.", + "url": "https://doi.org/10.1016/j.jaip.2022.07.018" + }, + { + "author": "Yerubandi, A., Thomas, J. E., Bhuiya, N. M. M. A., Harrington, C., Villa Zapata, L., & Caballero, J. (2024)", + "title": "Acute Adverse Effects of Therapeutic Doses of Psilocybin. JAMA Network Open, 7(4), e245960.", + "url": "https://doi.org/10.1001/jamanetworkopen.2024.5960" + } + ], + "status": "Caution" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "dox": { + "status": "Low Risk & Synergy" + }, + "ghb/gbl": { + "status": "Low Risk & Decrease" + }, + "ketamine": { + "status": "Low Risk & Synergy" + }, + "lithium": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + } + ], + "status": "Dangerous" + }, + "lsd": { + "status": "Low Risk & Synergy" + }, + "maois": { + "status": "Low Risk & Synergy" + }, + "mdma": { + "status": "Low Risk & Synergy" + }, + "mephedrone": { + "note": "Stimulants increase anxiety levels and the risk of thought loops which can lead to negative experiences", + "sources": [ + { + "author": "Goel, D. B., & Zilate, S. (2022)", + "title": "Potential Therapeutic Effects of Psilocybin: A Systematic Review. Cureus, 14(10), e30214.", + "url": "https://doi.org/10.7759/cureus.30214" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T. (2011)", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats: Mephedrone increases both DA and 5-HT in rat brain. British Journal of Pharmacology, 164(8), 1949–1958.", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Papaseit, E., Moltó, J., Muga, R., Torrens, M., De La Torre, R., & Farré, M. (2016)", + "title": "Clinical Pharmacology of the Synthetic Cathinone Mephedrone. In Neuropharmacology of New Psychoactive Substances (NPS) (Vol. 32, pp. 313–331).", + "url": "https://doi.org/10.1007/7854_2016_61" + }, + { + "author": "Passie, T., Seifert, J., Schneider, U., & Emrich, H. M. (2002)", + "title": "The pharmacology of psilocybin. Addiction Biology, 7(4), 357–364.", + "url": "https://doi.org/10.1080/1355621021000005937" + }, + { + "author": "Wood, D. M., Davies, S., Greene, S. L., Button, J., Holt, D. W., Ramsey, J., & Dargan, P. I. (2010)", + "title": "Case series of individuals with analytically confirmed acute mephedrone toxicity. Clinical Toxicology (Philadelphia, Pa.), 48(9), 924–927.", + "url": "https://doi.org/10.3109/15563650.2010.531021" + } + ], + "status": "Low Risk & Synergy" + }, + "mescaline": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "status": "Low Risk & Synergy" + }, + "nbomes": { + "status": "Low Risk & Synergy" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "status": "Low Risk & No Synergy" + }, + "pcp": { + "status": "Low Risk & Synergy" + }, + "pregabalin": { + "note": "Pregabalin may reduce the anxiety and other possible side effects of Psilocybin Mushrooms. Additionally, the combination may increase inhibition, dizziness, and risk of injury.", + "sources": [ + { + "author": "Cross, A. L., Viswanath, O., & Sherman, A. L. (2025)", + "title": "Pregabalin. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK470341/" + }, + { + "author": "ScienceDirect Topics. (n.d.)", + "title": "Psilocybin - an overview", + "url": "https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/psilocybin" + } + ], + "status": "Low Risk & Synergy" + }, + "ssris": { + "status": "Low Risk & Decrease" + }, + "tramadol": { + "note": "Tramadol is well known to lower seizure threshold and psychedelics also cause occasional seizures.", + "status": "Unsafe" + } + }, + "mxe": { + "2c-t-x": { + "status": "Caution" + }, + "2c-x": { + "status": "Low Risk & Synergy" + }, + "5-meo-xxt": { + "note": "Little information exists about this combination.", + "status": "Low Risk & Synergy" + }, + "alcohol": { + "note": "There is a high risk of memory loss, vomiting and severe ataxia from this combination.", + "status": "Dangerous" + }, + "amphetamines": { + "note": "Risk of tachycardia, hypertension, and manic states", + "status": "Caution" + }, + "amt": { + "status": "Dangerous" + }, + "benzodiazepines": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place the affected individual in the recovery position to prevent vomit aspiration from excess.", + "status": "Caution" + }, + "caffeine": { + "note": "No likely interactions", + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "status": "Low Risk & Synergy" + }, + "cocaine": { + "note": "Stimulants taken with MXE can lead to hypermanic states much more easily, especially if sleep is avoided.", + "status": "Caution" + }, + "dextromethorphan": { + "note": "There is a risk of serotonin syndrome when combining DXM with MXE, due to DXM and MXE both being SRI’s. MXE and DXM having notable affinities for the serotonin transporter.", + "sources": [ + { + "author": "Bryan L. Roth, Simon Gibbons, Warunya Arunotayanun, Xi-Ping Huang, Vincent Setola, Ric Treble, Les Iversen", + "title": "The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor", + "url": "https://doi.org/10.1371/journal.pone.0059334" + }, + { + "author": "Matteo Marti, Giuseppe Talani, Cristina Miliano, Sabrine Bilel, Francesca Biggio, Jessica Bratzu, Marco Diana, Maria Antonietta De Luca, Liana Fattore", + "title": "New insights into methoxetamine mechanisms of action: Focus on serotonergic 5-HT2 receptors in pharmacological and behavioral effects in the rat ", + "url": "https://doi.org/10.1016/j.expneurol.2021.113836" + }, + { + "author": "Laura Hondebrink, Emma E.J. Kasteel, Anke M. Tukker, Fiona M.J. Wijnolts, Anouk H.A. Verboven, Remco H.S. Westerink", + "title": "Neuropharmacological characterization of the new psychoactive substance methoxetamine", + "url": "https://doi.org/10.1016/j.neuropharm.2017.04.035" + }, + { + "author": "Linda L. Werling, Ashleigh Keller, Julie G. Frank, Samer J. Nuwayhid", + "title": "A comparison of the binding profiles of dextromethorphan, memantine, fluoxetine and amitriptyline: Treatment of involuntary emotional expression disorder", + "url": "https://doi.org/10.1016/j.expneurol.2007.06.013" + }, + { + "author": "Linda Nguyen, Kelan L. Thomas, Brandon P. Lucke-Wold, John Z. Cavendish, Molly S. Crowe, Rae R. Matsumoto", + "title": "Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders", + "url": "https://doi.org/10.1016/j.pharmthera.2016.01.016" + } + ], + "status": "Unsafe" + }, + "diphenhydramine": { + "note": "There is a high risk of serotonin syndrome from this combination. Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. MXE has a high likelihood of increasing DPH's deliriant effects at higher dosages and can greatly increase the risk of injury, mania, and psychosis. Medical dosages are unlikely to be of concern.", + "sources": [ + { + "author": "Clark, J. H., Meltzer, E. O., & Naclerio, R. M. (2025)", + "title": "Diphenhydramine: It is time to say a final goodbye. World Allergy Organization Journal, 18(2), 101027.", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Ener, R. A., Meglathery, S. B., Decker, W. A. V., & Gallagher, R. M. (2003)", + "title": "Serotonin Syndrome and Other Serotonergic Disorders: Table 1. Pain Medicine, 4(1), 63–74.", + "url": "https://doi.org/10.1046/j.1526-4637.2003.03005.x" + }, + { + "author": "Marti, M., Talani, G., Miliano, C., Bilel, S., Biggio, F., Bratzu, J., Diana, M., De Luca, M. A., & Fattore, L. (2021)", + "title": "New insights into methoxetamine mechanisms of action: Focus on serotonergic 5-HT2 receptors in pharmacological and behavioral effects in the rat. Experimental Neurology, 345, 113836.", + "url": "https://doi.org/10.1016/j.expneurol.2021.113836" + }, + { + "author": "Roth, B. L., Gibbons, S., Arunotayanun, W., Huang, X.-P., Setola, V., Treble, R., & Iversen, L. (2013)", + "title": "The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor. PLoS ONE, 8(3), e59334.", + "url": "https://doi.org/10.1371/journal.pone.0059334" + }, + { + "author": "Varghese, E., Abate, M. A., Hu, L., Kaplan, J., Kraner, J., Long, D. L., Sorg, M., Mock, A., Greenwald, M., & Andrew, T. (2015)", + "title": "Characterization of Diphenhydramine-Related Accidental Overdose Deaths. Academic Forensic Pathology, 5(1), 105–115.", + "url": "https://doi.org/10.23907/2015.011" + } + ], + "status": "Dangerous" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "dox": { + "note": "As an NMDA antagonist MXE potentiates DOx which can be unpleasantly intense", + "status": "Caution" + }, + "ghb/gbl": { + "note": "Both substances cause ataxia and bring a risk of vomiting and unconsciousness. If the individual falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.", + "status": "Dangerous" + }, + "ketamine": { + "status": "Low Risk & Synergy" + }, + "lithium": { + "note": "There is a risk of serotonin syndrome when combining Lithium with MXE, as Lithium can induce serotonin syndrome in conjunction with other serotonergic drugs, and MXE has shown a notable affinity for the serotonin transporter.", + "sources": [ + { + "author": "Lenox, R. H., & Hahn, C. G.", + "title": "Overview of the mechanism of action of lithium in the brain: fifty-year update (2000)", + "url": "https://pubmed.ncbi.nlm.nih.gov/10826655/" + }, + { + "author": "Shahani, L.", + "title": "Venlafaxine Augmentation With Lithium Leading to Serotonin Syndrome (2012)", + "url": "https://doi.org/10.1176/appi.neuropsych.11080196" + }, + { + "author": "DeBattista, C., Sofuoglu, M., & Schatzberg, A. F.", + "title": "Serotonergic synergism: the risks and benefits of combining the selective serotonin reuptake inhibitors with other serotonergic drugs (1998)", + "url": "https://doi.org/10.1016/S0006-3223(98)00161-9" + }, + { + "author": "Massot, O.", + "title": "5-HT1B Receptors: A Novel Target for Lithium: Possible Involvement in Mood Disorders (1999)", + "url": "https://doi.org/10.1016/S0893-133X(99)00042-1" + }, + { + "author": "Roth, B. L., Gibbons, S., Arunotayanun, W., Huang, X.-P., Setola, V., Treble, R., & Iversen, L.", + "title": "The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor (2013)", + "url": "https://doi.org/10.1371/journal.pone.0059334" + }, + { + "author": "Marti, M., Talani, G., Miliano, C., Bilel, S., Biggio, F., Bratzu, J., Diana, M., De Luca, M. A., & Fattore, L.", + "title": "New insights into methoxetamine mechanisms of action: Focus on serotonergic 5-HT2 receptors in pharmacological and behavioral effects in the rat (2021)", + "url": "https://doi.org/10.1016/j.expneurol.2021.113836" + } + ], + "status": "Dangerous" + }, + "lsd": { + "status": "Low Risk & Synergy" + }, + "maois": { + "note": "MAO-B inhibitors appear to increase the potency of MXE. MAO-A inhbitors have some negative reports associated with the combination but there isn't much information available", + "status": "Unsafe" + }, + "mdma": { + "note": "There have been reports of risky serotonergic interactions when the two are taken at the same time, but MXE taken to the end of an MDMA experience does not appear to cause the same issues.", + "status": "Caution" + }, + "mescaline": { + "status": "Low Risk & Synergy" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "nbomes": { + "note": "As an NMDA antagonist MXE potentiates NBOMes which can be unpleasantly intense", + "status": "Caution" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "note": "This combination can potentiate the effects of the opioid", + "status": "Dangerous" + }, + "pcp": { + "note": "There are no reports available about this combination", + "status": "Caution" + }, + "pregabalin": { + "note": "Pregabalin and MXE may synergize and increase each other’s negative side effects such as nausea, dizziness, and loss of consciousness. Caution is advised for anything above low dosages due to seizure concerns, and all dosages for individuals with higher risk seizure profiles and or behavior.", + "sources": [ + { + "author": "Anwar, S., Cooper, J., Rahman, J., Sharma, C., & Langford, R. (2019)", + "title": "Prolonged Perioperative Use of Pregabalin and Ketamine to Prevent Persistent Pain after Cardiac Surgery. Anesthesiology, 131(1), 119–131.", + "url": "https://doi.org/10.1097/ALN.0000000000002751" + }, + { + "author": "Arendt-Nielsen, L., Mansikka, H., Staahl, C., Rees, H., Tan, K., Smart, T. S., Monhemius, R., Suzuki, R., & Drewes, A. M. (2011)", + "title": "A Translational Study of the Effects of Ketamine and Pregabalin on Temporal Summation of Experimental Pain: Regional Anesthesia and Pain Medicine, 36(6), 585–591.", + "url": "https://doi.org/10.1097/AAP.0b013e31822b0db0" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben‐Menachem, E. (2004)", + "title": "Pregabalin Pharmacology and Its Relevance to Clinical Practice. Epilepsia, 45(s6), 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures: A historical-controlled trial. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N., & Livingston, J. (2006)", + "title": "Aggravation of epilepsy by anti‐epileptic drugs. Developmental Medicine & Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–552.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Marti, M., Talani, G., Miliano, C., Bilel, S., Biggio, F., Bratzu, J., Diana, M., De Luca, M. A., & Fattore, L. (2021)", + "title": "New insights into methoxetamine mechanisms of action: Focus on serotonergic 5-HT2 receptors in pharmacological and behavioral effects in the rat. Experimental Neurology, 345, 113836.", + "url": "https://doi.org/10.1016/j.expneurol.2021.113836" + }, + { + "author": "Martinez, V., Cymerman, A., Ben Ammar, S., Fiaud, J. F., Rapon, C., Poindessous, F., Judet, T., Chauvin, M., Bouhassira, D., Sessler, D., Mazoit, X., & Fletcher, D. (2014)", + "title": "The analgesic efficiency of combined pregabalin and ketamine for total hip arthroplasty: a randomised, double‐blind, controlled study. Anaesthesia, 69(1), 46–52.", + "url": "https://doi.org/10.1111/anae.12495" + }, + { + "author": "Roth, B. L., Gibbons, S., Arunotayanun, W., Huang, X.-P., Setola, V., Treble, R., & Iversen, L. (2013)", + "title": "The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor. PLoS ONE, 8(3), e59334.", + "url": "https://doi.org/10.1371/journal.pone.0059334" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Zhou, Y., Sun, W., Fu, Y., Wang, J., Fan, J., Liang, Y., Jia, W., & Han, R. (2024)", + "title": "Effect of esketamine combined with pregabalin on acute postsurgical pain in patients who underwent resection of spinal neoplasms: a randomized controlled trial. Pain, 165(9), e96–e105.", + "url": "https://doi.org/10.1097/j.pain.0000000000003211" + } + ], + "status": "Caution" + }, + "ssris": { + "note": "Depending on the SSRI this combination can be unpredictable", + "status": "Caution" + }, + "tramadol": { + "status": "Dangerous" + } + }, + "nbomes": { + "2c-t-x": { + "status": "Caution" + }, + "2c-x": { + "status": "Caution" + }, + "5-meo-xxt": { + "note": "The 5-MeO class of tryptamines can be unpredictable in their interactions and the NBOMes are known to be unpredictable even alone. This combination is best avoided", + "status": "Caution" + }, + "alcohol": { + "status": "Low Risk & Decrease" + }, + "amphetamines": { + "note": "Amphetamines and NBOMes both provide considerable stimulation. When combined they can result in tachycardia, hypertension, vasoconstriction and in extreme cases heart failure. The anxiogenic and focusing effects of stimulants are also not good in combination with psychedelics as they can lead to unpleasant thought loops. NBOMes are known to cause seizures and stimulants can increase this risk.", + "status": "Unsafe" + }, + "amt": { + "status": "Dangerous" + }, + "benzodiazepines": { + "status": "Low Risk & Decrease" + }, + "caffeine": { + "note": "Caffeine can bring out the natural stimulation from psychedelic drugs to make it uncomfortable. High doses can cause anxiety which is hard to handle while tripping", + "status": "Caution" + }, + "cannabis": { + "note": "Cannabis has an unexpectedly strong and somewhat unpredictable synergy with psychedelics.", + "status": "Caution" + }, + "cocaine": { + "note": "Cocaine and NBOMes both provide considerable stimulation. When combined they can result in severe vasoconstriction, tachycardia, hypertension, and in extreme cases heart failure.", + "status": "Unsafe" + }, + "dextromethorphan": { + "status": "Unsafe" + }, + "diphenhydramine": { + "note": "At 25-50mg, DPH may assist with side effects of the NBOMe drugs such as nausea and anxiety. At higher dosages, the combination of a deliriant (DPH) and NBOMe drugs is cautioned against. NBOMes are likely to increase the deliriant and negative effects of DPH, in addition to increasing the risk of severe injury and mental trauma. NBOMes and DPH at recreational dosages have additional cardiac concerns such as vasoconstriction, tachycardia, hypertension, which in combination may be exacerbated.", + "sources": [ + { + "author": "Kyriakou, C., Marinelli, E., Frati, P., Santurro, A., Afxentiou, M., Zaami, S., & Busardo, F. P. (2015)", + "title": "NBOMe: new potent hallucinogens--pharmacology, analytical methods, toxicities, fatalities: a review. European Review for Medical and Pharmacological Sciences, 19(17), 3270–3281.", + "url": "https://pubmed.ncbi.nlm.nih.gov/26400534/" + }, + { + "author": "Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)", + "title": "Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.", + "url": "https://doi.org/10.3389/fpsyt.2021.657397" + }, + { + "author": "Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)", + "title": "Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.", + "url": "https://doi.org/10.1016/j.jaip.2022.07.018" + }, + { + "author": "Zawilska, J. B., Kacela, M., & Adamowicz, P. (2020)", + "title": "NBOMes–Highly Potent and Toxic Alternatives of LSD. Frontiers in Neuroscience, 14, 78.", + "url": "https://doi.org/10.3389/fnins.2020.00078" + } + ], + "status": "Caution" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "dox": { + "status": "Caution" + }, + "ghb/gbl": { + "status": "Low Risk & Decrease" + }, + "ketamine": { + "status": "Low Risk & Synergy" + }, + "lithium": { + "note": "There are a large number of reports indicating a high seizure and psychosis risk from this combination.", + "sources": [ + { + "author": "Sandeep M Nayak, Natalie Gukasyan, Frederick S Barrett , Earth Erowid , Fire Erowid , Roland R Griffiths", + "title": "Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports", + "url": "https://doi.org/10.1055/a-1524-2794" + }, + { + "author": "Erowid", + "title": "Erowid Interactions", + "url": "https://erowid.org/chemicals/lsd/lsd_interactions.shtml" + }, + { + "author": "freshboi88", + "title": "I Was Only on One Dose", + "url": "https://erowid.org/experiences/exp.php?ID=93681" + }, + { + "author": "YouWerentYouAnymore", + "title": "Brought My Worst Thoughts to Life", + "url": "https://erowid.org/experiences/exp.php?ID=110780" + }, + { + "author": "Otto Simonsson, Peper S. Hendricks, Richard Chambers, Walter Osika, Simon B. Goldberg", + "title": "Prevalence and associations of challenging, difficult or distressing experiences using classic psychedelics", + "url": "https://doi.org/10.1016/j.jad.2023.01.073" + }, + { + "author": "Umemura, Y., Andrew, T. A., Jacobs, V. L., Giustini, A. J., Lewis, L. D., & Filiano, J. J.", + "title": "Fatal 251-NBOMe Intoxication: A New Recreational Risk. (2015)", + "url": "https://doi.org/10.23907/2015.009" + } + ], + "status": "Dangerous" + }, + "lsd": { + "sources": [ + { + "author": "Umemura, Y., Andrew, T. A., Jacobs, V. L., Giustini, A. J., Lewis, L. D., & Filiano, J. J.", + "title": "Fatal 251-NBOMe Intoxication: A New Recreational Risk. Academic Forensic Pathology", + "url": "https://doi.org/10.23907/2015.009" + } + ], + "status": "Low Risk & Synergy" + }, + "maois": { + "note": "MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably", + "status": "Caution" + }, + "mdma": { + "status": "Caution" + }, + "mescaline": { + "status": "Caution" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "note": "As an NMDA antagonist MXE potentiates NBOMes which can be unpleasantly intense", + "status": "Caution" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "status": "Low Risk & No Synergy" + }, + "pcp": { + "status": "Low Risk & Synergy" + }, + "pregabalin": { + "note": "NBOMes and pregabalin are reported to have significant seizure concerns that are likely to increase in combination. Therapeutic dosages of pregabalin are unlikely to be of concern and may decrease NBOMes side effects such as vasoconstriction and anxiety.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Kyriakou, C., Marinelli, E., Frati, P., Santurro, A., Afxentiou, M., Zaami, S., & Busardo, F. P. (2015)", + "title": "NBOMe: new potent hallucinogens--pharmacology, analytical methods, toxicities, fatalities: a review. European Review for Medical and Pharmacological Sciences, 19(17), 3270–3281.", + "url": "https://pubmed.ncbi.nlm.nih.gov/26400534/" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Zawilska, J. B., Kacela, M., & Adamowicz, P. (2020)", + "title": "NBOMes–Highly Potent and Toxic Alternatives of LSD. Frontiers in Neuroscience, 14, 78.", + "url": "https://doi.org/10.3389/fnins.2020.00078" + } + ], + "status": "Dangerous" + }, + "ssris": { + "status": "Low Risk & Decrease" + }, + "tramadol": { + "note": "Tramadol is well known to lower seizure threshold and NBOMes have also shown a tendency to cause severe seizures", + "status": "Unsafe" + } + }, + "nitrous": { + "2c-t-x": { + "status": "Low Risk & Synergy" + }, + "2c-x": { + "status": "Low Risk & Synergy" + }, + "5-meo-xxt": { + "status": "Low Risk & Synergy" + }, + "alcohol": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are likely.", + "status": "Caution" + }, + "amphetamines": { + "status": "Low Risk & Synergy" + }, + "amt": { + "status": "Low Risk & Synergy" + }, + "benzodiazepines": { + "status": "Low Risk & Decrease" + }, + "caffeine": { + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "status": "Low Risk & Synergy" + }, + "cocaine": { + "status": "Low Risk & Synergy" + }, + "dextromethorphan": { + "status": "Low Risk & Synergy" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "dox": { + "status": "Low Risk & Synergy" + }, + "ghb/gbl": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are likely.", + "status": "Caution" + }, + "ketamine": { + "status": "Low Risk & Synergy" + }, + "lithium": { + "note": "We are unable to find a report of concerns for CNS depression caused by Lithium.", + "sources": [ + { + "author": "Drugbank", + "title": "Lithium Carbonate", + "url": "https://go.drugbank.com/drugs/DB14509" + } + ], + "status": "Low Risk & No Synergy" + }, + "lsd": { + "status": "Low Risk & Synergy" + }, + "maois": { + "status": "Low Risk & No Synergy" + }, + "mdma": { + "status": "Low Risk & Synergy" + }, + "mescaline": { + "status": "Low Risk & Synergy" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "status": "Low Risk & Synergy" + }, + "nbomes": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are likely.", + "status": "Caution" + }, + "pcp": { + "status": "Low Risk & Synergy" + }, + "pregabalin": { + "note": "Both substances potentiate the ataxia and sedation caused by the other, and may increase the risk of loss of consciousness at higher dosages. While unconscious, vomit aspiration is a risk if not placed in the recovery position. The combination may increase inhibition and risk of injury. Additionally, abuse of nitrous while under the influence of pregabalin may increase the risk of seizures. Medical dosages are unlikely to be a concern.", + "sources": [ + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben‐Menachem, E. (2004)", + "title": "Pregabalin Pharmacology and Its Relevance to Clinical Practice. Epilepsia, 45(s6), 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Cross, A. L., Viswanath, O., & Sherman, A. L. (2025)", + "title": "Pregabalin. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK470341/" + }, + { + "author": "Davidson, L. T. (2023)", + "title": "Recreational use of nitrous oxide causes seizure, pneumothorax, pneumomediastinum, and pneumopericardium: nitrous oxide and its harm, a case report. Upsala Journal of Medical Sciences, 128, 10.48101/ujms.v128.10281.", + "url": "https://doi.org/10.48101/ujms.v128.10281" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures: A historical-controlled trial. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N., & Livingston, J. (2006)", + "title": "Aggravation of epilepsy by anti‐epileptic drugs. Developmental Medicine & Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Knuf, K., & Maani, C. V. (2025)", + "title": "Nitrous Oxide. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK532922/" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Wagner, S., Clark, M., Wesche, D., Doedens, D., & Lloyd, A. (1992)", + "title": "Asphyxial Deaths from the Recreational Use of Nitrous Oxide. Journal of Forensic Sciences, 37(4), 1008–1015.", + "url": "https://doi.org/10.1520/JFS13286J" + } + ], + "status": "Caution" + }, + "ssris": { + "status": "Low Risk & No Synergy" + }, + "tramadol": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are likely.", + "status": "Caution" + } + }, + "opioids": { + "2c-t-x": { + "note": "No expected interactions, some opioids have serotonin action, and could lead to Serotonin Syndrome or a seizure. These are pretty much only to Pentazocine, Methadone, Tramadol, Tapenatdol.", + "status": "Low Risk & No Synergy" + }, + "2c-x": { + "status": "Low Risk & No Synergy" + }, + "5-meo-xxt": { + "status": "Low Risk & No Synergy" + }, + "alcohol": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place the affected individual in the recovery position to prevent vomit aspiration from excess. Memory blackouts are likely", + "status": "Dangerous" + }, + "amphetamines": { + "note": "Stimulants increase respiration rate allowing for a higher dose of opiates than normal. If the stimulant wears off first then the opiate may overcome the individual and cause respiratory arrest.", + "status": "Caution" + }, + "amt": { + "note": "No unexpected interactions", + "status": "Low Risk & No Synergy" + }, + "benzodiazepines": { + "note": "Central nervous system and/or respiratory-depressant effects may be additively or synergistically present. The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position Blackouts/memory loss likely", + "status": "Dangerous" + }, + "caffeine": { + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "status": "Low Risk & Synergy" + }, + "cocaine": { + "note": "Stimulants increase respiration rate allowing for a higher dose of opiates than normal. If the stimulant wears off first then the opiate may overcome the individual and cause respiratory arrest.", + "status": "Dangerous" + }, + "dextromethorphan": { + "note": "CNS depression, difficult breathing, heart issues, hepatoxic, just very unsafe combination all around. Additionally if one takes DXM, their tolerance of opiates goes down slightly, thus causing additional synergistic effects.", + "status": "Dangerous" + }, + "diphenhydramine": { + "note": "Both substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and unconsciousness. The interaction will cause greater inhibition and risk of injury. DPH reduces histamine release by opioids, which reduces the itching side effect from opioids. DPH may reduce the nausea caused by opioids. DPH inhibits CYP2D6 activity which can lead to a reduction of effects in some opioids and potentiation of effects in others.", + "sources": [ + { + "author": "Akutsu, T., Kobayashi, K., Sakurada, K., Ikegaya, H., Furihata, T., & Chiba, K. (2007)", + "title": "Identification of human cytochrome p450 isozymes involved in diphenhydramine N-demethylation. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 35(1), 72–78.", + "url": "https://doi.org/10.1124/dmd.106.012088" + }, + { + "author": "Dinwiddie, A. T., Tanz, L. J., & Bitting, J. (2022)", + "title": "Notes from the Field: Antihistamine Positivity and Involvement in Drug Overdose Deaths — 44 Jurisdictions, United States, 2019–2020. Morbidity and Mortality Weekly Report, 71(41), 1308–1310.", + "url": "https://doi.org/10.15585/mmwr.mm7141a4" + }, + { + "author": "Grönlund, J., Saari, T. I., Hagelberg, N. M., Neuvonen, P. J., Olkkola, K. T., & Laine, K. (2010)", + "title": "Exposure to oral oxycodone is increased by concomitant inhibition of CYP2D6 and 3A4 pathways, but not by inhibition of CYP2D6 alone. British Journal of Clinical Pharmacology, 70(1), 78–87.", + "url": "https://doi.org/10.1111/j.1365-2125.2010.03653.x" + }, + { + "author": "Hamelin, B. (2000)", + "title": "Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity. Clinical Pharmacology & Therapeutics, 67(5), 466–477.", + "url": "https://doi.org/10.1067/mcp.2000.106464" + }, + { + "author": "Heiskanen, T., & Kalso, E. (2012)", + "title": "Non-analgesic effects of opioids: interactions between opioids and other drugs. Current Pharmaceutical Design, 18(37), 6079–6089.", + "url": "https://doi.org/10.2174/138161212803582423" + }, + { + "author": "Nahid, N. A., McDonough, C. W., Wei, Y.-J. J., Cicali, E. J., Gong, Y., Fillingim, R. B., & Johnson, J. A. (2024)", + "title": "Use of CYP2D6 Inhibitors with CYP2D6 Opioids: Association with Emergency Department Visits for Pain. Clinical Pharmacology and Therapeutics, 116(4), 1005–1012.", + "url": "https://doi.org/10.1002/cpt.3314" + }, + { + "author": "Okutani, H., Lo Vecchio, S., & Arendt‐Nielsen, L. (2024)", + "title": "Mechanisms and treatment of opioid‐induced pruritus: Peripheral and central pathways. European Journal of Pain, 28(2), 214–230.", + "url": "https://doi.org/10.1002/ejp.2180" + }, + { + "author": "Sicari, V., Patel, P., & Zabbo, C. P. (2025)", + "title": "Diphenhydramine. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + }, + { + "author": "Swegle, J. M., & Logemann, C. (2006)", + "title": "Management of common opioid-induced adverse effects. American Family Physician, 74(8), 1347–1354.", + "url": "https://pubmed.ncbi.nlm.nih.gov/17087429/" + }, + { + "author": "Wei, Y.-J. J., Winterstein, A. G., Schmidt, S., Fillingim, R. B., Daniels, M. J., DeKosky, S. T., & Schmidt, S. (2025)", + "title": "Association of initiating CYP2D6-metabolized opioids with risks of adverse outcomes in older adults receiving antidepressants: A retrospective cohort study. PLOS Medicine, 22(6), e1004620.", + "url": "https://doi.org/10.1371/journal.pmed.1004620" + }, + { + "author": "Whitt, A., & Jortani, S. (2023)", + "title": "B-337 Case Report: Fatal Opioid Overdose Induced by Over-the-Counter Cold Medication Diphenhydramine. Clinical Chemistry, 69(Supplement_1), hvad097.656.", + "url": "https://doi.org/10.1093/clinchem/hvad097.656" + } + ], + "status": "Unsafe" + }, + "dmt": { + "status": "Low Risk & No Synergy" + }, + "dox": { + "note": "No unexpected interactions.", + "status": "Low Risk & No Synergy" + }, + "ghb/gbl": { + "note": "The two substances potentiate each other strongly and unpredictably, very rapidly leading to unconsciousness. While unconscious, vomit aspiration is a risk if not placed in the recovery position", + "status": "Dangerous" + }, + "ketamine": { + "note": "Both substances bring a risk of vomiting and unconsciousness. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position.", + "status": "Dangerous" + }, + "lsd": { + "status": "Low Risk & No Synergy" + }, + "maois": { + "note": "Coadministration of monoamine oxidase inhibitors (MAOIs) with certain opioids has been associated with rare reports of severe and fatal adverse reactions. There appear to be two types of interaction, an excitatory and a depressive one. Symptoms of the excitatory reaction may include agitation, headache, diaphoresis, hyperpyrexia, flushing, shivering, myoclonus, rigidity, tremor, diarrhea, hypertension, tachycardia, seizures, and coma. Death has occurred in some cases.", + "status": "Caution" + }, + "mdma": { + "status": "Low Risk & No Synergy" + }, + "mephedrone": { + "note": "Stimulants increase respiration rate allowing a higher dose of opiates. If the stimulant wears off first then the opiate may overcome the patient and cause respiratory arrest.", + "sources": [ + { + "author": "Cohen, B., Ruth, L. J., & Preuss, C. V. (2025)", + "title": "Opioid Analgesics. In StatPearls.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK459161/" + }, + { + "author": "Dargan, P. I., Sedefov, R., Gallegos, A., & Wood, D. M. (2011)", + "title": "The pharmacology and toxicology of the synthetic cathinone mephedrone (4‐methylmethcathinone). Drug Testing and Analysis, 3(7–8), 454–463.", + "url": "https://doi.org/10.1002/dta.312" + }, + { + "author": "Hadlock, G. C., Webb, K. M., McFadden, L. M., Chu, P. W., Ellis, J. D., Allen, S. C., Andrenyak, D. M., Vieira-Brock, P. L., German, C. L., Conrad, K. M., Hoonakker, A. J., Gibb, J. W., Wilkins, D. G., Hanson, G. R., & Fleckenstein, A. E. (2011)", + "title": "4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse. The Journal of Pharmacology and Experimental Therapeutics, 339(2), 530–536.", + "url": "https://doi.org/10.1124/jpet.111.184119" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T. (2011)", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats: Mephedrone increases both DA and 5-HT in rat brain. British Journal of Pharmacology, 164(8), 1949–1958.", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Meng, H., Cao, J., Kang, J., Ying, X., Ji, J., Reynolds, W., & Rampe, D. (2012)", + "title": "Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat. Toxicology Letters, 208(1), 62–68.", + "url": "https://doi.org/10.1016/j.toxlet.2011.10.010" + }, + { + "author": "Pathan, H., & Williams, J. (2012)", + "title": "Basic opioid pharmacology: an update. British Journal of Pain, 6(1), 11–16.", + "url": "https://doi.org/10.1177/2049463712438493" + } + ], + "status": "Caution" + }, + "mescaline": { + "status": "Low Risk & No Synergy" + }, + "mushrooms": { + "status": "Low Risk & No Synergy" + }, + "mxe": { + "note": "This combination can potentiate the effects of the opioid", + "status": "Dangerous" + }, + "nbomes": { + "status": "Low Risk & No Synergy" + }, + "nitrous": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are likely.", + "status": "Caution" + }, + "pcp": { + "note": "PCP can reduce opioid tolerance, increasing the risk of overdose", + "status": "Caution" + }, + "pregabalin": { + "sources": [ + { + "author": "Eckhardt, K., Ammon, S., Hofmann, U., Riebe, A., Gugeler, N., & Mikus, G. (2000)", + "title": "Gabapentin enhances the analgesic effect of morphine in healthy volunteers. Anesthesia and Analgesia, 91(1), 185–191.", + "url": "https://doi.org/10.1097/00000539-200007000-00035" + }, + { + "author": "Eipe, N., & Penning, J. (2011)", + "title": "Postoperative respiratory depression associated with pregabalin: A case series and a preoperative decision algorithm. Pain Research & Management: The Journal of the Canadian Pain Society, 16(5), 353–356.", + "url": "https://doi.org/10.1155/2011/561604" + }, + { + "author": "Elliott, S. P., Burke, T., & Smith, C. (2017)", + "title": "Determining the Toxicological Significance of Pregabalin in Fatalities. Journal of Forensic Sciences, 62(1), 169–173.", + "url": "https://doi.org/10.1111/1556-4029.13263" + }, + { + "author": "Evoy, K. E., Sadrameli, S., Contreras, J., Covvey, J. R., Peckham, A. M., & Morrison, M. D. (2021)", + "title": "Abuse and Misuse of Pregabalin and Gabapentin: A Systematic Review Update. Drugs, 81(1), 125–156.", + "url": "https://doi.org/10.1007/s40265-020-01432-7" + }, + { + "author": "Gomes, T., Juurlink, D. N., Antoniou, T., Mamdani, M. M., Paterson, J. M., & Brink, W. van den. (2017)", + "title": "Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case–control study. PLOS Medicine, 14(10), e1002396.", + "url": "https://doi.org/10.1371/journal.pmed.1002396" + }, + { + "author": "Lyndon, A., Audrey, S., Wells, C., Burnell, E. S., Ingle, S., Hill, R., Hickman, M., & Henderson, G. (2017)", + "title": "Risk to heroin users of polydrug use of pregabalin or gabapentin: Risks in combining gabapentoids with heroin. Addiction, 112(9), 1580–1589.", + "url": "https://doi.org/10.1111/add.13843" + }, + { + "author": "Peckham, A. M., Evoy, K. E., Covvey, J. R., Ochs, L., Fairman, K. A., & Sclar, D. A. (2018)", + "title": "Predictors of Gabapentin Overuse With or Without Concomitant Opioids in a Commercially Insured U.S. Population. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 38(4), 436–443.", + "url": "https://doi.org/10.1002/phar.2096" + }, + { + "author": "Research, C. for D. E. and. (2020)", + "title": "FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR). FDA.", + "url": "https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin" + } + ], + "status": "Dangerous" + }, + "ssris": { + "note": "There have been some case reports of serotonin syndrome in individuals who were given a combination of opioids and SSRIs. Other research has indicated a small increase in overdose risk for people who are prescribed CYP2D6-inhibiting SSRIs (e.g. fluoxetine and paroxetine) with oxycodone. Overall, risk is low with this combination but, as always, be mindful of your consumption.", + "status": "Low Risk & No Synergy" + }, + "tramadol": { + "note": "Concomitant use of tramadol increases the seizure risk in individuals taking other opioids. These agents are often individually epileptogenic and may have additive effects on seizure threshold during coadministration. Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present", + "status": "Dangerous" + } + }, + "pcp": { + "2c-t-x": { + "status": "Dangerous" + }, + "2c-x": { + "status": "Low Risk & Synergy" + }, + "5-meo-xxt": { + "status": "Dangerous" + }, + "alcohol": { + "note": "Details of this combination are not well understood but PCP generally interacts in an unpredictable manner.", + "status": "Unsafe" + }, + "amphetamines": { + "note": "This combination can easily lead to hypermanic states", + "status": "Unsafe" + }, + "amt": { + "status": "Dangerous" + }, + "benzodiazepines": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are likely", + "status": "Unsafe" + }, + "caffeine": { + "note": "Details of this combination are not well understood but PCP generally interacts in an unpredictable manner.", + "status": "Caution" + }, + "cannabis": { + "status": "Low Risk & Synergy" + }, + "cocaine": { + "note": "This combination can easily lead to hypermanic states", + "status": "Unsafe" + }, + "dextromethorphan": { + "status": "Dangerous" + }, + "dmt": { + "status": "Low Risk & Synergy" + }, + "dox": { + "note": "Details of this combination are not well understood but PCP generally interacts in an unpredictable manner.", + "status": "Unsafe" + }, + "ghb/gbl": { + "note": "Details of this combination are not well understood but PCP generally interacts in an unpredictable manner.", + "status": "Dangerous" + }, + "ketamine": { + "status": "Low Risk & Synergy" + }, + "lsd": { + "status": "Low Risk & Synergy" + }, + "maois": { + "note": "This combination is very poorly explored", + "status": "Dangerous" + }, + "mdma": { + "note": "This combination can easily lead to hypermanic states", + "status": "Unsafe" + }, + "mescaline": { + "status": "Low Risk & Synergy" + }, + "mushrooms": { + "status": "Low Risk & Synergy" + }, + "mxe": { + "note": "There are no reports available about this combination", + "status": "Caution" + }, + "nbomes": { + "status": "Low Risk & Synergy" + }, + "nitrous": { + "status": "Low Risk & Synergy" + }, + "opioids": { + "note": "PCP can reduce opioid tolerance, increasing the risk of overdose", + "status": "Caution" + }, + "ssris": { + "note": "Details of this combination are not well understood but PCP generally interacts in an unpredictable manner.", + "status": "Unsafe" + }, + "tramadol": { + "status": "Dangerous" + } + }, + "pregabalin": { + "2c-x": { + "note": "Pregabalin may reduce the anxiety and other possible side effects of 2C-X drugs. Additionally, the combination may increase inhibition, dizziness, and risk of injury.", + "sources": [ + { + "author": "Cross, A. L., Viswanath, O., & Sherman, A. L. (2025)", + "title": "Pregabalin. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK470341/" + }, + { + "author": "Gil-Martins, E., Barbosa, D. J., Borges, F., Remião, F., & Silva, R. (2025)", + "title": "Toxicodynamic insights of 2C and NBOMe drugs – Is there abuse potential? Toxicology Reports, 14, 101890.", + "url": "https://doi.org/10.1016/j.toxrep.2025.101890" + } + ], + "status": "Low Risk & Synergy" + }, + "5-meo-xxt": { + "note": "Caution should be given due to 5-MeO-xxT drugs stimulating effects and pregabalin’s seizure concerns at higher dosages. Pregabalin may reduce the vasoconstriction, anxiety, and other side effects of 5-MeO-xxT drugs. Additionally, Pregabalin may increase 5-MeO-xxT drugs inhibition and risk of injury.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Altuncı, Y. A., Aydoğdu, M., Açıkgöz, E., Güven, Ü., Düzağaç, F., Atasoy, A., Dağlıoğlu, N., & Akgür, S. A. (2021)", + "title": "New Psychoactive Substance 5-MeO-MiPT In vivo Acute Toxicity and Hystotoxicological Study. Balkan Medical Journal, 38(1), 34–42.", + "url": "https://doi.org/10.4274/balkanmedj.galenos.2020.2019.11.68" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Reckweg, J. T., Uthaug, M. V., Szabo, A., Davis, A. K., Lancelotta, R., Mason, N. L., & Ramaekers, J. G. (2022)", + "title": "The clinical pharmacology and potential therapeutic applications of 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeO‐DMT). Journal of Neurochemistry, 162(1), 128–146.", + "url": "https://doi.org/10.1111/jnc.15587" + }, + { + "author": "Rickli, A., Moning, O. D., Hoener, M. C., & Liechti, M. E. (2016)", + "title": "Receptor interaction profiles of novel psychoactive tryptamines compared with classic hallucinogens. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 26(8), 1327–1337.", + "url": "https://doi.org/10.1016/j.euroneuro.2016.05.001" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Soto-Angona, Ó., Fortea, A., Fortea, L., Martínez-Ramírez, M., Santamarina, E., López, F. J. G., Knudsen, G. M., & Ona, G. (2024)", + "title": "Do classic psychedelics increase the risk of seizures? A scoping review. European Neuropsychopharmacology, 85, 35–42.", + "url": "https://doi.org/10.1016/j.euroneuro.2024.05.002" + } + ], + "status": "Caution" + }, + "amphetamines": { + "note": "There is a significant risk of seizures from this combination. Amphetamines increase respiration rate allowing for a higher dose of sedatives than normal. If amphetamines wears off first, recreational dosages of pregabalin may overcome the individual and cause respiratory arrest. Both substances at recreational dosages cause strain of the heart and may lead to further dangerous heart complications.", + "sources": [ + { + "author": "Martin, D., & Le, J. K. (2023)", + "title": "Amphetamine. In StatPearls. StatPearls Publishing.", + "url": "https://www.ncbi.nlm.nih.gov/books/NBK556103/" + }, + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + } + ], + "status": "Unsafe" + }, + "caffeine": { + "note": "There is a risk of seizures from this combination, especially at higher dosages. Caffeine additionally reduces pregabalin’s anticonvulsant effects found in lower dosages. Caffeine increases respiration rate allowing for a higher dose of sedatives than normal. If amphetamines wears off first, recreational dosages of pregabalin may overcome the individual and cause respiratory arrest. Both substances at recreational dosages cause strain of the heart and may lead to further dangerous heart complications. Medical dosages are unlikely to be of concern.", + "sources": [ + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben‐Menachem, E. (2004)", + "title": "Pregabalin Pharmacology and Its Relevance to Clinical Practice. Epilepsia, 45(s6), 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Chwedorowicz, R., Łukawski, K., Raszewski, G., & Czuczwar, S. J. (2022)", + "title": "Effect of caffeine on the anticonvulsant action of pregabalin against electroconvulsions in mice. Pharmacological Reports: PR, 74(2), 431–437.", + "url": "https://doi.org/10.1007/s43440-022-00356-1" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures: A historical-controlled trial. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N., & Livingston, J. (2006)", + "title": "Aggravation of epilepsy by anti‐epileptic drugs. Developmental Medicine & Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Miziak, B., Błaszczyk, B., Chrościńska-Krawczyk, M., & Czuczwar, S. J. (2023)", + "title": "Caffeine and Its Interactions with Antiseizure Medications—Is There a Correlation between Preclinical and Clinical Data? International Journal of Molecular Sciences, 24(24), 17569.", + "url": "https://doi.org/10.3390/ijms242417569" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + } + ], + "status": "Unsafe" + }, + "cannabis": { + "note": "Both substances may increase each other's side effects, such as sedation, lowered blood pressure, and raised heart rate.", + "sources": [ + { + "author": "Balachandran, P., Elsohly, M., & Hill, K. P.", + "title": "Cannabidiol Interactions with Medications, Illicit Substances, and Alcohol: a Comprehensive Review (2021)", + "url": "https://doi.org/10.1007/s11606-020-06504-8" + }, + { + "author": "Klein, T. A., & Clark, C. S.", + "title": "Therapeutic use of cannabis in the US. The Nurse Practitioner, 47(12) (2022)", + "url": "https://doi.org/10.1097/01.NPR.0000884880.81603.c5" + }, + { + "author": "Lile, J. A., Alcorn, J. L., Hays, L. R., Kelly, T. H., Stoops, W. W., Wesley, M. J., & Westgate, P. M.", + "title": "Influence of Pregabalin Maintenance on Cannabis Effects and Related Behaviors in Daily Cannabis Users. Experimental and Clinical Psychopharmacology, 30(5) (2022)", + "url": "https://doi.org/10.1037/pha0000464" + }, + { + "author": "Vázquez, M., Guevara, N., Maldonado, C., Guido, P. C., & Schaiquevich, P.", + "title": "Potential Pharmacokinetic Drug‐Drug Interactions between Cannabinoids and Drugs Used for Chronic Pain (2020)", + "url": "https://doi.org/10.1155/2020/3902740" + } + ], + "status": "Low Risk & Synergy" + }, + "cocaine": { + "note": "There is a significant risk of seizures from this combination. Stimulants increase respiration rate, allowing for a higher dose of sedatives than normal. If cocaine wears off first, recreational dosages of pregabalin may overcome the individual and cause respiratory arrest. Both substances at recreational dosages strain the heart and may lead to further dangerous heart complications. The combination has a greater risk of methemoglobinemia when higher dosages are combined.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure: Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Hunter, L., Gordge, L., Dargan, P. I., & Wood, D. M. (2011)", + "title": "Methaemoglobinaemia associated with the use of cocaine and volatile nitrites as recreational drugs: a review. British Journal of Clinical Pharmacology, 72(1), 18–26.", + "url": "https://doi.org/10.1111/j.1365-2125.2011.03950.x" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Lappin, J. M., & Sara, G. E. (2019)", + "title": "Psychostimulant use and the brain. Addiction, 114(11), 2065–2077.", + "url": "https://doi.org/10.1111/add.14708" + }, + { + "author": "Ludlow, J. T., Wilkerson, R. G., & Nappe, T. M. (2025)", + "title": "Methemoglobinemia. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK537317/" + }, + { + "author": "Pergolizzi, J. V., Magnusson, P., LeQuang, J. A. K., Breve, F., & Varrassi, G. (n.d.)", + "title": "Cocaine and Cardiotoxicity: A Literature Review. Cureus, 13(4), e14594.", + "url": "https://doi.org/10.7759/cureus.14594" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + } + ], + "status": "Unsafe" + }, + "dextromethorphan": { + "note": "Pregabalin and DXM may increase each other’s effects such as inhibition, dizziness, sedation. At higher doses this can lead to unexpected loss of consciousness. Both drugs have seizure concerns which is greatly increased in combination.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Journey, J. D., Agrawal, S., & Stern, E. (2025)", + "title": "Dextromethorphan Toxicity. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK538502/" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Oh, S., Agrawal, S., Sabir, S., & Taylor, A. (2025)", + "title": "Dextromethorphan. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK538216/" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + } + ], + "status": "Unsafe" + }, + "diphenhydramine": { + "note": "There is a significant risk of seizures from this combination. The combination is likely to increase each other’s negative side effects, such as nausea, dizziness, and loss of consciousness. At higher dosages, pregabalin is likely to increase diphenhydramine’s deliriant effects, inhibition, and risk of injury. Medical dosages are not reported to be a concern.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Medline Plus Medical Encyclopedia (2023)", + "title": "Diphenhydramine overdose", + "url": "https://medlineplus.gov/ency/article/002636.htm" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "Fakhr, M. S., Motamed Chaboki, P., Ashayeri, H., Sahranavard, P., Mohammadipanah, S., & Zamanabadi, M. N. (2023)", + "title": "Comparison of the effects of pregabalin and famotidine with pregabalin and diphenhydramine on postoperative abdominal pain. International Journal of Surgery Open, 58, 100674.", + "url": "https://doi.org/10.1016/j.ijso.2023.100674" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Jang, D. H., Manini, A. F., Trueger, N. S., Duque, D., Nestor, N. B., Nelson, L. S., & Hoffman, R. S. (2010)", + "title": "Status epilepticus and wide-complex tachycardia secondary to diphenhydramine overdose. Clinical Toxicology, 48(9), 945–948.", + "url": "https://doi.org/10.3109/15563650.2010.527850" + }, + { + "author": "Kim, H., Kim, S. H., & Kim, J. B. (2021)", + "title": "Antihistamines as a common cause of new-onset seizures: a single-center observational study. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 42(6), 2505–2508.", + "url": "https://doi.org/10.1007/s10072-021-05043-2" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Schifano, F., Chiappini, S., Miuli, A., Mosca, A., Santovito, M. C., Corkery, J. M., Guirguis, A., Pettorruso, M., Di Giannantonio, M., & Martinotti, G. (2021)", + "title": "Focus on Over-the-Counter Drugs’ Misuse: A Systematic Review on Antihistamines, Cough Medicines, and Decongestants. Frontiers in Psychiatry, 12, 657397.", + "url": "https://doi.org/10.3389/fpsyt.2021.657397" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Wolfson, A. R., Wong, D., Abrams, E. M., Waserman, S., & Sussman, G. L. (2022)", + "title": "Diphenhydramine: Time to Move on? The Journal of Allergy and Clinical Immunology: In Practice, 10(12), 3124–3130.", + "url": "https://doi.org/10.1016/j.jaip.2022.07.018" + } + ], + "status": "Unsafe" + }, + "dmt": { + "note": "Pregabalin may reduce the anxiety and other possible side effects of DMT. Additionally, the combination may increase inhibition, dizziness, and risk of injury.", + "sources": [ + { + "author": "Carbonaro, T. M., & Gatch, M. B. (2016)", + "title": "Neuropharmacology of N,N-Dimethyltryptamine. Brain Research Bulletin, 126(Pt 1), 74–88.", + "url": "https://doi.org/10.1016/j.brainresbull.2016.04.016" + }, + { + "author": "Cross, A. L., Viswanath, O., & Sherman, A. L. (2025)", + "title": "Pregabalin. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK470341/" + } + ], + "status": "Low Risk & Synergy" + }, + "dox": { + "note": "Caution should be given due to DOx drugs stimulating effects and pregabalin’s seizure concerns at higher dosages. Pregabalin may reduce the vasoconstriction, anxiety, and other side effects of DOx drugs. Additionally, Pregabalin may increase DOx drugs inhibition and risk of injury.", + "sources": [ + { + "author": "ScienceDirect Topics (n.d.)", + "title": "2,5-Dimethoxy-4-iodoamphetamine - an overview", + "url": "https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/2-5-dimethoxy-4-iodoamphetamine" + }, + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Barnett, R. Y., Baker, D. D., Kelly, N. E., McGuire, C. E., Fassette, T. C., & Gorniak, J. M. (2014)", + "title": "A Fatal Intoxication of 2,5-Dimethoxy-4-Chloroamphetamine: A Case Report. Journal of Analytical Toxicology, 38(8), 589–591.", + "url": "https://doi.org/10.1093/jat/bku087" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Burish, M. J., Thoren, K. L., Madou, M., Toossi, S., & Shah, M. (2015)", + "title": "Hallucinogens Causing Seizures? A Case Report of the Synthetic Amphetamine 2,5-Dimethoxy-4-Chloroamphetamine. The Neurohospitalist, 5(1), 32–34.", + "url": "https://doi.org/10.1177/1941874414528939" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Jacob, P., & Shulgin, A. T. (1994)", + "title": "Structure-activity relationships of the classic hallucinogens and their analogs. NIDA Research Monograph, 146, 74–91.", + "url": "https://pubmed.ncbi.nlm.nih.gov/8742795/" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Luethi, D., Rudin, D., Hoener, M. C., & Liechti, M. E. (2022)", + "title": "Monoamine Receptor and Transporter Interaction Profiles of 4‐Alkyl‐Substituted 2,5‐Dimethoxyamphetamines. The FASEB Journal, 36(S1), fasebj.2022.36.S1.R2691.", + "url": "https://doi.org/10.1096/fasebj.2022.36.S1.R2691" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Trout, K., & Daley, P. F. (2024)", + "title": "The origin of 2,5‐dimethoxy‐4‐methylamphetamine (DOM, STP). Drug Testing and Analysis, 16(12), 1496–1508.", + "url": "https://doi.org/10.1002/dta.3667" + } + ], + "status": "Caution" + }, + "ghb/gbl": { + "note": "The two substances potentiate each other strongly and unpredictably, and may rapidly lead to unconsciousness. They both increase each other's side effects such as ataxia, sedation, and CNS depression. Blackout and memory loss risk is significantly increased. If the user falls unconscious while under the influence there is a severe risk of vomit aspiration if they are not placed in the recovery position. There is an increased risk of seizures from this combination.", + "sources": [ + { + "author": "Cagnin, A., Pompanin, S., Manfioli, V., Briani, C., Zambon, A., Saladini, M., & Dam, M. (2011)", + "title": "γ-Hydroxybutyric acid-induced psychosis and seizures.", + "url": "https://doi.org/10.1016/j.yebeh.2011.03.009" + }, + { + "author": "Castelli, M. P., Ferraro, L., Mocci, I., Carta, F., Carai, M. A. M., Antonelli, T., Tanganelli, S., Cignarella, G., & Gessa, G. L. (2003)", + "title": "Selective γ‐hydroxybutyric acid receptor ligands increase extracellular glutamate in the hippocampus, but fail to activate G protein and to produce the sedative/hypnotic effect of γ‐hydroxybutyric acid.", + "url": "https://doi.org/10.1046/j.1471-4159.2003.02037.x" + }, + { + "author": "Eipe, N., & Penning, J. (2011)", + "title": "Postoperative Respiratory Depression Associated with Pregabalin: A Case Series and a Preoperative Decision Algorithm.", + "url": "https://doi.org/10.1155/2011/561604" + }, + { + "author": "Elliott, S. P., Burke, T., & Smith, C. (2017)", + "title": "Determining the Toxicological Significance of Pregabalin in Fatalities.", + "url": "https://doi.org/10.1111/1556-4029.13263" + }, + { + "author": "Evoy, K. E., Sadrameli, S., Contreras, J., Covvey, J. R., Peckham, A. M., & Morrison, M. D. (2021)", + "title": "Abuse and Misuse of Pregabalin and Gabapentin: A Systematic Review Update.", + "url": "https://doi.org/10.1007/s40265-020-01432-7" + }, + { + "author": "Galloway, G. P., Frederick, S. L., Staggers, F. E., Gonzales, M., Stalcup, S. A., & Smith, D. E. (1997)", + "title": "Gamma-hydroxybutyrate: an emerging drug of abuse that causes physical dependence.", + "url": "https://pubmed.ncbi.nlm.nih.gov/9060200/" + }, + { + "author": "Le, J. K., & Richards, J. R. (2025a)", + "title": "Gamma-Hydroxybutyrate Toxicity. In StatPearls.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK430781/" + }, + { + "author": "Le, J. K., & Richards, J. R. (2025b)", + "title": "Gamma-Hydroxybutyrate Toxicity. In StatPearls.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK430781/" + }, + { + "author": "Oskouei, Z., Moshiri, M., Raouf-Rahmati, A., Nemati, A., Bemani Naeini, M., Jomehpour, H., Roohbakhsh, A., Salmasi, Z., & Etemad, L. (2025)", + "title": "Seizures as an Adverse Effect of Pregabalin Consumption: A Systematic Review.", + "url": "https://doi.org/10.34172/ahj.1527" + }, + { + "author": "Venzi, M., Di Giovanni, G., & Crunelli, V. (2014)", + "title": "A Critical Evaluation of the Gamma‐Hydroxybutyrate (GHB) Model of Absence Seizures.", + "url": "https://doi.org/10.1111/cns.12337" + }, + { + "author": "Winters, W. D., & Spooner, C. E. (1965)", + "title": "Various seizure activities following gamma-hydroxybutyrate.", + "url": "https://doi.org/10.1016/0028-3908(65)90034-1" + } + ], + "status": "Dangerous" + }, + "ketamine": { + "note": "Pregabalin and ketamine may synergize and increase each other's negative side effects such as nausea, dizziness, and loss of consciousness. Caution is advised for beyond medical dosages due to seizure concerns, and medical dosages for individuals with higher risk seizure profiles and or behavior.", + "sources": [ + { + "author": "Anwar, S., Cooper, J., Rahman, J., Sharma, C., & Langford, R. (2019)", + "title": "Prolonged Perioperative Use of Pregabalin and Ketamine to Prevent Persistent Pain after Cardiac Surgery. Anesthesiology, 131(1), 119–131.", + "url": "https://doi.org/10.1097/ALN.0000000000002751" + }, + { + "author": "Arendt-Nielsen, L., Mansikka, H., Staahl, C., Rees, H., Tan, K., Smart, T. S., Monhemius, R., Suzuki, R., & Drewes, A. M. (2011)", + "title": "A Translational Study of the Effects of Ketamine and Pregabalin on Temporal Summation of Experimental Pain. Regional Anesthesia & Pain Medicine, 36(6), 585–591.", + "url": "https://doi.org/10.1097/AAP.0b013e31822b0db0" + }, + { + "author": "Az, A., & Doğan, Y. (2024)", + "title": "Unexpected consequences: A case of ketamine‑induced seizure in procedural sedation. Turkish Journal of Emergency Medicine, 24(4), 259–261.", + "url": "https://doi.org/10.4103/tjem.tjem_67_24" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben‐Menachem, E. (2004)", + "title": "Pregabalin Pharmacology and Its Relevance to Clinical Practice. Epilepsia, 45(s6), 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures: A historical-controlled trial. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N., & Livingston, J. (2006)", + "title": "Aggravation of epilepsy by anti‐epileptic drugs. Developmental Medicine & Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kim, J. H., Lee, C. K., Yu, S. H., Min, B. D., Chung, C. E., & Kim, D. C. (2021)", + "title": "Ketamine-induced generalized convulsive seizure during procedural sedation. Archives of Craniofacial Surgery, 22(2), 119–121.", + "url": "https://doi.org/10.7181/acfs.2021.00094" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Martinez, V., Cymerman, A., Ben Ammar, S., Fiaud, J. F., Rapon, C., Poindessous, F., Judet, T., Chauvin, M., Bouhassira, D., Sessler, D., Mazoit, X., & Fletcher, D. (2014)", + "title": "The analgesic efficiency of combined pregabalin and ketamine for total hip arthroplasty: a randomised, double‐blind, controlled study. Anaesthesia, 69(1), 46–52.", + "url": "https://doi.org/10.1111/anae.12495" + }, + { + "author": "Shehata, I. M., Kohaf, N. A., ElSayed, M. W., Latifi, K., Aboutaleb, A. M., & Kaye, A. D. (2024)", + "title": "Ketamine: Pro or antiepileptic agent? A systematic review. Heliyon, 10(2), e24433.", + "url": "https://doi.org/10.1016/j.heliyon.2024.e24433" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Zhou, Y., Sun, W., Fu, Y., Wang, J., Fan, J., Liang, Y., Jia, W., & Han, R. (2024)", + "title": "Effect of esketamine combined with pregabalin on acute postsurgical pain in patients who underwent resection of spinal neoplasms: a randomized controlled trial. Pain, 165(9), e96–e105.", + "url": "https://doi.org/10.1097/j.pain.0000000000003211" + } + ], + "status": "Caution" + }, + "lsd": { + "note": "Caution should be given due to LSD’s stimulating effects and pregabalin’s seizure concerns at higher dosages. Pregabalin may reduce the vasoconstriction, anxiety, and other side effects of LSD. Additionally, Pregabalin may increase LSD’s inhibition and risk of injury.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Baquiran, M., Keyes, D., & Al Khalili, Y. (2025)", + "title": "Lysergic Acid Diethylamide Toxicity. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK553216/" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Soto-Angona, Ó., Fortea, A., Fortea, L., Martínez-Ramírez, M., Santamarina, E., López, F. J. G., Knudsen, G. M., & Ona, G. (2024)", + "title": "Do classic psychedelics increase the risk of seizures? A scoping review. European Neuropsychopharmacology, 85, 35–42.", + "url": "https://doi.org/10.1016/j.euroneuro.2024.05.002" + } + ], + "status": "Caution" + }, + "mdma": { + "note": "There is a significant risk of seizures from this combination. Amphetamines increase respiration rate allowing for a higher dose of sedatives than normal. If amphetamines wears off first, recreational dosages of pregabalin may overcome the individual and cause respiratory arrest. Both substances at recreational dosages cause strain of the heart and may lead to further dangerous heart complications. Medical dosages are not reported to be a concern", + "sources": [ + { + "author": "Alo, C., & Kioka, M. J. (2024)", + "title": "Rave gone wrong: MDMA- induced medical emergency at electrical daisy carnival. A case report. Toxicology Reports, 13, 101739.", + "url": "https://doi.org/10.1016/j.toxrep.2024.101739" + }, + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Christie, D., Yazar-Klosinski, B., Nosova, E., Kryskow, P., Siu, W., Lessor, D., & Argento, E. (2022)", + "title": "MDMA-assisted therapy is associated with a reduction in chronic pain among people with post-traumatic stress disorder. Frontiers in Psychiatry, 13.", + "url": "https://doi.org/10.3389/fpsyt.2022.939302" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Oskouei, Z., Moshiri, M., Raouf-Rahmati, A., Nemati, A., Bemani Naeini, M., Jomehpour, H., Roohbakhsh, A., Salmasi, Z., & Etemad, L. (2025)", + "title": "Seizures as an Adverse Effect of Pregabalin Consumption: A Systematic Review. Addiction & Health, 17, 1527.", + "url": "https://doi.org/10.34172/ahj.1527" + }, + { + "author": "Rietjens, S. J., Sikma, M. A., Hunault, C. C., De Lange, D. W., & Hondebrink, L. (2022)", + "title": "Pregabalin poisoning: Evaluation of dose‐toxicity relationship. British Journal of Clinical Pharmacology, 88(3), 1288–1297.", + "url": "https://doi.org/10.1111/bcp.15073" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Vollenweider, F. X., Gamma, A., Liechti, M., & Huber, T. (1998)", + "title": "Psychological and cardiovascular effects and short-term sequelae of MDMA (“ecstasy”) in MDMA-naïve healthy volunteers. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 19(4), 241–251.", + "url": "https://doi.org/10.1016/S0893-133X(98)00013-X" + } + ], + "status": "Unsafe" + }, + "mephedrone": { + "note": "There is a significant risk of seizures from this combination. Mephedrone increases respiration rate allowing for a higher dose of sedatives than normal. If mephedrone wears off first, recreational dosages of pregabalin may overcome the individual and cause respiratory arrest. Both substances at recreational dosages cause strain of the heart and may lead to further dangerous heart complications.", + "sources": [ + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben‐Menachem, E. (2004)", + "title": "Pregabalin Pharmacology and Its Relevance to Clinical Practice. Epilepsia, 45(s6), 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Dargan, P. I., Sedefov, R., Gallegos, A., & Wood, D. M. (2011)", + "title": "The pharmacology and toxicology of the synthetic cathinone mephedrone (4‐methylmethcathinone). Drug Testing and Analysis, 3(7–8), 454–463.", + "url": "https://doi.org/10.1002/dta.312" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures: A historical-controlled trial. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N., & Livingston, J. (2006)", + "title": "Aggravation of epilepsy by anti‐epileptic drugs. Developmental Medicine & Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Altair. (n.d)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T. (2011)", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats: Mephedrone increases both DA and 5-HT in rat brain. British Journal of Pharmacology, 164(8), 1949–1958.", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Meng, H., Cao, J., Kang, J., Ying, X., Ji, J., Reynolds, W., & Rampe, D. (2012)", + "title": "Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat. Toxicology Letters, 208(1), 62–68.", + "url": "https://doi.org/10.1016/j.toxlet.2011.10.010" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + } + ], + "status": "Unsafe" + }, + "mescaline": { + "note": "Caution should be given due to mescaline’s stimulating effects and pregabalin’s seizure concerns at higher dosages. Pregabalin may reduce the vasoconstriction, anxiety, and other side effects of mescaline. Additionally, Pregabalin may increase mescaline’s inhibition and risk of injury.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "Freidel, N., Kreuder, L., Rabinovitch, B. S., Chen, F. Y., Huang, R. S. T., & Lewis, E. C. (2024)", + "title": "Psychedelics, epilepsy, and seizures: a review. Frontiers in Pharmacology, 14.", + "url": "https://doi.org/10.3389/fphar.2023.1326815" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures: A historical-controlled trial. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Simonsson, O., Goldberg, S. B., Chambers, R., Osika, W., Long, D. M., & Hendricks, P. S. (2022)", + "title": "Prevalence and associations of classic psychedelic-related seizures in a population-based sample. Drug and Alcohol Dependence, 239, 109586.", + "url": "https://doi.org/10.1016/j.drugalcdep.2022.109586" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Soto-Angona, Ó., Fortea, A., Fortea, L., Martínez-Ramírez, M., Santamarina, E., López, F. J. G., Knudsen, G. M., & Ona, G. (2024)", + "title": "Do classic psychedelics increase the risk of seizures? A scoping review. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology, 85, 35–42.", + "url": "https://doi.org/10.1016/j.euroneuro.2024.05.002" + } + ], + "status": "Caution" + }, + "mushrooms": { + "note": "Pregabalin may reduce the anxiety and other possible side effects of Psilocybin Mushrooms. Additionally, the combination may increase inhibition, dizziness, and risk of injury.", + "sources": [ + { + "author": "Cross, A. L., Viswanath, O., & Sherman, A. L. (2025)", + "title": "Pregabalin. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK470341/" + }, + { + "author": "ScienceDirect Topics. (n.d.)", + "title": "Psilocybin - an overview", + "url": "https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/psilocybin" + } + ], + "status": "Low Risk & Synergy" + }, + "mxe": { + "note": "Pregabalin and MXE may synergize and increase each other’s negative side effects such as nausea, dizziness, and loss of consciousness. Caution is advised for anything above low dosages due to seizure concerns, and all dosages for individuals with higher risk seizure profiles and or behavior.", + "sources": [ + { + "author": "Anwar, S., Cooper, J., Rahman, J., Sharma, C., & Langford, R. (2019)", + "title": "Prolonged Perioperative Use of Pregabalin and Ketamine to Prevent Persistent Pain after Cardiac Surgery. Anesthesiology, 131(1), 119–131.", + "url": "https://doi.org/10.1097/ALN.0000000000002751" + }, + { + "author": "Arendt-Nielsen, L., Mansikka, H., Staahl, C., Rees, H., Tan, K., Smart, T. S., Monhemius, R., Suzuki, R., & Drewes, A. M. (2011)", + "title": "A Translational Study of the Effects of Ketamine and Pregabalin on Temporal Summation of Experimental Pain: Regional Anesthesia and Pain Medicine, 36(6), 585–591.", + "url": "https://doi.org/10.1097/AAP.0b013e31822b0db0" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben‐Menachem, E. (2004)", + "title": "Pregabalin Pharmacology and Its Relevance to Clinical Practice. Epilepsia, 45(s6), 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures: A historical-controlled trial. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N., & Livingston, J. (2006)", + "title": "Aggravation of epilepsy by anti‐epileptic drugs. Developmental Medicine & Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–552.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Marti, M., Talani, G., Miliano, C., Bilel, S., Biggio, F., Bratzu, J., Diana, M., De Luca, M. A., & Fattore, L. (2021)", + "title": "New insights into methoxetamine mechanisms of action: Focus on serotonergic 5-HT2 receptors in pharmacological and behavioral effects in the rat. Experimental Neurology, 345, 113836.", + "url": "https://doi.org/10.1016/j.expneurol.2021.113836" + }, + { + "author": "Martinez, V., Cymerman, A., Ben Ammar, S., Fiaud, J. F., Rapon, C., Poindessous, F., Judet, T., Chauvin, M., Bouhassira, D., Sessler, D., Mazoit, X., & Fletcher, D. (2014)", + "title": "The analgesic efficiency of combined pregabalin and ketamine for total hip arthroplasty: a randomised, double‐blind, controlled study. Anaesthesia, 69(1), 46–52.", + "url": "https://doi.org/10.1111/anae.12495" + }, + { + "author": "Roth, B. L., Gibbons, S., Arunotayanun, W., Huang, X.-P., Setola, V., Treble, R., & Iversen, L. (2013)", + "title": "The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor. PLoS ONE, 8(3), e59334.", + "url": "https://doi.org/10.1371/journal.pone.0059334" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Zhou, Y., Sun, W., Fu, Y., Wang, J., Fan, J., Liang, Y., Jia, W., & Han, R. (2024)", + "title": "Effect of esketamine combined with pregabalin on acute postsurgical pain in patients who underwent resection of spinal neoplasms: a randomized controlled trial. Pain, 165(9), e96–e105.", + "url": "https://doi.org/10.1097/j.pain.0000000000003211" + } + ], + "status": "Caution" + }, + "nbomes": { + "note": "NBOMes and pregabalin are reported to have significant seizure concerns that are likely to increase in combination. Therapeutic dosages of pregabalin are unlikely to be of concern and may decrease NBOMes side effects such as vasoconstriction and anxiety.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N. A., & Livingston, J. H. (2006)", + "title": "Aggravation of epilepsy by anti-epileptic drugs. Developmental Medicine and Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Kyriakou, C., Marinelli, E., Frati, P., Santurro, A., Afxentiou, M., Zaami, S., & Busardo, F. P. (2015)", + "title": "NBOMe: new potent hallucinogens--pharmacology, analytical methods, toxicities, fatalities: a review. European Review for Medical and Pharmacological Sciences, 19(17), 3270–3281.", + "url": "https://pubmed.ncbi.nlm.nih.gov/26400534/" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Zawilska, J. B., Kacela, M., & Adamowicz, P. (2020)", + "title": "NBOMes–Highly Potent and Toxic Alternatives of LSD. Frontiers in Neuroscience, 14, 78.", + "url": "https://doi.org/10.3389/fnins.2020.00078" + } + ], + "status": "Dangerous" + }, + "nitrous": { + "note": "Both substances potentiate the ataxia and sedation caused by the other, and may increase the risk of loss of consciousness at higher dosages. While unconscious, vomit aspiration is a risk if not placed in the recovery position. The combination may increase inhibition and risk of injury. Additionally, abuse of nitrous while under the influence of pregabalin may increase the risk of seizures. Medical dosages are unlikely to be a concern.", + "sources": [ + { + "author": "Barker-Haliski, M., & White, H. S. (2015)", + "title": "Glutamatergic Mechanisms Associated with Seizures and Epilepsy. Cold Spring Harbor Perspectives in Medicine, 5(8), a022863.", + "url": "https://doi.org/10.1101/cshperspect.a022863" + }, + { + "author": "Ben‐Menachem, E. (2004)", + "title": "Pregabalin Pharmacology and Its Relevance to Clinical Practice. Epilepsia, 45(s6), 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Cross, A. L., Viswanath, O., & Sherman, A. L. (2025)", + "title": "Pregabalin. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK470341/" + }, + { + "author": "Davidson, L. T. (2023)", + "title": "Recreational use of nitrous oxide causes seizure, pneumothorax, pneumomediastinum, and pneumopericardium: nitrous oxide and its harm, a case report. Upsala Journal of Medical Sciences, 128, 10.48101/ujms.v128.10281.", + "url": "https://doi.org/10.48101/ujms.v128.10281" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures: A historical-controlled trial. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Gayatri, N., & Livingston, J. (2006)", + "title": "Aggravation of epilepsy by anti‐epileptic drugs. Developmental Medicine & Child Neurology, 48(5), 394–398.", + "url": "https://doi.org/10.1017/S0012162206000843" + }, + { + "author": "Hitchings, A. W. (2016)", + "title": "Drugs that lower the seizure threshold. Adverse Drug Reaction Bulletin, 298(1), 1151–1154.", + "url": "https://doi.org/10.1097/FAD.0000000000000016" + }, + { + "author": "Isoardi, K. Z., Polkinghorne, G., Harris, K., & Isbister, G. K. (2020)", + "title": "Pregabalin poisoning and rising recreational use: a retrospective observational series. British Journal of Clinical Pharmacology, 86(12), 2435–2440.", + "url": "https://doi.org/10.1111/bcp.14348" + }, + { + "author": "Knuf, K., & Maani, C. V. (2025)", + "title": "Nitrous Oxide. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK532922/" + }, + { + "author": "Kumar, N., Laferriere, A., Yu, J. S. C., Leavitt, A., & Coderre, T. J. (2010)", + "title": "Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. Journal of Neurochemistry, 113(2), 552–561.", + "url": "https://doi.org/10.1111/j.1471-4159.2010.06625.x" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + }, + { + "author": "Wagner, S., Clark, M., Wesche, D., Doedens, D., & Lloyd, A. (1992)", + "title": "Asphyxial Deaths from the Recreational Use of Nitrous Oxide. Journal of Forensic Sciences, 37(4), 1008–1015.", + "url": "https://doi.org/10.1520/JFS13286J" + } + ], + "status": "Caution" + }, + "opioids": { + "sources": [ + { + "author": "Eckhardt, K., Ammon, S., Hofmann, U., Riebe, A., Gugeler, N., & Mikus, G. (2000)", + "title": "Gabapentin enhances the analgesic effect of morphine in healthy volunteers. Anesthesia and Analgesia, 91(1), 185–191.", + "url": "https://doi.org/10.1097/00000539-200007000-00035" + }, + { + "author": "Eipe, N., & Penning, J. (2011)", + "title": "Postoperative respiratory depression associated with pregabalin: A case series and a preoperative decision algorithm. Pain Research & Management: The Journal of the Canadian Pain Society, 16(5), 353–356.", + "url": "https://doi.org/10.1155/2011/561604" + }, + { + "author": "Elliott, S. P., Burke, T., & Smith, C. (2017)", + "title": "Determining the Toxicological Significance of Pregabalin in Fatalities. Journal of Forensic Sciences, 62(1), 169–173.", + "url": "https://doi.org/10.1111/1556-4029.13263" + }, + { + "author": "Evoy, K. E., Sadrameli, S., Contreras, J., Covvey, J. R., Peckham, A. M., & Morrison, M. D. (2021)", + "title": "Abuse and Misuse of Pregabalin and Gabapentin: A Systematic Review Update. Drugs, 81(1), 125–156.", + "url": "https://doi.org/10.1007/s40265-020-01432-7" + }, + { + "author": "Gomes, T., Juurlink, D. N., Antoniou, T., Mamdani, M. M., Paterson, J. M., & Brink, W. van den. (2017)", + "title": "Gabapentin, opioids, and the risk of opioid-related death: A population-based nested case–control study. PLOS Medicine, 14(10), e1002396.", + "url": "https://doi.org/10.1371/journal.pmed.1002396" + }, + { + "author": "Lyndon, A., Audrey, S., Wells, C., Burnell, E. S., Ingle, S., Hill, R., Hickman, M., & Henderson, G. (2017)", + "title": "Risk to heroin users of polydrug use of pregabalin or gabapentin: Risks in combining gabapentoids with heroin. Addiction, 112(9), 1580–1589.", + "url": "https://doi.org/10.1111/add.13843" + }, + { + "author": "Peckham, A. M., Evoy, K. E., Covvey, J. R., Ochs, L., Fairman, K. A., & Sclar, D. A. (2018)", + "title": "Predictors of Gabapentin Overuse With or Without Concomitant Opioids in a Commercially Insured U.S. Population. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 38(4), 436–443.", + "url": "https://doi.org/10.1002/phar.2096" + }, + { + "author": "Research, C. for D. E. and. (2020)", + "title": "FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR). FDA.", + "url": "https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns-about-serious-breathing-problems-seizure-and-nerve-pain-medicines-gabapentin-neurontin" + } + ], + "status": "Dangerous" + }, + "tramadol": { + "note": "There is a significant risk of seizures. Both substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and unconsciousness. The interaction will cause greater inhibition and risk of injury. If the user falls unconscious it is strongly recommended to put them into the recovery position and monitor breathing. Medical dosages are not reported to be a concern.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Boostani, R., & Derakhshan, S. (2012)", + "title": "Tramadol induced seizure: A 3-year study. Caspian Journal of Internal Medicine, 3(3), 484–487.", + "url": "https://pubmed.ncbi.nlm.nih.gov/24009919/" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Hassamal, S., Miotto, K., Dale, W., & Danovitch, I. (2018)", + "title": "Tramadol: Understanding the Risk of Serotonin Syndrome and Seizures. The American Journal of Medicine, 131(11), 1382.e1-1382.e6.", + "url": "https://doi.org/10.1016/j.amjmed.2018.04.025" + }, + { + "author": "Lyndon, A., Audrey, S., Wells, C., Burnell, E. S., Ingle, S., Hill, R., Hickman, M., & Henderson, G. (2017)", + "title": "Risk to heroin users of polydrug use of pregabalin or gabapentin: Risks in combining gabapentoids with heroin. Addiction, 112(9), 1580–1589.", + "url": "https://doi.org/10.1111/add.13843" + }, + { + "author": "Rietjens, S. J., Sikma, M. A., Hunault, C. C., De Lange, D. W., & Hondebrink, L. (2022)", + "title": "Pregabalin poisoning: Evaluation of dose‐toxicity relationship. British Journal of Clinical Pharmacology, 88(3), 1288–1297.", + "url": "https://doi.org/10.1111/bcp.15073" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + } + ], + "status": "Unsafe" + } + }, + "ssris": { + "2c-t-x": { + "status": "Low Risk & Decrease" + }, + "2c-x": { + "status": "Low Risk & Decrease" + }, + "5-meo-xxt": { + "status": "Low Risk & Decrease" + }, + "alcohol": { + "note": "Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.", + "status": "Caution" + }, + "amphetamines": { + "status": "Low Risk & No Synergy" + }, + "amt": { + "status": "Dangerous" + }, + "benzodiazepines": { + "status": "Low Risk & No Synergy" + }, + "caffeine": { + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "status": "Low Risk & No Synergy" + }, + "cocaine": { + "note": "May reduce each others' effectiveness. Cocaine can reduce mental stability and therefore exacerbate conditions which SSRIs are used to treat.", + "status": "Low Risk & No Synergy" + }, + "dextromethorphan": { + "note": "High risk of serotonin syndrome.", + "status": "Dangerous" + }, + "diphenhydramine": { + "note": "There is a high risk of serotonin syndrome at recreational dosages. Medical dosages are reported not to be a concern for the general population. The combination may increase each other's side effects, such as dizziness and drowsiness.", + "sources": [ + { + "author": "Clark, J. H., Meltzer, E. O., & Naclerio, R. M.", + "title": "Diphenhydramine: It is time to say a final goodbye. The World Allergy Organization Journal, 18(2), 101027 (2025)", + "url": "https://doi.org/10.1016/j.waojou.2025.101027" + }, + { + "author": "Ener, R. A., Meglathery, S. B., Decker, W. A. V., & Gallagher, R. M.", + "title": "Serotonin Syndrome and Other Serotonergic Disorders: Table 1. Pain Medicine, 4(1), 63-74 (2003)", + "url": "https://doi.org/10.1046/j.1526-4637.2003.03005.x" + }, + { + "author": "Khan, S., Saud, S., Khan, I., Asif, M., Ismail, O., Salam, A., Yang, T. J., & Norville, K. J.", + "title": "Serotonin Syndrome Presenting with Concomitant Tramadol and Diphenhydramine Use: A Case Report of an Unlikely Side-Effect. Cureus, 10(4), e2421 (2018)", + "url": "https://doi.org/10.7759/cureus.2421" + }, + { + "author": "Lane, R., Baldwin, D., & Preskorn, S.", + "title": "The SSRIs: advantages, disadvantages and differences. Journal of Psychopharmacology, 9(2 Suppl), 163-178 (1995)", + "url": "https://doi.org/10.1177/0269881195009002011" + }, + { + "author": "Sproule, B. A., Naranjo, C. A., Brenmer, K. E., & Hassan, P. C.", + "title": "Selective serotonin reuptake inhibitors and CNS drug interactions. A critical review of the evidence. Clinical Pharmacokinetics, 33(6), 454-471 (1997)", + "url": "https://doi.org/10.2165/00003088-199733060-00004" + }, + { + "author": "van Harten, J.", + "title": "Clinical pharmacokinetics of selective serotonin reuptake inhibitors. Clinical Pharmacokinetics, 24(3), 203-220 (1993)", + "url": "https://doi.org/10.2165/00003088-199324030-00003" + }, + { + "author": "Varghese, E., Abate, M. A., Hu, L., Kaplan, J., Kraner, J., Long, D. L., Sorg, M., Mock, A., Greenwald, M., & Andrew, T.", + "title": "Characterization of Diphenhydramine-Related Accidental Overdose Deaths. Academic Forensic Pathology, 5(1), 105-115 (2015)", + "url": "https://doi.org/10.23907/2015.011" + } + ], + "status": "Dangerous" + }, + "dmt": { + "status": "Low Risk & Decrease" + }, + "dox": { + "status": "Low Risk & Decrease" + }, + "ghb/gbl": { + "status": "Low Risk & No Synergy" + }, + "ketamine": { + "status": "Low Risk & No Synergy" + }, + "lithium": { + "note": "This interaction is used in medical settings without reported issues. If this combination is taken, caution would be recommended if any other drugs are planned to be taken on top of these that may have serotonergic activity.", + "sources": [ + { + "author": "Finley, P. R.", + "title": "Drug Interactions with Lithium: An Update. (2016)", + "url": "https://doi.org/10.1007/s40262-016-0370-y" + }, + { + "author": "Hawley CJ, Loughlin PJ, Quick SJ, Gale TM, Sivakumaran T, Hayes J, McPhee S.", + "title": "Efficacy, safety and tolerability of combined administration of lithium and selective serotonin reuptake inhibitors: a review of the current evidence. (2000)", + "url": "https://doi.org/10.1097/00004850-200015040-00002" + }, + { + "author": "Müller-Oerlinghausen, B.", + "title": "Drug Interactions with Lithium. (1999)", + "url": "https://doi.org/10.2165/00023210-199911010-00004" + }, + { + "author": "Bauer, Michael PhD, MD; Linden, Michael MD; Schaaf, Berthold; Weber, Hans J. MD.", + "title": "Adverse Events and Tolerability of the Combination of Fluoxetine/Lithium Compared With Fluoxetine. (1996)", + "url": "https://doi.org/10.1097/00004714-199604000-00005" + } + ], + "status": "Low Risk & No Synergy" + }, + "lsd": { + "status": "Low Risk & Decrease" + }, + "maois": { + "status": "Dangerous" + }, + "mdma": { + "sources": [ + { + "author": "Feduccia, A. A., Jerome, L., Mithoefer, M. C., & Holland, J.", + "title": "Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapy.", + "url": "https://doi.org/10.1007/s00213-020-05710-w" + }, + { + "author": "Sarparast, A., Thomas, K., Malcolm, B., & Stauffer, C. S.", + "title": "Drug-drug interactions between psychiatric medications and MDMA or psilocybin: a systematic review.", + "url": "https://doi.org/10.1007/s00213-022-06083-y" + }, + { + "author": "Malcolm, B., & Thomas, K. ", + "title": "Serotonin toxicity of serotonergic psychedelics.", + "url": "https://doi.org/10.1007/s00213-021-05876-x" + } + ], + "status": "Low Risk & Decrease" + }, + "mescaline": { + "status": "Low Risk & Decrease" + }, + "mushrooms": { + "status": "Low Risk & Decrease" + }, + "mxe": { + "note": "Depending on the SSRI this combination can be unpredictable", + "status": "Caution" + }, + "nbomes": { + "status": "Low Risk & Decrease" + }, + "nitrous": { + "status": "Low Risk & No Synergy" + }, + "opioids": { + "note": "There have been some case reports of serotonin syndrome in individuals who were given a combination of opioids and SSRIs. Other research has indicated a small increase in overdose risk for people who are prescribed CYP2D6-inhibiting SSRIs (e.g. fluoxetine and paroxetine) with oxycodone. Overall, risk is low with this combination but, as always, be mindful of your consumption.", + "status": "Low Risk & No Synergy" + }, + "pcp": { + "note": "Details of this combination are not well understood but PCP generally interacts in an unpredictable manner.", + "status": "Unsafe" + }, + "tramadol": { + "status": "Dangerous" + } + }, + "tramadol": { + "2c-t-x": { + "status": "Unsafe" + }, + "2c-x": { + "note": "Tramadol is well known to lower seizure threshold and psychedelics raise the risk of seizures.", + "status": "Unsafe" + }, + "5-meo-xxt": { + "status": "Unsafe" + }, + "alcohol": { + "note": "Heavy CNS depressants, risk of seizures. Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. Place the affected individual in the recovery position to prevent vomit aspiration from excess. Memory blackouts are likely.", + "status": "Dangerous" + }, + "amphetamines": { + "note": "Tramadol and stimulants both increase the risk of seizures.", + "status": "Dangerous" + }, + "amt": { + "status": "Dangerous" + }, + "benzodiazepines": { + "note": "Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present. Vomit aspiration is a risk when passed out, lay down in recovery position if ingested.", + "status": "Dangerous" + }, + "caffeine": { + "status": "Low Risk & No Synergy" + }, + "cannabis": { + "status": "Low Risk & Synergy" + }, + "cocaine": { + "note": "Tramadol and stimulants both increase the risk of seizures.", + "status": "Dangerous" + }, + "dextromethorphan": { + "status": "Dangerous" + }, + "diphenhydramine": { + "note": "Both drugs increase the risk of serotonin syndrome. While at medical dosages, this is unlikely to be of concern, recreational doses should be avoided. Diphenhydramine may increase tramadol’s seizure risk.", + "sources": [ + { + "author": "Benson, B. E., Farooqi, M. F., Klein-Schwartz, W., Litovitz, T., Webb, A. N., Borys, D. J., Lung, D., Rutherfoord Rose, S., Aleguas, A., Sollee, D. R., & Seifert, S. A. (2010)", + "title": "Diphenhydramine dose–response: a novel approach to determine triage thresholds. Clinical Toxicology, 48(8), 820–831.", + "url": "https://doi.org/10.3109/15563650.2010.514269" + }, + { + "author": "Dhesi, M., Maldonado, K. A., Patel, P., & Maani, C. V. (2025)", + "title": "Tramadol. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK537060/" + }, + { + "author": "Hughes, A. R., Lin, A., Hendrickson, R. G., & on behalf of Toxicology Investigator’s Consortium (ToxIC). (2021)", + "title": "Clinical and patient characteristics associated with severe outcome in diphenhydramine toxicity. Clinical Toxicology, 59(10), 918–925.", + "url": "https://doi.org/10.1080/15563650.2021.1891244" + }, + { + "author": "Khan, S., Saud, S., Khan, I., Asif, M., Ismail, O., Salam, A., Yang, T. J., & Norville, K. J. (2018)", + "title": "Serotonin Syndrome Presenting with Concomitant Tramadol and Diphenhydramine Use: A Case Report of an Unlikely Side-Effect. Cureus.", + "url": "https://doi.org/10.7759/cureus.2421" + }, + { + "author": "Kim, H., Kim, S. H., & Kim, J. B. (2021)", + "title": "Antihistamines as a common cause of new-onset seizures: a single-center observational study. Neurological Sciences: Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology, 42(6), 2505–2508.", + "url": "https://doi.org/10.1007/s10072-021-05043-2" + }, + { + "author": "Kim, H., Wang, I.-N., Park, J.-S., Kim, K.-T., Kong, J., Kim, J. B., & Kim, D.-J. (2023)", + "title": "Inherent seizure susceptibility in patients with antihistamine-induced acute symptomatic seizure: a resting-state EEG analysis. Scientific Reports, 13(1), 9146.", + "url": "https://doi.org/10.1038/s41598-023-36415-7" + }, + { + "author": "Sanaei-Zadeh, H. (2012)", + "title": "Diphenhydramine overdose and serotonin syndrome. Psychiatry and Clinical Neurosciences, 66(3), 244–245.", + "url": "https://doi.org/10.1111/j.1440-1819.2012.02320.x" + }, + { + "author": "Sicari, V., Patel, P., & Zabbo, C. P. (2025)", + "title": "Diphenhydramine. In StatPearls. StatPearls Publishing.", + "url": "http://www.ncbi.nlm.nih.gov/books/NBK526010/" + } + ], + "status": "Dangerous" + }, + "dmt": { + "note": "Tramadol is well known to lower seizure threshold and psychedelics also cause occasional seizures.", + "status": "Unsafe" + }, + "dox": { + "note": "Tramadol is well known to lower seizure threshold and psychedelics also cause occasional seizures.", + "status": "Unsafe" + }, + "ghb/gbl": { + "note": "The sedative effects of this combination can lead to dangerous respiratory depression.", + "status": "Dangerous" + }, + "ketamine": { + "status": "Dangerous" + }, + "lithium": { + "note": "Tramadol and Lithium both increase the risk of seizures and serotonin syndrome.", + "sources": [ + { + "author": "Steven C. Julius, Richard P. Brenner", + "title": "Myoclonic seizures with lithium", + "url": "https://doi.org/10.1016/0006-3223(87)90026-6" + }, + { + "author": "Charles DeBattista, Mehmet Sofuoglu, and Alan F. Schatzberg", + "title": "Serotonergic Synergism: The Risks and Benefits of Combining the Selective Serotonin Reuptake Inhibitors with Other Serotonergic Drugs", + "url": "https://doi.org/10.1016/s0006-3223(98)00161-9" + }, + { + "author": "Massot, O., Rousselle, JC., Fillion, MP. et al.", + "title": "5-HT1B Receptors: A Novel Target for Lithium: Possible Involvement in Mood Disorders", + "url": "https://doi.org/10.1016/S0893-133X(99)00042-1" + }, + { + "author": "Sameer Hassamal, Karen Miotto, William Dale, Itai Danovitch ", + "title": "Tramadol: Understanding the Risk of Serotonin Syndrome and Seizures", + "url": "https://doi.org/10.1016/j.amjmed.2018.04.025" + }, + { + "author": "Boostani R, Derakhshan S.", + "title": "Tramadol induced seizure: A 3-year study.", + "url": "https://pubmed.ncbi.nlm.nih.gov/24009919/" + }, + { + "author": "Lagard, C.; Vodovar, D.; Chevillard, L.; Callebert, J.; Caillé, F.; Pottier, G.; Liang, H.; Risède, P.; Tournier, N.; Mégarbane, B.", + "title": "Investigation of the Mechanisms of Tramadol-Induced Seizures in Overdose in the Rat ", + "url": "https://doi.org/10.3390/ph15101254 " + }, + { + "author": "Sansone RA, Sansone LA.", + "title": "Tramadol", + "url": "https://pubmed.ncbi.nlm.nih.gov/19724727" + } + ], + "status": "Dangerous" + }, + "lsd": { + "note": "Tramadol is well known to lower seizure threshold and psychedelics also cause occasional seizures.", + "status": "Unsafe" + }, + "maois": { + "status": "Dangerous" + }, + "mdma": { + "note": "Tramadol and stimulants both increase the risk of seizures.", + "status": "Dangerous" + }, + "mephedrone": { + "note": "There is a high risk of serotonin syndrome and seizures at recreational dosages. Both substances affect the heart and may lead to further dangerous heart complications at higher dosages. Both can dull each other's effects, so if one wears off before the other it's possible to overdose due to the lack of counteraction. The combination may increase each other's side effects, such as dizziness and drowsiness. At higher dosages, the combination may increase each other’s side effects, such as delirium, mania, and psychosis.", + "sources": [ + { + "author": "Boostani, R., & Derakhshan, S.", + "title": "Tramadol induced seizure: A 3-year study. Caspian Journal of Internal Medicine, 3(3), 484–487 (2012)", + "url": "N/A" + }, + { + "author": "Ener, R. A., Meglathery, S. B., Decker, W. A. V., & Gallagher, R. M.", + "title": "Serotonin Syndrome and Other Serotonergic Disorders: Table 1. Pain Medicine, 4(1), 63–74 (2003)", + "url": "https://doi.org/10.1046/j.1526-4637.2003.03005.x" + }, + { + "author": "Hadlock, G. C., Webb, K. M., McFadden, L. M., Chu, P. W., Ellis, J. D., Allen, S. C., Andrenyak, D. M., Vieira-Brock, P. L., German, C. L., Conrad, K. M., Hoonakker, A. J., Gibb, J. W., Wilkins, D. G., Hanson, G. R., & Fleckenstein, A. E.", + "title": "4-Methylmethcathinone (Mephedrone): Neuropharmacological Effects of a Designer Stimulant of Abuse. The Journal of Pharmacology and Experimental Therapeutics, 339(2), 530–536 (2011)", + "url": "https://doi.org/10.1124/jpet.111.184119" + }, + { + "author": "Kehr, J., Ichinose, F., Yoshitake, S., Goiny, M., Sievertsson, T., Nyberg, F., & Yoshitake, T.", + "title": "Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats: Mephedrone increases both DA and 5-HT in rat brain. British Journal of Pharmacology, 164(8), 1949–1958 (2011)", + "url": "https://doi.org/10.1111/j.1476-5381.2011.01499.x" + }, + { + "author": "Lagard, C., Vodovar, D., Chevillard, L., Callebert, J., Caillé, F., Pottier, G., Liang, H., Risède, P., Tournier, N., & Mégarbane, B.", + "title": "Investigation of the Mechanisms of Tramadol-Induced Seizures in Overdose in the Rat. Pharmaceuticals, 15(10), 1254 (2022)", + "url": "https://doi.org/10.3390/ph15101254" + }, + { + "author": "Meng, H., Cao, J., Kang, J., Ying, X., Ji, J., Reynolds, W., & Rampe, D.", + "title": "Mephedrone, a new designer drug of abuse, produces acute hemodynamic effects in the rat. Toxicology Letters, 208(1), 62–68 (2012)", + "url": "https://doi.org/10.1016/j.toxlet.2011.10.010" + }, + { + "author": "Sansone, R. A., & Sansone, L. A.", + "title": "Tramadol: seizures, serotonin syndrome, and coadministered antidepressants. Psychiatry (Edgmont (Pa.: Township)), 6(4), 17–21 (2009)", + "url": "N/A" + } + ], + "status": "Dangerous" + }, + "mescaline": { + "note": "This combination can cause seizures due to the lowering of the threshold by tramadol and the potential of mescaline to cause seziures.", + "status": "Unsafe" + }, + "mushrooms": { + "note": "Tramadol is well known to lower seizure threshold and psychedelics also cause occasional seizures.", + "status": "Unsafe" + }, + "mxe": { + "status": "Dangerous" + }, + "nbomes": { + "note": "Tramadol is well known to lower seizure threshold and NBOMes have also shown a tendency to cause severe seizures", + "status": "Unsafe" + }, + "nitrous": { + "note": "Both substances potentiate the ataxia and sedation caused by the other and can lead to unexpected loss of consciousness at high doses. While unconscious, vomit aspiration is a risk if not placed in the recovery position. Memory blackouts are likely.", + "status": "Caution" + }, + "opioids": { + "note": "Concomitant use of tramadol increases the seizure risk in individuals taking other opioids. These agents are often individually epileptogenic and may have additive effects on seizure threshold during coadministration. Central nervous system- and/or respiratory-depressant effects may be additively or synergistically present", + "status": "Dangerous" + }, + "pcp": { + "status": "Dangerous" + }, + "pregabalin": { + "note": "There is a significant risk of seizures. Both substances are CNS depressants, potentiating each other strongly and unpredictably, raising the chances of memory loss, severe ataxia, and unconsciousness. The interaction will cause greater inhibition and risk of injury. If the user falls unconscious it is strongly recommended to put them into the recovery position and monitor breathing. Medical dosages are not reported to be a concern.", + "sources": [ + { + "author": "Altair. (n.d.-a)", + "title": "Pregabalin (Lyrica) - Erowid Exp - “Heart Arrhythmia, Seizure : Not Recreational.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=69917" + }, + { + "author": "Ben-Menachem, E. (2004)", + "title": "Pregabalin pharmacology and its relevance to clinical practice. Epilepsia, 45 Suppl 6, 13–18.", + "url": "https://doi.org/10.1111/j.0013-9580.2004.455003.x" + }, + { + "author": "Boostani, R., & Derakhshan, S. (2012)", + "title": "Tramadol induced seizure: A 3-year study. Caspian Journal of Internal Medicine, 3(3), 484–487.", + "url": "https://pubmed.ncbi.nlm.nih.gov/24009919/" + }, + { + "author": "Douke, R. (n.d.)", + "title": "Pregabalin & Tramadol - Erowid Exp - “Grand Mal Seizures.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=83232" + }, + { + "author": "French, J., Kwan, P., Fakhoury, T., Pitman, V., DuBrava, S., Knapp, L., & Yurkewicz, L. (2014)", + "title": "Pregabalin monotherapy in patients with partial-onset seizures. Neurology, 82(7), 590–597.", + "url": "https://doi.org/10.1212/WNL.0000000000000119" + }, + { + "author": "Hassamal, S., Miotto, K., Dale, W., & Danovitch, I. (2018)", + "title": "Tramadol: Understanding the Risk of Serotonin Syndrome and Seizures. The American Journal of Medicine, 131(11), 1382.e1-1382.e6.", + "url": "https://doi.org/10.1016/j.amjmed.2018.04.025" + }, + { + "author": "Lyndon, A., Audrey, S., Wells, C., Burnell, E. S., Ingle, S., Hill, R., Hickman, M., & Henderson, G. (2017)", + "title": "Risk to heroin users of polydrug use of pregabalin or gabapentin: Risks in combining gabapentoids with heroin. Addiction, 112(9), 1580–1589.", + "url": "https://doi.org/10.1111/add.13843" + }, + { + "author": "Rietjens, S. J., Sikma, M. A., Hunault, C. C., De Lange, D. W., & Hondebrink, L. (2022)", + "title": "Pregabalin poisoning: Evaluation of dose‐toxicity relationship. British Journal of Clinical Pharmacology, 88(3), 1288–1297.", + "url": "https://doi.org/10.1111/bcp.15073" + }, + { + "author": "Sean. (n.d.-b)", + "title": "Pregabalin - Erowid Exp - “Stay Away.”", + "url": "https://www.erowid.org/experiences/exp.php?ID=67302" + }, + { + "author": "Slocum, G. W., Schult, R. F., Gorodetsky, R. M., Wiegand, T. J., Kamali, M., & Acquisto, N. M. (2018)", + "title": "Pregabalin and paradoxical reaction of seizures in a large overdose. Toxicology Communications, 2(1), 19–20.", + "url": "https://doi.org/10.1080/24734306.2018.1458465" + } + ], + "status": "Unsafe" + }, + "ssris": { + "status": "Dangerous" + } + } +} \ No newline at end of file diff --git a/src/pages/combos.tsx b/src/pages/combos.tsx new file mode 100644 index 0000000..ff37935 --- /dev/null +++ b/src/pages/combos.tsx @@ -0,0 +1,21 @@ +import React from 'react'; +import Head from 'next/head'; +// Note: We are importing from components, NOT components/src +import DrugInteractionChecker from '../components/DrugInteractionChecker'; + +export default function CombosPage() { + return ( + <> + + Interaction Checker | TripSit + + + + + {/* The component handles its own dark background/theme */} +
+ +
+ + ); +}