{
 "name": "Psilocybin medication and substance interaction evidence summary",
 "description": "26 medication and substance classes with what published research says about combining them with psilocybin, the type of evidence, the direction of the effect, and primary sources with PubMed IDs.",
 "publisher": "Magic Mushroom Dosage Calculator",
 "url": "https://magicmushroomdosagecalculator.com/psilocybin-interactions",
 "license": "CC BY 4.0",
 "license_url": "https://creativecommons.org/licenses/by/4.0/",
 "updated": "2026-10-26",
 "record_count": 26,
 "source_note": "A summary of published evidence, not medical advice. Talk to a prescriber or pharmacist; do not stop prescribed medicines abruptly.",
 "records": [
  {
   "id": "lithium",
   "class": "Lithium",
   "examples": [
    "lithium carbonate",
    "lithium citrate"
   ],
   "summary": "In 62 online reports of lithium taken with a classic psychedelic (such as LSD or psilocybin), 47% described seizures and 39% involved medical attention, while none of 34 lamotrigine reports described seizures (Nayak 2021). A 2024 case report described three seizures after LSD in a teenager recently started on low-dose lithium, and a 2024 scoping review concluded lithium could increase seizure risk with psychedelics. Older LSD reports (n = 3) described stronger and faster effects on chronic lithium.",
   "evidence_level": "observational or survey (online experience reports) plus case reports",
   "direction": "serious",
   "what_it_means": "This is the strongest warning among the medicines in this checker: seizures. If you take lithium, talk to your prescriber or pharmacist before any decision involving psilocybin. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Nayak et al. 2021. Classic psychedelic coadministration with lithium, but not lamotrigine, is associated with seizures. Pharmacopsychiatry 54(5):240-245",
     "url": "https://pubmed.ncbi.nlm.nih.gov/34348413/",
     "pmid": "34348413"
    },
    {
     "title": "Edwards et al. 2024. New-onset seizures in an adolescent following use of LSD while on low-dose lithium therapy: a case study. S D Med",
     "url": "https://pubmed.ncbi.nlm.nih.gov/38986146/",
     "pmid": "38986146"
    },
    {
     "title": "Soto-Angona et al. 2024. Do classic psychedelics increase the risk of seizures? A scoping review. Eur Neuropsychopharmacol",
     "url": "https://pubmed.ncbi.nlm.nih.gov/38917636/",
     "pmid": "38917636"
    },
    {
     "title": "Bonson and Murphy 1996. Alterations in responses to LSD in humans associated with chronic administration of tricyclic antidepressants, MAOIs or lithium. Behav Brain Res",
     "url": "https://pubmed.ncbi.nlm.nih.gov/8788508/",
     "pmid": "8788508"
    },
    {
     "title": "Johnson, Richards, Griffiths 2008. Human hallucinogen research: guidelines for safety. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3056407/",
     "pmid": "18593734"
    },
    {
     "title": "Lithium carbonate prescribing information (serotonin syndrome warning)",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=01c4facd-ed79-4078-ba33-2044de372d0f",
     "pmid": null
    }
   ]
  },
  {
   "id": "ssri",
   "class": "SSRIs (selective serotonin reuptake inhibitors)",
   "examples": [
    "sertraline",
    "escitalopram",
    "citalopram",
    "fluoxetine",
    "paroxetine",
    "fluvoxamine",
    "vilazodone",
    "vortioxetine"
   ],
   "summary": "In an online survey, weaker-than-expected mushroom effects were reported with SSRIs in 47% of cases (95% CI 41-54%; n = 611 reports across antidepressants), and reduced effects persisted at about 30% for up to 3 to 6 months after stopping (Gukasyan 2023). In a controlled crossover study of 23 healthy people, 14 days of escitalopram did not reduce positive effects but reduced anxiety, bad drug effects and blood pressure rises (Becker 2022). In 19 patients kept on SSRIs, 2 had severe blood pressure rises treated with clonidine and none had serious adverse events (Goodwin 2023). Reviews rate serotonin toxicity risk as low when no MAOI is involved (Malcolm and Thomas 2022).",
   "evidence_level": "controlled study (small) plus observational or survey",
   "direction": "changes",
   "what_it_means": "SSRIs often weaken the experience, and this can persist for months after stopping. Talk to your prescriber or pharmacist; do not stop an SSRI to make room for psilocybin. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Gukasyan et al. 2023. Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use. J Psychopharmacol",
     "url": "https://pubmed.ncbi.nlm.nih.gov/37291890/",
     "pmid": "37291890"
    },
    {
     "title": "Becker et al. 2022. Acute effects of psilocybin after escitalopram or placebo pretreatment: randomized, double-blind, placebo-controlled crossover study. Clin Pharmacol Ther",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9299061/",
     "pmid": "34743319"
    },
    {
     "title": "Goodwin et al. 2023. Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication. Neuropsychopharmacology",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10425429/",
     "pmid": "37443386"
    },
    {
     "title": "Bonson et al. 1996. Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans. Neuropsychopharmacology",
     "url": "https://pubmed.ncbi.nlm.nih.gov/8726753/",
     "pmid": "8726753"
    },
    {
     "title": "Malcolm and Thomas 2022. Serotonin toxicity of serotonergic psychedelics. Psychopharmacology",
     "url": "https://pubmed.ncbi.nlm.nih.gov/34251464/",
     "pmid": "34251464"
    },
    {
     "title": "Do et al. 2024. Serotoninergic antidepressants combination in psilocybin-assisted psychotherapy: a case report. Front Psychiatry",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11289768/",
     "pmid": "39086732"
    },
    {
     "title": "Prozac (fluoxetine) prescribing information: elimination half-life",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c88f33ed-6dfb-4c5e-bc01-d8e36dd97299",
     "pmid": null
    }
   ]
  },
  {
   "id": "snri",
   "class": "SNRIs (serotonin-norepinephrine reuptake inhibitors)",
   "examples": [
    "venlafaxine",
    "desvenlafaxine",
    "duloxetine",
    "levomilnacipran",
    "milnacipran"
   ],
   "summary": "Weaker-than-expected effects were reported with SNRIs in 55% of survey cases (95% CI 44-67%) (Gukasyan 2023). No controlled study of psilocybin with an SNRI was found; one case report describes psilocybin-assisted therapy given with duloxetine plus vortioxetine without cardiovascular concerns. Venlafaxine and desvenlafaxine are among the antidepressants most associated with frequent and severe discontinuation symptoms (Henssler 2024).",
   "evidence_level": "observational or survey",
   "direction": "changes",
   "what_it_means": "Likely to weaken effects, and these medicines are among the hardest to stop. Talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Gukasyan et al. 2023. Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use. J Psychopharmacol",
     "url": "https://pubmed.ncbi.nlm.nih.gov/37291890/",
     "pmid": "37291890"
    },
    {
     "title": "Do et al. 2024. Serotoninergic antidepressants combination in psilocybin-assisted psychotherapy: a case report. Front Psychiatry",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11289768/",
     "pmid": "39086732"
    },
    {
     "title": "Henssler et al. 2024. Incidence of antidepressant discontinuation symptoms: systematic review and meta-analysis. Lancet Psychiatry",
     "url": "https://pubmed.ncbi.nlm.nih.gov/38851198/",
     "pmid": "38851198"
    },
    {
     "title": "Malcolm and Thomas 2022. Serotonin toxicity of serotonergic psychedelics. Psychopharmacology",
     "url": "https://pubmed.ncbi.nlm.nih.gov/34251464/",
     "pmid": "34251464"
    }
   ]
  },
  {
   "id": "stopping-medication",
   "class": "Stopping prescribed medication (antidepressant discontinuation)",
   "examples": [
    "any antidepressant",
    "benzodiazepines",
    "lamotrigine and other anticonvulsants",
    "beta-blockers",
    "clonidine"
   ],
   "summary": "A 2024 meta-analysis (79 studies, 21,002 patients) found discontinuation symptoms in 31% after stopping antidepressants vs 17% after placebo, with severe symptoms in 2.8% vs 0.6%; a 2025 reanalysis of 5 systematically measured studies estimated 55% (95% CI 31-81%). Labels warn that abrupt stopping can cause seizures (lamotrigine, benzodiazepines), angina or heart attack (beta-blockers) and rebound high blood pressure (clonidine). Trials tapered antidepressants under weekly supervision with suicidality checks, and post hoc analyses disagree on whether stopping helps psilocybin work (Erritzoe 2024 vs Marwood 2024).",
   "evidence_level": "controlled study (meta-analysis of trials) plus drug labels",
   "direction": "serious",
   "what_it_means": "Stopping a prescribed medicine is itself a medical decision with real risks. Any change belongs with your prescriber or pharmacist; never stop abruptly.",
   "sources": [
    {
     "title": "Henssler et al. 2024. Incidence of antidepressant discontinuation symptoms: systematic review and meta-analysis. Lancet Psychiatry",
     "url": "https://pubmed.ncbi.nlm.nih.gov/38851198/",
     "pmid": "38851198"
    },
    {
     "title": "Moncrieff et al. 2025. Evidence on antidepressant withdrawal: appraisal and reanalysis of a recent systematic review. Psychol Med",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC12315658/",
     "pmid": "40692314"
    },
    {
     "title": "Erritzoe et al. 2024. Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11102650/",
     "pmid": "38520045"
    },
    {
     "title": "Marwood et al. 2024. The impact of antidepressant discontinuation prior to treatment with psilocybin for treatment-resistant depression. J Psychiatr Res",
     "url": "https://pubmed.ncbi.nlm.nih.gov/39427449/",
     "pmid": "39427449"
    },
    {
     "title": "Zoloft (sertraline) prescribing information: discontinuation syndrome",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fda754f6-d0f3-4dce-a17a-927d64f912f7",
     "pmid": null
    },
    {
     "title": "Lamictal XR (lamotrigine) prescribing information: withdrawal seizures",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3e2c9a35-6a39-41d7-ad84-3c0bb8894b09",
     "pmid": null
    },
    {
     "title": "Xanax (alprazolam) prescribing information: dependence and withdrawal reactions",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=388e249d-b9b6-44c3-9f8f-880eced0239f",
     "pmid": null
    },
    {
     "title": "Toprol-XL (metoprolol) prescribing information: abrupt cessation",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=496ddfaa-7c9c-4888-b747-a210249b367a",
     "pmid": null
    },
    {
     "title": "Catapres-TTS (clonidine) prescribing information: withdrawal",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=39e1d35e-533c-4647-8649-8168a6e92dfa",
     "pmid": null
    },
    {
     "title": "COMPASS COMP001 protocol v4.0 (NCT03775200)",
     "url": "https://cdn.clinicaltrials.gov/large-docs/00/NCT03775200/Prot_000.pdf",
     "pmid": null
    }
   ]
  },
  {
   "id": "maoi",
   "class": "MAOIs (monoamine oxidase inhibitors, prescription)",
   "examples": [
    "phenelzine",
    "tranylcypromine",
    "isocarboxazid",
    "selegiline",
    "rasagiline",
    "moclobemide",
    "linezolid"
   ],
   "summary": "A 2025 case report described a hypertensive emergency with ST-elevation about half an hour after psilocybin mushrooms in a man taking tranylcypromine plus extended-release amphetamine; the authors suspect phenylethylamine in the mushrooms. A 2026 review lists hypertensive urgency or emergency with MAOIs plus psilocybin mushrooms among reported events. Serotonin toxicity reviews place the main risk on combinations involving MAOIs. In older LSD reports, phenelzine nearly abolished LSD effects (n = 2). MAO-A breaks down part of the psilocin, but glucuronidation is likely the main route.",
   "evidence_level": "case reports plus pharmacological theory",
   "direction": "serious",
   "what_it_means": "MAOIs have many dangerous interactions, and a published case links an MAOI plus a stimulant plus psilocybin mushrooms with a hypertensive emergency. Talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Barnett et al. 2025. Hypertensive emergency secondary to combining psilocybin mushrooms, extended release dextroamphetamine-amphetamine, and tranylcypromine. J Psychoactive Drugs",
     "url": "https://pubmed.ncbi.nlm.nih.gov/38903003/",
     "pmid": "38903003"
    },
    {
     "title": "Rached et al. 2026. Safety and efficacy of MAOIs in patients who use psychoactive substances. CNS Drugs",
     "url": "https://pubmed.ncbi.nlm.nih.gov/41546846/",
     "pmid": "41546846"
    },
    {
     "title": "Malcolm and Thomas 2022. Serotonin toxicity of serotonergic psychedelics. Psychopharmacology",
     "url": "https://pubmed.ncbi.nlm.nih.gov/34251464/",
     "pmid": "34251464"
    },
    {
     "title": "Bonson and Murphy 1996. Alterations in responses to LSD in humans associated with chronic administration of tricyclic antidepressants, MAOIs or lithium. Behav Brain Res",
     "url": "https://pubmed.ncbi.nlm.nih.gov/8788508/",
     "pmid": "8788508"
    },
    {
     "title": "Thomann et al. 2024. In vitro and in vivo metabolism of psilocybin's active metabolite psilocin. Front Pharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11089204/",
     "pmid": "38741590"
    },
    {
     "title": "Sacher et al. 2011. MAO-A inhibitor occupancy during treatment with moclobemide or St John's wort: [11C]-harmine PET study. J Psychiatry Neurosci",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3201991/",
     "pmid": "21463543"
    },
    {
     "title": "Nardil (phenelzine) prescribing information",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=513a41d0-37d4-4355-8a6d-a2c643bce6fa",
     "pmid": null
    },
    {
     "title": "Parnate (tranylcypromine) prescribing information",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b72d8187-dfcc-4ea0-b5e9-c0be95b69a27",
     "pmid": null
    },
    {
     "title": "Emsam (selegiline transdermal) prescribing information",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b891bd9f-fdb8-4862-89c5-ecdd700398a3",
     "pmid": null
    }
   ]
  },
  {
   "id": "harmala-ayahuasca",
   "class": "Harmala alkaloids and ayahuasca (beta-carboline MAO-A inhibitors)",
   "examples": [
    "harmine",
    "harmaline",
    "tetrahydroharmine",
    "Syrian rue (Peganum harmala)",
    "ayahuasca vine (Banisteriopsis caapi)"
   ],
   "summary": "Beta-carbolines inhibit MAO-A and are what make DMT in ayahuasca orally active. Case reports describe serotonin-toxicity-like reactions when ayahuasca or harmala extracts met fluoxetine, and severe reactions and a death with harmala alkaloids plus 5-MeO-DMT. No human study or case report of psilocybin combined with harmala alkaloids was found. Psilocybe mushrooms themselves contain small amounts of beta-carbolines such as harmane and harmine (Blei 2020).",
   "evidence_level": "case reports (with other tryptamines) plus pharmacological theory",
   "direction": "serious",
   "what_it_means": "Harmala products add MAO inhibition, and serious reactions have been reported when they meet antidepressants or other tryptamines. If you take prescribed medicines, talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Halman et al. 2024. Drug-drug interactions involving classic psychedelics: a systematic review. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10851641/",
     "pmid": "37982394"
    },
    {
     "title": "Blei et al. 2020. Simultaneous production of psilocybin and a cocktail of beta-carboline MAO inhibitors in magic mushrooms. Chemistry",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7003923/",
     "pmid": "31729089"
    },
    {
     "title": "Malcolm and Thomas 2022. Serotonin toxicity of serotonergic psychedelics. Psychopharmacology",
     "url": "https://pubmed.ncbi.nlm.nih.gov/34251464/",
     "pmid": "34251464"
    },
    {
     "title": "Rached et al. 2026. Safety and efficacy of MAOIs in patients who use psychoactive substances. CNS Drugs",
     "url": "https://pubmed.ncbi.nlm.nih.gov/41546846/",
     "pmid": "41546846"
    }
   ]
  },
  {
   "id": "tricyclic",
   "class": "Tricyclic antidepressants (TCAs)",
   "examples": [
    "amitriptyline",
    "nortriptyline",
    "imipramine",
    "desipramine",
    "clomipramine",
    "doxepin"
   ],
   "summary": "In 1996 retrospective reports, people on chronic imipramine (n = 2), desipramine (n = 2) or clomipramine (n = 1) described earlier onset and stronger LSD effects; no psilocybin-specific data were found. Hopkins safety guidelines treat chronic TCAs as potentiating hallucinogen effects and a safety concern. TCAs carry their own seizure and heart-rhythm risks: the clomipramine label calls seizure its most significant risk.",
   "evidence_level": "case reports (LSD) plus pharmacological theory",
   "direction": "serious",
   "what_it_means": "Unlike SSRIs, TCAs may intensify psychedelic effects, and they affect seizure threshold and heart rhythm. Talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Bonson and Murphy 1996. Alterations in responses to LSD in humans associated with chronic administration of tricyclic antidepressants, MAOIs or lithium. Behav Brain Res",
     "url": "https://pubmed.ncbi.nlm.nih.gov/8788508/",
     "pmid": "8788508"
    },
    {
     "title": "Halman et al. 2024. Drug-drug interactions involving classic psychedelics: a systematic review. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10851641/",
     "pmid": "37982394"
    },
    {
     "title": "Johnson, Richards, Griffiths 2008. Human hallucinogen research: guidelines for safety. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3056407/",
     "pmid": "18593734"
    },
    {
     "title": "Anafranil (clomipramine) prescribing information: seizures",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4074b555-7635-41a9-809d-fae3b3610059",
     "pmid": null
    },
    {
     "title": "Henssler et al. 2024. Incidence of antidepressant discontinuation symptoms: systematic review and meta-analysis. Lancet Psychiatry",
     "url": "https://pubmed.ncbi.nlm.nih.gov/38851198/",
     "pmid": "38851198"
    }
   ]
  },
  {
   "id": "trazodone",
   "class": "Trazodone",
   "examples": [
    "trazodone"
   ],
   "summary": "Trazodone blocks 5-HT2A receptors (the main psilocybin target) and inhibits serotonin reuptake. One 1996 case reported reduced LSD effects on trazodone; no psilocybin data were found. Its label warns of serotonin syndrome and QT prolongation. Usona's phase 2 trial required stopping trazodone used for sleep 2 weeks before baseline.",
   "evidence_level": "case reports (LSD) plus pharmacological theory",
   "direction": "changes",
   "what_it_means": "Expected to weaken effects. Talk to your prescriber or pharmacist before changing any sleep or antidepressant medicine. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Halman et al. 2024. Drug-drug interactions involving classic psychedelics: a systematic review. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10851641/",
     "pmid": "37982394"
    },
    {
     "title": "Bonson et al. 1996. Chronic administration of serotonergic antidepressants attenuates the subjective effects of LSD in humans. Neuropsychopharmacology",
     "url": "https://pubmed.ncbi.nlm.nih.gov/8726753/",
     "pmid": "8726753"
    },
    {
     "title": "Trazodone prescribing information: serotonin syndrome, QT",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=007f38e0-653b-43e4-a1c1-b59997b2762a",
     "pmid": null
    },
    {
     "title": "Usona PSIL201 protocol v10.0 (NCT03866174), exclusion criteria",
     "url": "https://cdn.clinicaltrials.gov/large-docs/74/NCT03866174/Prot_000.pdf",
     "pmid": null
    }
   ]
  },
  {
   "id": "mirtazapine",
   "class": "Mirtazapine",
   "examples": [
    "mirtazapine",
    "mianserin"
   ],
   "summary": "Mirtazapine blocks 5-HT2A receptors, and a 2024 systematic review lists it among medicines expected to diminish psychedelic effects. No human psilocybin data were found. Its label lists serotonin syndrome and QT prolongation risks.",
   "evidence_level": "pharmacological theory",
   "direction": "changes",
   "what_it_means": "Likely to dampen effects; no safety data for the combination. Talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Halman et al. 2024. Drug-drug interactions involving classic psychedelics: a systematic review. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10851641/",
     "pmid": "37982394"
    },
    {
     "title": "Remeron (mirtazapine) prescribing information",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=98ad1917-a094-44f5-a28f-a64a8cfcd887",
     "pmid": null
    }
   ]
  },
  {
   "id": "bupropion",
   "class": "Bupropion",
   "examples": [
    "bupropion"
   ],
   "summary": "In the 2023 survey, weaker-than-expected effects were reported less often with bupropion (29%; 95% CI 20-39%) than with SSRIs (47%) or SNRIs (55%). Bupropion's label warns of dose-related seizure risk and raised blood pressure. No case of seizure from psilocybin plus bupropion was found; in one LSD case, seizures appeared only after lithium was added to fluoxetine plus bupropion.",
   "evidence_level": "observational or survey plus pharmacological theory",
   "direction": "unclear",
   "what_it_means": "Less dampening than SSRIs in one survey, but bupropion lowers the seizure threshold and can raise blood pressure on its own. Talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Gukasyan et al. 2023. Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use. J Psychopharmacol",
     "url": "https://pubmed.ncbi.nlm.nih.gov/37291890/",
     "pmid": "37291890"
    },
    {
     "title": "Wellbutrin XL (bupropion) prescribing information: seizure risk, hypertension",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a435da9d-f6e8-4ddc-897d-8cd2bf777b21",
     "pmid": null
    },
    {
     "title": "Edwards et al. 2024. New-onset seizures in an adolescent following use of LSD while on low-dose lithium therapy: a case study. S D Med",
     "url": "https://pubmed.ncbi.nlm.nih.gov/38986146/",
     "pmid": "38986146"
    }
   ]
  },
  {
   "id": "buspirone",
   "class": "Buspirone",
   "examples": [
    "buspirone"
   ],
   "summary": "In a double-blind within-subject study (n = 19 healthy), buspirone significantly reduced psilocybin-induced visual effects (Visionary Restructuralization, p < 0.001), with a trend reduction in oceanic boundlessness (p = 0.062). Its label contraindicates use with MAOIs because of serotonin syndrome and raised blood pressure.",
   "evidence_level": "controlled study",
   "direction": "changes",
   "what_it_means": "Shown to reduce visual effects in a controlled study. Talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Pokorny et al. 2016. Modulatory effect of the 5-HT1A agonist buspirone and ergotamine on psilocybin-induced psychedelic experience. Eur Neuropsychopharmacol",
     "url": "https://pubmed.ncbi.nlm.nih.gov/26875114/",
     "pmid": "26875114"
    },
    {
     "title": "Halman et al. 2024. Drug-drug interactions involving classic psychedelics: a systematic review. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10851641/",
     "pmid": "37982394"
    },
    {
     "title": "Buspirone prescribing information: MAOI contraindication",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=02628a0c-bfdb-4a58-8e48-bcd8ca12d53b",
     "pmid": null
    }
   ]
  },
  {
   "id": "antipsychotics",
   "class": "Antipsychotics and 5-HT2A blockers",
   "examples": [
    "risperidone",
    "olanzapine",
    "quetiapine",
    "aripiprazole",
    "haloperidol",
    "chlorpromazine",
    "ketanserin (research only)"
   ],
   "summary": "In controlled studies in healthy volunteers, risperidone and the research drug ketanserin blocked psilocybin's effects in a dose-dependent way, while haloperidol increased anxiety and psychosis-like effects without reducing visual effects (Vollenweider 1998). Chlorpromazine reduced visual distortion in a 1967 study (n = 8). Hopkins guidelines advise against haloperidol as rescue medication. People prescribed antipsychotics usually have conditions (psychosis, bipolar disorder) that trials exclude.",
   "evidence_level": "controlled study",
   "direction": "changes",
   "what_it_means": "Most antipsychotics blunt psilocybin, and the conditions they treat are the main reason trials exclude people. Talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Vollenweider et al. 1998. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport",
     "url": "https://pubmed.ncbi.nlm.nih.gov/9875725/",
     "pmid": "9875725"
    },
    {
     "title": "Halman et al. 2024. Drug-drug interactions involving classic psychedelics: a systematic review. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10851641/",
     "pmid": "37982394"
    },
    {
     "title": "Johnson, Richards, Griffiths 2008. Human hallucinogen research: guidelines for safety. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3056407/",
     "pmid": "18593734"
    },
    {
     "title": "Imperial psilocybin vs escitalopram protocol v7 (NCT03429075)",
     "url": "https://cdn.clinicaltrials.gov/large-docs/75/NCT03429075/Prot_000.pdf",
     "pmid": null
    },
    {
     "title": "COMPASS COMP001 protocol v4.0 (NCT03775200)",
     "url": "https://cdn.clinicaltrials.gov/large-docs/00/NCT03775200/Prot_000.pdf",
     "pmid": null
    }
   ]
  },
  {
   "id": "benzodiazepines",
   "class": "Benzodiazepines",
   "examples": [
    "lorazepam",
    "diazepam",
    "alprazolam",
    "clonazepam",
    "midazolam"
   ],
   "summary": "Clinical guidelines and trial protocols name benzodiazepines as the rescue medication of choice when severe anxiety does not respond to reassurance, and a 2026 emergency case report describes their use with supportive care. Some trials allowed stable prescribed benzodiazepines. In a small controlled study (n = 8), midazolam allowed a conscious psychedelic experience while partly impairing memory of it. Benzodiazepine labels warn that abrupt discontinuation can cause withdrawal reactions including seizures.",
   "evidence_level": "controlled study (small) plus clinical guidance and case reports",
   "direction": "changes",
   "what_it_means": "These are what clinicians use to calm severe reactions in emergencies; that is a medical decision, not self-treatment. Talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Johnson, Richards, Griffiths 2008. Human hallucinogen research: guidelines for safety. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3056407/",
     "pmid": "18593734"
    },
    {
     "title": "COMPASS COMP001 protocol v4.0 (NCT03775200)",
     "url": "https://cdn.clinicaltrials.gov/large-docs/00/NCT03775200/Prot_000.pdf",
     "pmid": null
    },
    {
     "title": "Usona PSIL201 protocol v10.0 (NCT03866174), exclusion criteria",
     "url": "https://cdn.clinicaltrials.gov/large-docs/74/NCT03866174/Prot_000.pdf",
     "pmid": null
    },
    {
     "title": "Nicholas et al. 2024. Co-administration of midazolam and psilocybin: differential effects on subjective quality versus memory of the psychedelic experience. Transl Psychiatry",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11393325/",
     "pmid": "39266503"
    },
    {
     "title": "Udoro et al. 2026. Acute hallucinogen intoxication following ingestion of a commercially available mushroom extract product: a case report. Cureus",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13362164/",
     "pmid": "42445624"
    },
    {
     "title": "Xanax (alprazolam) prescribing information: dependence and withdrawal reactions",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=388e249d-b9b6-44c3-9f8f-880eced0239f",
     "pmid": null
    }
   ]
  },
  {
   "id": "tramadol-seizure-threshold",
   "class": "Tramadol and other seizure-threshold-lowering drugs",
   "examples": [
    "tramadol",
    "bupropion",
    "clomipramine and other TCAs",
    "lithium"
   ],
   "summary": "No study or case of psilocybin plus tramadol was found. Tramadol's label warns of potentially life-threatening serotonin syndrome with serotonergic drugs and of seizure risk that rises with SSRIs, SNRIs, TCAs, MAOIs, neuroleptics and other drugs that lower seizure threshold. A 2024 scoping review concluded that psychedelics may not raise seizure risk in healthy people taking no other drugs, but that other substances such as lithium or kambo could.",
   "evidence_level": "pharmacological theory",
   "direction": "serious",
   "what_it_means": "The concern is stacking several drugs that lower the seizure threshold or raise serotonin. Talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Tramadol ER prescribing information: serotonin syndrome, seizure risk",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=004de5a4-80f8-4040-a6ea-be5e99352a36",
     "pmid": null
    },
    {
     "title": "Soto-Angona et al. 2024. Do classic psychedelics increase the risk of seizures? A scoping review. Eur Neuropsychopharmacol",
     "url": "https://pubmed.ncbi.nlm.nih.gov/38917636/",
     "pmid": "38917636"
    },
    {
     "title": "Rached et al. 2026. Safety and efficacy of MAOIs in patients who use psychoactive substances. CNS Drugs",
     "url": "https://pubmed.ncbi.nlm.nih.gov/41546846/",
     "pmid": "41546846"
    },
    {
     "title": "Wellbutrin XL (bupropion) prescribing information: seizure risk, hypertension",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a435da9d-f6e8-4ddc-897d-8cd2bf777b21",
     "pmid": null
    }
   ]
  },
  {
   "id": "stimulants-adhd",
   "class": "Stimulants and ADHD medications",
   "examples": [
    "amphetamine salts",
    "lisdexamfetamine",
    "methylphenidate",
    "dexmethylphenidate",
    "atomoxetine"
   ],
   "summary": "Psilocybin raises blood pressure in trials, and stimulant labels warn of raised blood pressure and heart rate and risks in heart disease. A 2025 case report described a hypertensive emergency when psilocybin mushrooms were taken with extended-release amphetamine and the MAOI tranylcypromine. No controlled study of psilocybin with a stimulant was found. Usona's trial required stopping prescribed stimulants 2 weeks before baseline, and COMP001 excluded methylphenidate.",
   "evidence_level": "case reports plus pharmacological theory",
   "direction": "serious",
   "what_it_means": "Both raise blood pressure and heart rate, and the risk is highest with an MAOI also involved. Talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Barnett et al. 2025. Hypertensive emergency secondary to combining psilocybin mushrooms, extended release dextroamphetamine-amphetamine, and tranylcypromine. J Psychoactive Drugs",
     "url": "https://pubmed.ncbi.nlm.nih.gov/38903003/",
     "pmid": "38903003"
    },
    {
     "title": "Adderall XR prescribing information: blood pressure and heart rate",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aff45863-ffe1-4d4f-8acf-c7081512a6c0",
     "pmid": null
    },
    {
     "title": "Usona PSIL201 protocol v10.0 (NCT03866174), exclusion criteria",
     "url": "https://cdn.clinicaltrials.gov/large-docs/74/NCT03866174/Prot_000.pdf",
     "pmid": null
    },
    {
     "title": "COMPASS COMP001 protocol v4.0 (NCT03775200)",
     "url": "https://cdn.clinicaltrials.gov/large-docs/00/NCT03775200/Prot_000.pdf",
     "pmid": null
    }
   ]
  },
  {
   "id": "blood-pressure-medications",
   "class": "Blood pressure and heart medications",
   "examples": [
    "lisinopril",
    "losartan",
    "amlodipine",
    "metoprolol",
    "clonidine",
    "hydrochlorothiazide"
   ],
   "summary": "No interaction study between psilocybin and blood pressure medicines was found. The main issue is the underlying condition: psilocybin raised systolic pressure above 160 mmHg in 34% of high-dose trial sessions, and trials exclude uncontrolled hypertension and many heart conditions. Clonidine was used to treat severe blood pressure rises in one psilocybin trial. Labels warn that stopping beta-blockers abruptly can trigger angina or heart attack and stopping clonidine abruptly can cause a rapid rise in blood pressure.",
   "evidence_level": "pharmacological theory",
   "direction": "unclear",
   "what_it_means": "Needing these medicines means the heart and blood vessels need protecting from extra strain, which psilocybin adds. Talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Goodwin et al. 2023. Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication. Neuropsychopharmacology",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10425429/",
     "pmid": "37443386"
    },
    {
     "title": "Griffiths et al. 2016. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5367557/",
     "pmid": "27909165"
    },
    {
     "title": "Toprol-XL (metoprolol) prescribing information: abrupt cessation",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=496ddfaa-7c9c-4888-b747-a210249b367a",
     "pmid": null
    },
    {
     "title": "Catapres-TTS (clonidine) prescribing information: withdrawal",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=39e1d35e-533c-4647-8649-8168a6e92dfa",
     "pmid": null
    },
    {
     "title": "Halman et al. 2024. Drug-drug interactions involving classic psychedelics: a systematic review. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10851641/",
     "pmid": "37982394"
    }
   ]
  },
  {
   "id": "lamotrigine",
   "class": "Lamotrigine",
   "examples": [
    "lamotrigine"
   ],
   "summary": "None of 34 online reports of lamotrigine taken with a classic psychedelic described seizures, and 65% were judged not to change the experience (Nayak 2021). This is a small, self-selected sample, not proof of safety. The lamotrigine label warns against abrupt discontinuation because of withdrawal seizures.",
   "evidence_level": "observational or survey",
   "direction": "unclear",
   "what_it_means": "No seizure signal in one small report set. Talk to your prescriber or pharmacist; never stop lamotrigine abruptly because of withdrawal seizure risk.",
   "sources": [
    {
     "title": "Nayak et al. 2021. Classic psychedelic coadministration with lithium, but not lamotrigine, is associated with seizures. Pharmacopsychiatry 54(5):240-245",
     "url": "https://pubmed.ncbi.nlm.nih.gov/34348413/",
     "pmid": "34348413"
    },
    {
     "title": "Lamictal XR (lamotrigine) prescribing information: withdrawal seizures",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3e2c9a35-6a39-41d7-ad84-3c0bb8894b09",
     "pmid": null
    }
   ]
  },
  {
   "id": "other-anticonvulsants",
   "class": "Other anticonvulsants and mood stabilizers",
   "examples": [
    "valproate (divalproex)",
    "carbamazepine",
    "oxcarbazepine",
    "phenytoin",
    "topiramate",
    "gabapentin",
    "pregabalin"
   ],
   "summary": "No human data on psilocybin with these drugs were found. Usona's phase 2 protocol excluded people who could not stop UGT enzyme modulators such as valproate, because glucuronidation is a major route for clearing psilocin; valproate is known to slow glucuronidation of some drugs (its label reports lamotrigine half-life rising from 26 to 70 hours). Imperial's protocol listed mood stabilisers as possibly attenuating psilocybin. Epilepsy itself is excluded in every major trial.",
   "evidence_level": "pharmacological theory",
   "direction": "unclear",
   "what_it_means": "No direct data, and the conditions these medicines treat are trial exclusions. Talk to your prescriber or pharmacist; never stop an anticonvulsant abruptly because of withdrawal seizure risk.",
   "sources": [
    {
     "title": "Usona PSIL201 protocol v10.0 (NCT03866174), exclusion criteria",
     "url": "https://cdn.clinicaltrials.gov/large-docs/74/NCT03866174/Prot_000.pdf",
     "pmid": null
    },
    {
     "title": "Manevski et al. 2010. Glucuronidation of psilocin and 4-hydroxyindole by the human UDP-glucuronosyltransferases. Drug Metab Dispos",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC2835393/",
     "pmid": "20007669"
    },
    {
     "title": "Depakote (divalproex) prescribing information: drug interactions",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=08a65cf4-7749-4ceb-6895-8f4805e2b01f",
     "pmid": null
    },
    {
     "title": "Imperial psilocybin vs escitalopram protocol v7 (NCT03429075)",
     "url": "https://cdn.clinicaltrials.gov/large-docs/75/NCT03429075/Prot_000.pdf",
     "pmid": null
    }
   ]
  },
  {
   "id": "cannabis",
   "class": "Cannabis",
   "examples": [
    "cannabis",
    "THC products"
   ],
   "summary": "In a prospective online survey (n = 321), cannabis used together with a psychedelic was associated with more intense experiences in a dose-related way, and with a curved (quadratic) relationship to challenging-experience scores. A global survey of emergency treatment after mushroom use found mixing substances among the most reported reasons for incidents. Usona's trial required participants to abstain from cannabis.",
   "evidence_level": "observational or survey",
   "direction": "changes",
   "what_it_means": "Cannabis may intensify the experience, including difficult parts. If you take prescribed medicines, talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Kuc et al. 2022. Psychedelic experience dose-dependently modulated by cannabis: results of a prospective online survey. Psychopharmacology",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9110465/",
     "pmid": "34734314"
    },
    {
     "title": "Kopra et al. 2022. Adverse experiences resulting in emergency medical treatment seeking following the use of magic mushrooms. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9353971/",
     "pmid": "35388724"
    },
    {
     "title": "Usona PSIL201 protocol v10.0 (NCT03866174), exclusion criteria",
     "url": "https://cdn.clinicaltrials.gov/large-docs/74/NCT03866174/Prot_000.pdf",
     "pmid": null
    }
   ]
  },
  {
   "id": "alcohol",
   "class": "Alcohol",
   "examples": [
    "beer",
    "wine",
    "spirits"
   ],
   "summary": "In a small study (n = 15), psilocybin blunted how intoxicated alcohol felt, while psilocybin effects were unchanged for 80% of participants. A Dutch risk review flagged combined use with alcohol as a concern. Multiple-drug toxicity accounted for 20% of psilocybin-related deaths in Australian coronial data, and polysubstance exposure was linked to hospital admission in US poison-center data on mushroom edibles (aOR 2.58).",
   "evidence_level": "observational or survey",
   "direction": "unclear",
   "what_it_means": "Alcohol may feel weaker than it is, and mixing is linked to worse outcomes in poison-center data. If you take prescribed medicines, talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Barrett et al. 2000. Hallucinogenic drugs attenuate the subjective response to alcohol in humans. Hum Psychopharmacol",
     "url": "https://pubmed.ncbi.nlm.nih.gov/12404626/",
     "pmid": "12404626"
    },
    {
     "title": "Halman et al. 2024. Drug-drug interactions involving classic psychedelics: a systematic review. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10851641/",
     "pmid": "37982394"
    },
    {
     "title": "van Amsterdam et al. 2011. Harm potential of magic mushroom use: a review. Regul Toxicol Pharmacol",
     "url": "https://pubmed.ncbi.nlm.nih.gov/21256914/",
     "pmid": "21256914"
    },
    {
     "title": "Darke et al. 2024. Characteristics and toxicology of LSD- and psilocybin-related death in Australia. Addiction",
     "url": "https://pubmed.ncbi.nlm.nih.gov/38771189/",
     "pmid": "38771189"
    },
    {
     "title": "Jorgenson et al. 2026. Psychoactive mushroom edibles: trends and toxicities reported to the US National Poison Data System, 2023-2024. Clin Toxicol",
     "url": "https://pubmed.ncbi.nlm.nih.gov/41493095/",
     "pmid": "41493095"
    }
   ]
  },
  {
   "id": "st-johns-wort",
   "class": "St John's wort",
   "examples": [
    "St John's wort (Hypericum perforatum)"
   ],
   "summary": "No psilocybin-specific data were found. St John's wort is serotonergic (the lithium label lists it as raising serotonin syndrome risk) but is not a meaningful brain MAO-A inhibitor on PET (under 5% occupancy vs 74% for moclobemide). NCCIH warns it weakens many medicines and can cause serious serotonin-related effects with some antidepressants.",
   "evidence_level": "pharmacological theory",
   "direction": "unclear",
   "what_it_means": "It interacts with many prescription drugs. Tell your prescriber or pharmacist about any supplement. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Sacher et al. 2011. MAO-A inhibitor occupancy during treatment with moclobemide or St John's wort: [11C]-harmine PET study. J Psychiatry Neurosci",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3201991/",
     "pmid": "21463543"
    },
    {
     "title": "NCCIH: St. John's Wort (last updated May 2025)",
     "url": "https://www.nccih.nih.gov/health/st-johns-wort",
     "pmid": null
    },
    {
     "title": "Lithium carbonate prescribing information (serotonin syndrome warning)",
     "url": "https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=01c4facd-ed79-4078-ba33-2044de372d0f",
     "pmid": null
    }
   ]
  },
  {
   "id": "mdma",
   "class": "MDMA",
   "examples": [
    "MDMA",
    "ecstasy",
    "molly"
   ],
   "summary": "A prospective convenience sample (27 co-users among 698 people) linked low-amount MDMA co-use with less intense challenging experiences; it was small and non-experimental. In a controlled LSD study, adding MDMA made LSD effects last about 1.5 hours longer, attributed to CYP2D6 inhibition, which matters less for psilocin. MDMA has its own serious risks, including deaths when combined with MAOIs, and chronic heavy use is linked to heart valve disease.",
   "evidence_level": "observational or survey",
   "direction": "unclear",
   "what_it_means": "No controlled safety data exist for this combination, and MDMA's own risks multiply with MAOIs. If you take prescribed medicines, talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Zeifman et al. 2023. Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences. Sci Rep",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10444769/",
     "pmid": "37608057"
    },
    {
     "title": "Halman et al. 2024. Drug-drug interactions involving classic psychedelics: a systematic review. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10851641/",
     "pmid": "37982394"
    },
    {
     "title": "Rached et al. 2026. Safety and efficacy of MAOIs in patients who use psychoactive substances. CNS Drugs",
     "url": "https://pubmed.ncbi.nlm.nih.gov/41546846/",
     "pmid": "41546846"
    },
    {
     "title": "Tagen et al. 2023. The risk of chronic psychedelic and MDMA microdosing for valvular heart disease. J Psychopharmacol",
     "url": "https://pubmed.ncbi.nlm.nih.gov/37572027/",
     "pmid": "37572027"
    },
    {
     "title": "Thomann et al. 2024. In vitro and in vivo metabolism of psilocybin's active metabolite psilocin. Front Pharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11089204/",
     "pmid": "38741590"
    }
   ]
  },
  {
   "id": "ketamine",
   "class": "Ketamine and esketamine",
   "examples": [
    "ketamine",
    "esketamine"
   ],
   "summary": "No human data on psilocybin combined with ketamine or esketamine were found. COMP001 excluded people who had received ketamine for their current depressive episode. Any added cardiovascular effect is theoretical and unconfirmed.",
   "evidence_level": "pharmacological theory",
   "direction": "unclear",
   "what_it_means": "No data. If you receive ketamine or esketamine treatment, talk to the prescriber running it before any decision involving psilocybin. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "COMPASS COMP001 protocol v4.0 (NCT03775200)",
     "url": "https://cdn.clinicaltrials.gov/large-docs/00/NCT03775200/Prot_000.pdf",
     "pmid": null
    }
   ]
  },
  {
   "id": "other-psychedelics",
   "class": "Other psychedelics",
   "examples": [
    "LSD",
    "DMT",
    "mescaline",
    "5-MeO-DMT",
    "2C-B",
    "Amanita muscaria products"
   ],
   "summary": "Combining psychedelics has no controlled safety data. In US poison-center data for 2024, psilocybin mushrooms appeared in two deaths, both with LSD ranked as the main substance. Reoccurring drug-like experiences were reported by 14.3% of healthy volunteers given both LSD and psilocybin vs 8.3% for psilocybin alone. Serious reactions and a death have been reported with 5-MeO-DMT combined with MAO-inhibiting harmala alkaloids.",
   "evidence_level": "observational or survey plus case reports",
   "direction": "unclear",
   "what_it_means": "Combinations are unstudied and appear in poison-center and coroner records. If you take prescribed medicines, talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Beuhler et al. 2025. 2024 Annual Report of the National Poison Data System (NPDS): 42nd annual report. Clin Toxicol",
     "url": "https://pubmed.ncbi.nlm.nih.gov/41432769/",
     "pmid": "41432769"
    },
    {
     "title": "Darke et al. 2024. Characteristics and toxicology of LSD- and psilocybin-related death in Australia. Addiction",
     "url": "https://pubmed.ncbi.nlm.nih.gov/38771189/",
     "pmid": "38771189"
    },
    {
     "title": "Muller et al. 2022. Flashback phenomena after administration of LSD and psilocybin in controlled studies with healthy participants. Psychopharmacology",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9166883/",
     "pmid": "35076721"
    },
    {
     "title": "Halman et al. 2024. Drug-drug interactions involving classic psychedelics: a systematic review. J Psychopharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10851641/",
     "pmid": "37982394"
    }
   ]
  },
  {
   "id": "metabolism",
   "class": "Drugs affecting psilocin metabolism (UGT, MAO-A, CYP2D6, CYP3A4)",
   "examples": [
    "valproate (UGT inhibition)",
    "strong MAO-A inhibitors",
    "strong CYP2D6 inhibitors (for example fluoxetine)",
    "strong CYP3A4 inhibitors (for example ketoconazole)"
   ],
   "summary": "Psilocybin is converted to psilocin, which is cleared by glucuronidation and by an oxidative pathway that starts with MAO-A; studies differ on which handles more. For glucuronidation, UGT1A10 (mostly in the gut) has the highest activity and UGT1A9 is likely the main liver enzyme. Of eight CYP enzymes only CYP2D6 and CYP3A4 metabolized psilocin in vitro; CYP2D6 genotype did not change psilocin blood levels in people. Free psilocin's half-life is about 1.4 to 1.8 hours, and escitalopram did not change its pharmacokinetics. Whether any specific drug raises psilocin exposure in people is unconfirmed.",
   "evidence_level": "pharmacological theory (in vitro and human pharmacokinetic data)",
   "direction": "unclear",
   "what_it_means": "Metabolic interactions are possible in theory but unmeasured. A pharmacist can check whether any medicine you take affects these enzymes. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Manevski et al. 2010. Glucuronidation of psilocin and 4-hydroxyindole by the human UDP-glucuronosyltransferases. Drug Metab Dispos",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC2835393/",
     "pmid": "20007669"
    },
    {
     "title": "Thomann et al. 2024. In vitro and in vivo metabolism of psilocybin's active metabolite psilocin. Front Pharmacol",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC11089204/",
     "pmid": "38741590"
    },
    {
     "title": "Dinis-Oliveira 2017. Metabolism of psilocybin and psilocin: clinical and forensic toxicological relevance. Drug Metab Rev",
     "url": "https://pubmed.ncbi.nlm.nih.gov/28074670/",
     "pmid": "28074670"
    },
    {
     "title": "Holze et al. 2023. Pharmacokinetics and pharmacodynamics of oral psilocybin administration in healthy participants. Clin Pharmacol Ther",
     "url": "https://pubmed.ncbi.nlm.nih.gov/36507738/",
     "pmid": "36507738"
    },
    {
     "title": "Becker et al. 2022. Acute effects of psilocybin after escitalopram or placebo pretreatment: randomized, double-blind, placebo-controlled crossover study. Clin Pharmacol Ther",
     "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9299061/",
     "pmid": "34743319"
    },
    {
     "title": "Usona PSIL201 protocol v10.0 (NCT03866174), exclusion criteria",
     "url": "https://cdn.clinicaltrials.gov/large-docs/74/NCT03866174/Prot_000.pdf",
     "pmid": null
    }
   ]
  },
  {
   "id": "unlabeled-products",
   "class": "Mushroom products with unlisted or unknown ingredients",
   "examples": [
    "mushroom chocolates",
    "gummies",
    "syrups",
    "products sold as legal or microdose supplements"
   ],
   "summary": "US poison centers reported a 2024 surge in exposures to products marketed as psychedelic mushrooms; some recalled products contained O-acetylpsilocin, psilocin, kavalactones, pregabalin and muscimol. From 2010 to 2024 there were 1,195 processed mushroom product exposures, 21.6% in children under 13. In 2023 to 2024 edible data, polysubstance exposure (aOR 2.58), confusion and CNS depression were linked to hospital admission. Alkaloid content of non-standardized products can vary by more than tenfold.",
   "evidence_level": "observational or survey (poison-center data)",
   "direction": "serious",
   "what_it_means": "When contents are unknown, interactions with your medicines cannot be predicted. If you take prescribed medicines, talk to your prescriber or pharmacist. Do not stop or change a prescribed medicine on your own: stopping some medicines abruptly can cause withdrawal effects or relapse.",
   "sources": [
    {
     "title": "Beuhler et al. 2025. 2024 Annual Report of the National Poison Data System (NPDS): 42nd annual report. Clin Toxicol",
     "url": "https://pubmed.ncbi.nlm.nih.gov/41432769/",
     "pmid": "41432769"
    },
    {
     "title": "Jorgenson et al. 2026. Psychoactive mushroom edibles: trends and toxicities reported to the US National Poison Data System, 2023-2024. Clin Toxicol",
     "url": "https://pubmed.ncbi.nlm.nih.gov/41493095/",
     "pmid": "41493095"
    },
    {
     "title": "Szarpak et al. 2026. Cardiovascular safety of psilocybin in psychiatric practice: a narrative review. Eur J Clin Pharmacol",
     "url": "https://pubmed.ncbi.nlm.nih.gov/42538465/",
     "pmid": "42538465"
    }
   ]
  }
 ]
}