Psilocybin interaction checker

Lithium, MAOIs and ayahuasca, antidepressants, stimulants, tramadol and more: the risk level, what is known and the study behind it.

• Lithium Avoid: dangerous

  For example Lithobid, Camcolit, Priadel

  In an analysis of online reports, 47% of 62 reports of lithium taken with a classic psychedelic such as psilocybin or LSD involved seizures, and 39% involved medical attention. Oregon's licensed programme turns away anyone who has taken lithium in the last 30 days. [Classic psychedelic coadministration with lithium, but not lamotrigine, is associated with seizures: an analysis of online psychedelic experience reports, Pharmacopsychiatry, 2021, read 28 October 2026] [Client Information Form (Oregon Psilocybin Services), Oregon Health Authority, 2026, read 28 October 2026]

  Avoid the combination. Talk to your prescriber. Never stop a prescribed medicine abruptly on your own.

• MAOIs, ayahuasca, Syrian rue Avoid: dangerous

  For example phenelzine, tranylcypromine, moclobemide, selegiline; ayahuasca, Syrian rue, harmala extracts (“psilohuasca”)

  A review of serotonin toxicity found that true serotonin toxicity typically occurs when a drug that raises serotonin is combined with an MAOI, and rated combinations without an MAOI as low risk. Ayahuasca contains MAO inhibitors, and Syrian rue seed extracts are potent MAO-A inhibitors. [Serotonin toxicity of serotonergic psychedelics, Psychopharmacology, 2022, read 28 October 2026] [Human hallucinogen research: guidelines for safety, Journal of Psychopharmacology, 2008, read 28 October 2026] [beta-Carboline alkaloids in Peganum harmala and inhibition of human monoamine oxidase (MAO), Food and Chemical Toxicology, 2010, read 28 October 2026]

  Avoid. Do not combine psilocybin with ayahuasca, Syrian rue or any harmala product, and do not take it while on an MAOI antidepressant. Talk to your prescriber. Never stop a prescribed medicine abruptly on your own.

• Tramadol High risk

  For example Ultram, Tramal

  We found no study of tramadol with psilocybin. Tramadol's prescribing information warns that seizures can occur within the recommended dose range, with higher risk alongside other drugs such as antidepressants, and that a potentially life-threatening serotonin syndrome can follow when it is taken with other serotonergic drugs. [Tramadol hydrochloride extended-release tablets: prescribing information, DailyMed, US National Library of Medicine, 2025, read 28 October 2026]

  Avoid the combination. Talk to your prescriber. Never stop a prescribed medicine abruptly on your own.

• Tricyclic antidepressants Caution

  For example amitriptyline, nortriptyline, clomipramine

  A small questionnaire study of people taking LSD (not psilocybin) found chronic tricyclic use was associated with subjectively stronger physical, hallucinatory and psychological responses. We found no direct study with psilocybin. [Alterations in responses to LSD in humans associated with chronic administration of tricyclic antidepressants, monoamine oxidase inhibitors or lithium, Behavioural Brain Research, 1996, read 28 October 2026]

  Effects may be stronger, not weaker. Talk to your prescriber. Never stop a prescribed medicine abruptly on your own.

• Benzodiazepines Caution

  For example diazepam, lorazepam, alprazolam, clonazepam

  Research safety guidelines name a benzodiazepine (10 mg of oral diazepam) as the drug treatment of choice for severe anxiety during a session. There is little research on taking psilocybin while on a regular benzodiazepine. [Human hallucinogen research: guidelines for safety, Journal of Psychopharmacology, 2008, read 28 October 2026]

  Effects may be dampened. Do not stop or change a regular benzodiazepine without your prescriber. Talk to your prescriber. Never stop a prescribed medicine abruptly on your own.

• Stimulants and ADHD medicines Caution

  For example amphetamine, methylphenidate, cocaine, high-dose caffeine

  Psilocybin typically raises blood pressure and heart rate. We found little direct research on combining it with stimulants, which can also raise both; research guidelines note that stimulants such as cocaine can cause cardiac stress. [Psilocybin (Magic Mushrooms), National Institute on Drug Abuse, read 28 October 2026] [Human hallucinogen research: guidelines for safety, Journal of Psychopharmacology, 2008, read 28 October 2026]

  Avoid stacking stimulants on the day. Talk to your prescriber. Never stop a prescribed medicine abruptly on your own.

• Cannabis Caution

  The Dutch drug information service advises against combining mushrooms with other drugs, and says cannabis can make a trip stronger, longer or less controllable. [Paddo's: combinatiegebruik, DRUGSinfo, Trimbos-instituut, read 28 October 2026]

  Avoid on the day, especially during the session.

• Alcohol Caution

  The same service says alcohol increases the chance of a bad trip. [Paddo's: combinatiegebruik, DRUGSinfo, Trimbos-instituut, read 28 October 2026]

  No alcohol on the day, and ideally for a few days before.

• Beta blockers and heart medicines Caution

  For example metoprolol, propranolol, blood pressure medicines

  We found little research on these medicines with psilocybin. The concern is the condition behind them: psilocybin typically raises blood pressure and heart rate, and research screening requires good general health checked with an ECG, with blood pressure monitored throughout sessions. [Psilocybin (Magic Mushrooms), National Institute on Drug Abuse, read 28 October 2026] [Human hallucinogen research: guidelines for safety, Journal of Psychopharmacology, 2008, read 28 October 2026]

  If you take a heart or blood pressure medicine, a clinical or licensed setting with screening is the safer route. Talk to your prescriber. Never stop a prescribed medicine abruptly on your own.

• SSRIs Effects likely weaker

  For example sertraline, fluoxetine, escitalopram, citalopram, paroxetine

  In a survey of 611 reports of taking mushrooms with an antidepressant, the probability of weaker than expected effects was 0.47 for SSRIs, and blunting was reported for up to three months after stopping. The serotonin toxicity review rates serotonergic drugs without MAOIs as low risk with psilocybin. [Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use, Journal of Psychopharmacology, 2023, read 28 October 2026] [Serotonin toxicity of serotonergic psychedelics, Psychopharmacology, 2022, read 28 October 2026] [Deciding to take ayahuasca, ICEERS, 2018, read 28 October 2026]

  Expect weaker effects; do not take more to compensate. Do not stop an SSRI on your own: stopping psychiatric medicine abruptly can be dangerous. Talk to your prescriber. Never stop a prescribed medicine abruptly on your own.

• SNRIs Effects likely weaker

  For example venlafaxine, duloxetine, desvenlafaxine

  In the same survey, the probability of weaker than expected effects was 0.55 for SNRIs, and blunting was reported for up to three months after stopping. [Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use, Journal of Psychopharmacology, 2023, read 28 October 2026]

  Expect weaker effects. Talk to your prescriber. Never stop a prescribed medicine abruptly on your own.

• Bupropion Effects likely weaker

  For example Wellbutrin, Zyban

  In the survey of 611 reports, the probability of weaker than expected effects with bupropion was 0.29, lower than for SSRIs (0.47) or SNRIs (0.55). [Attenuation of psilocybin mushroom effects during and after SSRI/SNRI antidepressant use, Journal of Psychopharmacology, 2023, read 28 October 2026]

  Effects may be somewhat weaker. Talk to your prescriber. Never stop a prescribed medicine abruptly on your own.

• Antipsychotics Effects likely weaker

  For example risperidone, quetiapine, olanzapine, haloperidol

  In a placebo-controlled study, psilocybin's psychosis-like effects were blocked in a dose-dependent way by risperidone, but increased by the older antipsychotic haloperidol. Research screening also excludes people with a history of psychotic disorders. [Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action, NeuroReport, 1998, read 28 October 2026] [Human hallucinogen research: guidelines for safety, Journal of Psychopharmacology, 2008, read 28 October 2026]

  Effects may be blocked or, with some antipsychotics, made stronger, and the reason you take an antipsychotic is itself a reason to avoid psilocybin outside a clinical setting. Talk to your prescriber. Never stop a prescribed medicine abruptly on your own.

• St John's Wort Little evidence: caution

  For example Hypericum perforatum supplements

  We found no study of St John's Wort with psilocybin. The Johns Hopkins safety guidelines say it may affect serotonin function and that excluding people who take it is appropriate. The US National Center for Complementary and Integrative Health warns that taking it with antidepressants or other drugs that affect serotonin may lead to serious serotonin-related side effects. [Human hallucinogen research: guidelines for safety, Journal of Psychopharmacology, 2008, read 28 October 2026] [St. John's Wort, National Center for Complementary and Integrative Health, read 28 October 2026]

  Treat it as a serotonergic medicine. Tell your doctor you take it.