A reference work, not a recommendation to use: this profile describes mechanism and evidence and does not replace medical advice. The claims come from marketing and forums and are tested here, not endorsed. Manufacture, possession, trade or use may be prohibited; see “Legal status” for details.

Claims checked

  • Helps against depression, even when other treatments have failed

    Proven benefit

    Mood & stress · Patients: depression, also treatment-resistant · Human, randomised

    Short-term benefit in RCTs: 6.6 MADRS points difference after three weeks in treatment-resistant depression, but hardly any sustained response to week 12 (manufacturer-funded) [7]; versus escitalopram no significant difference in the primary endpoint [8]; meta-analysis g 0.66 at moderate certainty, larger effects with self-rating and prior experience [9]. Blinding is hardly possible when the effect is noticeable.

  • Microdosing lifts mood and well-being

    No benefit

    Mood & stress · healthy · Human, randomised

    In the largest placebo-controlled study (191 participants), the microdosing and placebo groups improved equally [11]. A meta-analysis of the RCTs found no difference in depressive symptoms (SMD −0.19), anxiety, or stress [13].

  • Microdosing increases creativity

    Single unconfirmed finding

    Cognition & focus · healthy · Human, randomised

    Pooled analysis of three RCTs (171 participants): only the ratio of original to all responses rose, other measures of divergent thinking and convergent thinking did not [12]. Small acute creativity effects in another study can be explained by unblinding [11]; a meta-analysis sees hardly any effect on cognition and creativity [13].

  • Helps with quitting alcohol dependence

    Single unconfirmed finding

    Addiction & dependence · Patients: alcohol dependence · Human, randomised small studiesEvery study behind this level and result had fewer than 100 participants. Small studies report larger effects on average than large ones, so the result is less certain.

    An RCT with 95 participants and an active placebo (diphenhydramine), each with psychotherapy: 9.7% versus 23.6% heavy drinking days over 32 weeks [10]. Confirmation in a second large study is pending.

  • Promotes neuroplasticity and “rewires the brain”

    Not studied

    Recovery & healing · healthy · Animal study

    Animal data only: in stressed mice, a single dose strengthened excitatory synapses in the hippocampus [5]. Whether this happens in humans and is associated with a benefit has not been studied.

small studies: Every study behind this level and result had fewer than 100 participants. Small studies report larger effects on average than large ones, so the result is less certain.

Mechanism of action

Evidence map: Psilocybin

Each line stands for a published finding; line style and color show where it comes from. The filter hides weaker evidence levels. Sources: see references.

Psilocybin is a tryptamine alkaloid from mushrooms of the genus Psilocybe and is itself a precursor (prodrug): after swallowing, no psilocybin was found in plasma or urine in healthy people, only the active metabolite psilocin [1]. Even after intravenous administration, psilocin reached its peak after only about two minutes; the phosphate group is thus cleaved off very quickly [2]. Psilocin is an agonist at the serotonin 2A receptor (5-HT2A). In a PET study with eight healthy people, it occupied up to 72% of brain 5-HT2A receptors in a dose-dependent manner, and both occupancy and the plasma psilocin level were closely related to the experienced intensity [3]. The 5-HT2A antagonist ketanserin abolished the psychosis-like effects in humans in a dose-dependent manner, while the dopamine antagonist haloperidol tended to intensify them [4].

Whether the antidepressant effect needs the same receptor is open: in chronically stressed mice, a single dose of psilocybin abolished anhedonia and strengthened excitatory synapses in the hippocampus, even when ketanserin had blocked the 5-HT2A receptor beforehand [5]. The half-life of psilocin in healthy people was about 3 hours [1], for free psilocin not bound to glucuronic acid 1.8 hours [6]. Two weeks of pretreatment with escitalopram did not change the pharmacokinetics, but attenuated anxiety and unpleasant effects [6].

In treatment-resistant depression, a high single dose with psychological support in a manufacturer-funded phase 2 study (233 participants) lowered the MADRS score by 6.6 points more than a very low control dose after three weeks; a sustained response to week 12 was hardly seen [7]. In a direct comparison with escitalopram (59 participants), the primary endpoint after six weeks did not differ significantly [8]. A meta-analysis of seven RCTs with 436 participants found a medium to large effect (Hedges' g 0.66) that was larger with self-rating and in people with prior psychedelic experience, which points to expectation effects [9]. In alcohol dependence, the proportion of heavy drinking days was lower in an RCT with an active placebo (9.7% versus 23.6%) [10].

For microdosing, i.e., repeated non-hallucinogenic doses, a self-blinded study with 191 participants found no differences from placebo [11]; a pooled analysis of three RCTs with 171 participants found an effect on only a single creativity measure [12], and a meta-analysis in healthy people found no clear benefit for mood, anxiety, or stress [13]. Physically, psilocybin is considered of low toxicity; in a worldwide online survey, 0.2% of users in a year sought emergency treatment, mostly because of anxiety, panic, or paranoia [14]. Risky are the combination with lithium (seizures in anecdotal reports) [15] and use with a predisposition to psychosis [16]. In Germany, psilocybin is a controlled substance not authorized for marketing [17], in the United States Schedule I [18].

Targets

TargetTypeActionKey dataEvidence
Serotonin 2A receptor (5-HT2A)ReceptorAgonistoccupancy up to 72% (human, PET with [11C]Cimbi-36, n = 8); occupancy and plasma psilocin correlate with intensity Human, non-randomised[3]
5-HT2A receptor as mediator of the psychedelic effectReceptorAgonistKetanserin and risperidone block the effects in a dose-dependent manner, haloperidol does not (human) Human, non-randomised[4]
Excitatory synapses in the hippocampusSignaling pathwayActivatorStrengthening after a single dose, not prevented by ketanserin (mouse, chronic stress) Animal study[5]

Effect profile

Which signaling systems the compound affects according to current data. ↑ enhanced, ↓ dampened, ≈ modulated, ○ no effect; dots = evidence level.

  • Dopamineunclear · Haloperidol did not block the psychosis-like effects but tended to intensify them; no indication of a dopamine-dependent mechanism[4]
  • Noradrenalineno data
  • Serotonin↑ · Psilocin activates 5-HT2A receptors; occupancy up to 72% on PET, effect blockable by ketanserin[3][4]
  • Acetylcholineno data
  • Glutamate · AMPA↑ · Stronger excitatory synapses in the hippocampus of stressed mice, independent of 5-HT2A[5]
  • Glutamate · NMDAno data
  • GABAno data
  • Histamineno data
  • Orexinno data
  • Adenosineno data
  • Opioidsno data
  • Melatoninno data
  • Neurotrophinsno data
  • Blood flowno data
  • Nitric oxideno data
  • Energy metabolismno data
  • Insulin · glucoseno data
  • Inflammation · oxidativeno data
  • Stress axisno data
  • Testosterone axisno data
  • Endocannabinoidsno data
  • Autophagy · senescenceno data
  • Immune systemno data
  • Lipid metabolismno data
  • Coagulation · fibrinolysisno data
  • Methylationno data

Routes of administration and bioavailability

How much of a compound reaches the blood or target tissue depends on the route into the body and on the dosage form. All routes of administration explained

  • Oral (swallowed) · synthetic psilocybin (studies) or mushrooms

    ≈ 53% as psilocin (human, n = 3)

    Psilocybin is completely converted to psilocin, no psilocybin is detectable in plasma [1]; peak level of psilocin after about 105 minutes [2]. The active ingredient content of mushrooms varies; data on this do not come from the cited studies.

    Human, non-randomised

  • Intravenous · only in studies

    Psilocin peak after about 2 minutes, i.e., very rapid dephosphorylation also in the blood [2].

    Human, non-randomised

Human studies

  • 5-HT2A occupancy on PET

    open PET study, single doses · healthy · n = 8 · single dose, measurement on the same day

    Measured: 5-HT2A occupancy, plasma psilocin, intensity

    Result: Occupancy up to 72%; occupancy and psilocin level correlate with intensity.[3]

    Human, non-randomised

  • Treatment-resistant depression (COMP360)

    RCT, double-blind, phase 2, three dose groups · Patients: treatment-resistant depression · n = 233 · single dose, 12 weeks of follow-up

    Measured: MADRS after 3 weeks

    Result: High dose −12.0 versus −5.4 points (difference −6.6; 95% CI −10.2 to −2.9); medium dose not significant; adverse events in 77%. Funded by COMPASS Pathfinder.[7]

    Human, randomised

  • Psilocybin versus escitalopram

    RCT, double-blind, phase 2 · Patients: moderate to severe depression · n = 59 · 6 weeks

    Measured: QIDS-SR-16

    Result: −8.0 versus −6.0 points, difference not significant (p = 0.17); secondary endpoints in favor of psilocybin, but without correction for multiple testing.[8]

    Human, randomised

  • Meta-analysis depression

    systematic review and meta-analysis of RCTs · Patients: clinically relevant depressive symptoms · n = 436 · 7 studies

    Measured: change in depression scores

    Result: Hedges' g 0.66 (95% CI 0.46–0.86), moderate certainty (GRADE).[9]

    Human, randomised

  • Alcohol dependence

    RCT, double-blind, active placebo · Patients: alcohol dependence · n = 95 · 32 weeks after first dose

    Measured: proportion of heavy drinking days

    Result: 9.7% versus 23.6% (difference 13.9 percentage points; 95% CI 3.0–24.7).[10]

    Human, randomised

  • Microdosing, self-blinded

    placebo-controlled, self-blinding (citizen science) · healthy (microdosing practitioners) · n = 191 · 4 weeks

    Measured: well-being, mood, cognition

    Result: Both groups improved, no difference between microdosing and placebo.[11]

    Human, randomised

  • Microdosing and creativity

    pooled analysis of 3 RCTs, double-blind · healthy · n = 171 · multiple doses

    Measured: divergent and convergent thinking

    Result: Only the originality/fluency ratio improved; other measures unchanged.[12]

    Human, randomised

  • Emergency treatments after mushroom use

    online survey (Global Drug Survey 2017) · People with mushroom use in the past year · n = 9233 · 12 months

    Measured: emergency treatment

    Result: 19 people (0.2%), risk per use 0.06%; mostly anxiety, panic, paranoia; almost all unremarkable again after 24 hours.[14]

    Human, non-randomised

Risks and warnings

  • Anxiety, panic, and psychological crises

    In a worldwide survey, 0.2% of users in a year sought emergency treatment, mostly because of anxiety, panic, or paranoia; poor state of mind, unfavorable setting, and polysubstance use were named as reasons [14]. Anyone who gets into a crisis will find help at a primary care practice or an addiction counseling service.

    Human, non-randomised

  • Suicidal thoughts in studies

    In the large phase 2 study in treatment-resistant depression, suicidal thoughts, suicidal behavior, or self-harm occurred in all groups, including the control group [7].

    Human, randomised

  • Psychosis with predisposition

    Psilocybin triggers a temporary psychosis-like state in healthy people [4]; a review names worsening of mental illness in people with (a predisposition to) psychosis and dangerous behavior without supervision as the main risks [16].

    Human, non-randomised

  • Seizures with lithium

    In 47% of 62 online anecdotal reports on classic psychedelics plus lithium, seizures were described, in 39% medical help; with lamotrigine (34 reports) none. Self-reported data only, but a clear warning signal [15].

    Human, non-randomised

  • Dependence

    According to a review, only a weak reinforcing effect; animals self-administer it hardly at all and only temporarily [16]. This argues against a high addiction potential, but not against acute risks.

    Animal study

Interactions

  • Lithium: Seizures in almost half of the evaluated anecdotal reports [15].
  • Escitalopram (SSRI): Pretreatment over 14 days reduced anxiety, unpleasant and cardiovascular effects, without changing positive mood effects or psilocin kinetics (RCT in healthy people) [6].
  • Ketanserin, risperidone, haloperidol: 5-HT2A blockers abolish the effects, haloperidol tends to intensify them [4].

Fact check: common claims

  • not supported

    “Microdosing makes you more creative and productive”

    Placebo-controlled studies find hardly any differences from placebo; only a single creativity measure improved [11][12][13].

  • partly supported

    “A single session cures depression permanently”

    Short-term improvement after three weeks in RCTs [7][9], but hardly any sustained response to week 12 [7] and no significant advantage over escitalopram [8].

  • partly supported

    “The effect arises via the serotonin 2A receptor”

    Documented for the psychedelic effect (PET, blockade by ketanserin) [3][4]; the antidepressant-like effect in mice persisted despite blockade [5].

  • refuted

    “Psilocybin is harmless because it is not addictive”

    The addiction potential is low [16], but there are emergencies due to anxiety and panic [14], seizures with lithium [15], and risks with a predisposition to psychosis [16].

Pharmacokinetics

Absorption
Prodrug: complete conversion to psilocin, no psilocybin in plasma [1]; oral bioavailability of psilocin about 53% (n = 3), peak level after about 105 minutes [2].
Half-life
Psilocin about 3 hours [1]; free psilocin 1.8 hours (1.1–2.2) [6].
Metabolism
Psilocin is glucuronidated; less than 2% is excreted unchanged via the kidney [1]. Escitalopram did not change the pharmacokinetics [6].
Entry into the brain
Centrally active: up to 72% 5-HT2A occupancy on PET [3].

Legal status

Germany
Controlled substance not authorized for marketing (Annex I of the German Narcotics Act, BtMG); a therapeutic use is conceivable only in studies or via hardship provisions (compassionate use) [17].
EU
No EU marketing authorization as a medicinal product; the classification under narcotics law is regulated by each member state itself [17].
USA
Schedule I of the Controlled Substances Act [18].
Other countries
Internationally, like other psychedelics, in Schedule I of the 1971 UN Convention on Psychotropic Substances [17].

Related compounds

LSD (Lysergsäurediethylamid)same class (German only)DMT (N,N-Dimethyltryptamin)analog (German only)

Open questions

  • How long does the antidepressant effect last, and how often would treatment be needed?
  • How much of the effect is due to expectation and unblinding?
  • Does the antidepressant effect in humans need the psychedelic experience (5-HT2A) or not?
  • How safe is psilocybin in people who are excluded from studies (bipolar disorder, psychosis risk)?

References

  1. Brown RT, Nicholas CR, Cozzi NV, Gassman MC, Cooper KM, Muller D, et al. Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Clin Pharmacokinet. 2017;56(12):1543–1554. doi:10.1007/s40262-017-0540-6 · PubMed
  2. Hasler F, Bourquin D, Brenneisen R, Bär T, Vollenweider FX. Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man. Pharm Acta Helv. 1997;72(3):175–84. doi:10.1016/s0031-6865(97)00014-9 · PubMed
  3. Madsen MK, Fisher PM, Burmester D, Dyssegaard A, Stenbæk DS, Kristiansen S, et al. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology. 2019;44(7):1328–1334. doi:10.1038/s41386-019-0324-9 · PubMed
  4. Vollenweider FX, Vollenweider-Scherpenhuyzen MF, Bäbler A, Vogel H, Hell D. Psilocybin induces schizophrenia-like psychosis in humans via a serotonin-2 agonist action. Neuroreport. 1998;9(17):3897–902. doi:10.1097/00001756-199812010-00024 · PubMed
  5. Hesselgrave N, Troppoli TA, Wulff AB, Cole AB, Thompson SM. Harnessing psilocybin: antidepressant-like behavioral and synaptic actions of psilocybin are independent of 5-HT2R activation in mice. Proc Natl Acad Sci U S A. 2021;118(17):e2022489118. doi:10.1073/pnas.2022489118 · PubMed
  6. Becker AM, Holze F, Grandinetti T, Klaiber A, Toedtli VE, Kolaczynska KE, et al. Acute Effects of Psilocybin After Escitalopram or Placebo Pretreatment in a Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Subjects. Clin Pharmacol Ther. 2022;111(4):886–895. doi:10.1002/cpt.2487 · PubMed
  7. Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, et al. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med. 2022;387(18):1637–1648. doi:10.1056/NEJMoa2206443 · PubMed
  8. Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Murphy R, et al. Trial of Psilocybin versus Escitalopram for Depression. N Engl J Med. 2021;384(15):1402–1411. doi:10.1056/NEJMoa2032994 · PubMed
  9. Metaxa AM, Clarke M. Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis. BMJ. 2024;385:e078084. doi:10.1136/bmj-2023-078084 · PubMed
  10. Bogenschutz MP, Ross S, Bhatt S, Baron T, Forcehimes AA, Laska E, et al. Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2022;79(10):953–962. doi:10.1001/jamapsychiatry.2022.2096 · PubMed
  11. Szigeti B, Kartner L, Blemings A, Rosas F, Feilding A, Nutt DJ, et al. Self-blinding citizen science to explore psychedelic microdosing. eLife. 2021;10:e62878. doi:10.7554/eLife.62878 · PubMed
  12. Prochazkova L, Marschall J, van Elk M, Rifkin BD, Schon NR, Fiacchino D, et al. Microdosing psilocybin and its effect on creativity: Lessons learned from three double-blind placebo controlled longitudinal trials. Neuropharmacology. 2026;284:110732. doi:10.1016/j.neuropharm.2025.110732 · PubMed
  13. Meshkat S, Leung M, Meshkat S, Lin Q, Wijendran D, Reichelt AC, et al. Efficacy and Safety of Psychedelic Microdosing on Psychological Outcomes in Healthy Adults: A Systematic Review and Meta-analysis. CNS Drugs. 2026;40(10):1369–1393. doi:10.1007/s40263-026-01325-5 · PubMed
  14. Kopra EI, Ferris JA, Winstock AR, Young AH, Rucker JJ. Adverse experiences resulting in emergency medical treatment seeking following the use of magic mushrooms. J Psychopharmacol. 2022;36(8):965–973. doi:10.1177/02698811221084063 · PubMed
  15. Nayak SM, Gukasyan N, Barrett FS, Erowid E, Erowid F, Griffiths RR. Classic Psychedelic Coadministration with Lithium, but Not Lamotrigine, is Associated with Seizures: An Analysis of Online Psychedelic Experience Reports. Pharmacopsychiatry. 2021;54(5):240–245. doi:10.1055/a-1524-2794 · PubMed
  16. Johnson MW, Griffiths RR, Hendricks PS, Henningfield JE. The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act. Neuropharmacology. 2018;142:143–166. doi:10.1016/j.neuropharm.2018.05.012 · PubMed
  17. Perez Rosal SR, La Torre JT, Birnkammer S, Chernoloz O, Williams MT, Faber SC. Expert recommendations for Germany's integration of psychedelic-assisted therapy. BMC Med Educ. 2024;24(1):1202. doi:10.1186/s12909-024-06141-3 · PubMed
  18. Henningfield JE, Coe MA, Griffiths RR, Belouin SJ, Berger A, Coker AR, et al. Psychedelic drug abuse potential assessment research for new drug applications and Controlled Substances Act scheduling. Neuropharmacology. 2022;218:109220. doi:10.1016/j.neuropharm.2022.109220 · PubMed
How this profile was checked

Last reviewed: 2026-10-24. All sources with a DOI or PMID were resolved automatically via Crossref or doi.org and PubMed.

Translated from the German profile (version of 2026-10-24); translation checked on 2026-10-26.

Checked

  • All abstracts read via PubMed; DOIs and PMIDs resolved with tools/pruefe_profile.py.
  • At the abstract: no psilocybin in plasma/urine, renal clearance of psilocin < 2%, t½ 3 h, n = 12 [1]; Tmax 105 ± 37 min oral, 1.9 min i.v., bioavailability 52.7 ± 20% (n = 3) [2]; n = 8, occupancy up to 72% [3]; blockade by ketanserin/risperidone, intensification by haloperidol [4]; mouse, ketanserin without influence [5]; free psilocin t½ 1.8 h (1.1–2.2), escitalopram without PK effect [6]; 79/75/79 participants, −12.0/−7.9/−5.4, difference −6.6 (−10.2 to −2.9), adverse events 77% [7]; n = 59, −8.0 vs. −6.0, p = 0.17, response 70 vs. 48%, remission 57 vs. 28% [8]; 436 participants, 7 of 9 studies, g 0.66 (0.46–0.86) [9]; n = 95, 9.7 vs. 23.6%, difference 13.9 (3.0–24.7) [10]; n = 191 [11]; N = 171 [12]; 24 studies, 3681 participants, SMD −0.19 [13]; 9233 users, 19 (0.2%), 0.06% per event [14]; 62 lithium reports, 47% seizures, 39% medical help, 34 lamotrigine reports [15].
  • In the full text (PMC11515625): psilocybin, LSD, MDMA, and mescaline as controlled substances not authorized for marketing under Annex I of the BtMG; classification in the EU national; 1971 UN Convention Schedule I [17]. US Schedule I in the abstract of [18].
  • Interests: [7] funded by COMPASS Pathfinder, several authors employed there; [8] Alexander Mosley Charitable Trust and Imperial College; [6] supported by University Hospital Basel and Mind Medicine, one author consultant to Mind Medicine; first author of [9] employed at IDEA Pharma; [10] among others Heffter Research Institute; [13] one author CMO of Mydecine; [14] Winstock is founder of the Global Drug Survey, King's College receives funds from COMPASS; [16] Griffiths on the board of the Heffter Research Institute, Henningfield advises Heffter and Usona; [5] patent application by the University of Maryland on psychedelics plus 5-HT2 antagonists.
  • ClinicalTrials.gov: 325 entries for “psilocybin” (October 24, 2026), none from the sponsor “Hudson Biotech”.
  • Precision flags (m004, implemented by Claude October 26, 2026, pending confirmation by Tilman): “Helps with quitting alcohol dependence” → “kleine_studien”: [10] 95 randomized (abstract).

Not verified

  • Sample size in [4] and [6] is not in the abstract.
  • Receptor values (Ki) of psilocin at 5-HT2A, 5-HT2C, 5-HT1A not checked against a primary source with figures; therefore only PET occupancy is given.
  • Australia: prescription by authorized psychiatrists for treatment-resistant depression since July 1, 2023 according to Nutt et al., Br J Pharmacol 2026 (PMID 39701143); not included in the profile because of the reference limit.
  • German hardship program (Lancet Psychiatry 2026, PMID 40976246) without an abstract, content not checked.
  • Differing active ingredient content of mushrooms and confusion with poisonous mushrooms not checked against primary sources.

No dosages, no sources of supply. This information does not replace medical advice.

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