Psilocybin mushrooms

No human lethal dose has been established; acute physical toxicity is negligible at pharmacologically relevant dosessupported

For LSD and psilocybin: no dose has been established above which lives are endangered. toxics11020148

One HPPD case followed combined psilocybin and cannabis usesupported

Case report: 18-year-old male developed HPPD after mixed psilocybin+cannabis intoxication. pmid:15963699

A systematic toxicology review of psychedelics concluded that no dose has been identified above which psilocybin endangers human lifesupported

For LSD and psilocybin: no dose has been established above which lives are endangered. toxics11020148

The acute physical adverse event profile from clinical trial populations (598 patients across 44 studies) is characterized by:supported

Systematic review of 44 articles (34 quantitative + 10 qualitative) on adverse events in 598 unique patients. 02698811221116926

The Raison et al. 2023 JAMA trial found a higher overall adverse event rate with 25 mg psilocybin versus niacin placebo — consistent with mild physiological burden — but no serious treatment-emergent adverse events.supported

No serious treatment-emergent AEs. Higher rate of overall and severe AEs vs niacin. jama.2023.14530

A case series of Psilocybe keralensis poisonings in China documented myocardial injury with cardiovascular complications, suggesting species-specific toxicity at high doses — these findings have not been replicated with P. cubensis or other commonly consumed species.supported

Case series of Psilocybe keralensis poisoning in China. Notable cardiovascular complications including myocardial injury. 15563650.2025.2552438

NPDS 2023–2024 data document unregulated products with unlisted ingredients and inconsistent formulationssupported

Unregulated products with often unlisted ingredients and inconsistent formulations. 15563650.2025.2599402

Analysis of 409 psilocybin administrations in controlled settings identified drug dose as the single most important predictor of all acute response variables.supported

Analysis of 409 psilocybin administrations in 261 healthy volunteers across 23 studies. Drug dose is primary predictor of all response variables. journal.pone.0030800

In a nationally representative US adult sample (N = 2,822; 613 lifetime classic psychedelic users): 59.1% reported no challenging experiences; 8.9% experienced functional impairment lasting more than one day from their most challenging experience; and 2.6% sought medical or psychiatric assistancesupported

Nationally representative US adult data (N=2,822). 613 lifetime classic psychedelic users. 59.1% had no challenging experiences; 8.9% had functional impairment >1 day; 2.6% sought medical help. j.jad.2023.01.073

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

Historical clinical data indicate psilocybin is not helpful in established psychotic disorders and may precipitate or exacerbate psychotic episodes in vulnerable individuals. The causal relationship between psilocybin and precipitated psychosis in genetically predisposed individuals is documented in case reports and expert consensus, but well-controlled prospective data are limited.supported

Historical review: classical psychedelics (psilocybin, LSD, mescaline) used extensively in psychiatry pre-1967 UN scheduling. Not helpful for established psychotic disorders. j.neuropharm.2017.12.040

At least one case report describes HPPD persisting more than 8 months following combined psilocybin and cannabis usesupported

Case report: 18-year-old male developed HPPD after mixed psilocybin+cannabis intoxication. Symptomatic recurrences persisting >8 months. pmid:15963699

Controlled study data attribute flashback phenomena less strongly to psilocybin than to LSDsupported

Investigation of flashback/HPPD phenomena in controlled LSD and psilocybin trials. Limited data; phenomenon attributed more to LSD. s00213-022-06066-z

Claim in safety — inconclusiveinconclusiveworking →

Cross-tolerance is complete with LSD and other serotonergic hallucinogens (mescaline, DMT) but does not extend to non-serotonergic psychoactive substancessupported

Reviews evidence for 5-HT2A as primary site of hallucinogen action; cross-tolerance between psilocybin, LSD, mescaline. j.bbr.2014.07.016

Physical dependence: Serotonergic psychedelics including psilocybin do not produce physical dependence or withdrawal syndromes with repeated usesupported

Serotonergic psychedelics including psilocybin do not produce physical dependence or withdrawal symptoms with repeated use. j.pnpbp.2024.111129

Physical dependence: Serotonergic psychedelics including psilocybin do not produce physical dependence or withdrawal syndromes with repeated usesupported

No physical dependence or withdrawal symptoms with repeated use. j.neubiorev.2025.106163

Claim in safety — not_supportednot supportedworking →

Abuse potential: Classified as low by clinical experts, consistent with the pharmacological profile (rapid tolerance, no dopaminergic reward sensitization, absence of physical withdrawal).supported

Serotonergic psychedelics including psilocybin do not produce physical dependence or withdrawal symptoms with repeated use. j.pnpbp.2024.111129

Co-use of lithium or other mood stabilizers with psilocybin is the strongest predictor of challenging experiences and overall harm in population epidemiological datasupported

Co-use of lithium/mood stabilizers strongly associated with greater difficulty and overall harm risk. j.jad.2023.01.073

Co-administration of MAOIs with psilocybin mushrooms is associated with hypertensive urgency or emergency, documented in a narrative review synthesizing case reportssupported

MAOI + psilocybin mushrooms associated with hypertensive urgency/emergency in case reports. Synthesizes 219 publications including 56 case reports. s40263-025-01256-7

A Phase 2 exploratory study of 25 mg COMP360 psilocybin with concurrent SSRI use in 19 participants found mild adverse events only and no serious eventssupported

Phase II exploratory study of COMP360 (synthetic psilocybin 25mg) with concurrent SSRI. 19 participants. Mild TEAEs only; no serious AEs. s41386-023-01648-7

Psilocin is metabolized by CYP2D6 and CYP3A4supported

Primary metabolism by CYP2D6 and CYP3A4. pharmaceutics17040411

Claim in safety — inconclusiveinconclusiveworking →

Claim in safety — inconclusiveinconclusiveworking →

The P. keralensis myocardial injury case series raises additional concern about cardiovascular vulnerability at high doses. Relative contraindication — risk-benefit assessment required, particularly in individuals with uncontrolled hypertension or recent cardiac events.supported

Case series of Psilocybe keralensis poisoning in China. Notable cardiovascular complications including myocardial injury. 15563650.2025.2552438

Standard workplace immunoassay drug panels (SAMHSA-5, EMIT, FPIA) do not detect psilocybin or psilocinsupported

No routine immunoassay screens for psilocybin/psilocin in standard urine drug testing panels. bs.acc.2016.07.004

The amphetamine/methamphetamine immunoassay shows minimal cross-reactivity with psilocin (1.3% at 50 mg/L in one DUID case)supported

Positive on fluorescence polarization immunoassay amphetamine/methamphetamine assay (1.3% cross-reactivity at 50 mg/L). pmid:16839473

Confirmation of psilocybin or psilocin exposure requires targeted GC-MS or LC-MS/MS analysissupported

GC-MS and LC-MS/MS needed for confirmation. bs.acc.2016.07.004

Claim in safety — inconclusiveinconclusiveworking →

A 2024 Nature study demonstrated that a single 25 mg dose of psilocybin produces massive desynchronization of functional brain connectivity — a broadband reduction in oscillatory power (1–100 Hz) across posterior association cortices and the default mode network (DMN), with functional connectivity changes exceeding three times those produced by methylphenidate in the same individualspartially supported

25mg psilocybin massively disrupts functional connectivity, strongest in default mode network. Persistent hippocampal-DMN connectivity decrease lasting weeks. s41586-024-07624-5

Psilocin, the active metabolite of psilocybin, acts primarily as a partial agonist at serotonin 5-HT₂A receptors, particularly on cortical pyramidal neurons in layers V and VIsupported

Reviews evidence for 5-HT2A as primary site of hallucinogen action. j.bbr.2014.07.016

Psilocin, the active metabolite of psilocybin, acts primarily as a partial agonist at serotonin 5-HT₂A receptors, particularly on cortical pyramidal neurons in layers V and VIsupported

Reviews evidence that indoleamine hallucinogens including psilocybin act primarily through 5-HT2A. j.neuropharm.2011.01.017

Psilocin, the active metabolite of psilocybin, acts primarily as a partial agonist at serotonin 5-HT₂A receptors, particularly on cortical pyramidal neurons in layers V and VIsupported

Reviews 5-HT2A receptor's central role in serotonergic psychedelic effects including psilocybin. 164_2018_107

This 5-HT₂A agonism is the primary and necessary mediator of psychedelic effects, confirmed by three convergent lines of evidence: (1) PET imaging demonstrates that subjective psychedelic intensity correlates directly with 5-HT₂A receptor occupancy and plasma psilocin concentrations; (2) ketanserin, a selective 5-HT₂A antagonist, abolishes psilocybin's perceptual effects; and (3) complete cross-tolerance occurs between psilocybin and other serotonergic hallucinogens (LSD, mescaline) but not with non-hallucinogenic drugs targeting other receptors.supported

PET study: psychedelic effects of psilocybin directly correlate with 5-HT2A receptor occupancy and plasma psilocin levels. Confirms 5-HT2A as primary mediator. s41386-019-0324-9

This 5-HT₂A agonism is the primary and necessary mediator of psychedelic effects, confirmed by three convergent lines of evidence: (1) PET imaging demonstrates that subjective psychedelic intensity correlates directly with 5-HT₂A receptor occupancy and plasma psilocin concentrations; (2) ketanserin, a selective 5-HT₂A antagonist, abolishes psilocybin's perceptual effects; and (3) complete cross-tolerance occurs between psilocybin and other serotonergic hallucinogens (LSD, mescaline) but not with non-hallucinogenic drugs targeting other receptors.supported

Reviews evidence for 5-HT2A as primary site of hallucinogen action; cross-tolerance between psilocybin, LSD, mescaline. j.bbr.2014.07.016

Psilocin also exhibits lower-affinity agonist or partial agonist activity at 5-HT₁A, 5-HT₂C, and other serotonin receptor subtypes, which may modulate the subjective experience — for example, 5-HT₁A activity may contribute anxiolytic tonesupported

Reviews evidence that indoleamine hallucinogens including psilocybin act primarily through 5-HT2A but also engage non-5-HT2 sites. j.neuropharm.2011.01.017

A persistent decrease in hippocampal-to-DMN connectivity lasting weeks after administration has been documented, with the duration of this connectivity change associated with therapeutic response in depression.partially supported

Persistent hippocampal-DMN connectivity decrease lasting weeks. FC changes linked to subjective psychedelic experience. s41586-024-07624-5

A systematic review of 14 studies encompassing 112 healthy human participants provides the following pharmacokinetic profile for psilocin after oral psilocybin administration:supported

Systematic review of 14 psilocybin PK studies (8 lab, 6 clinical; 112 healthy humans). pharmaceutics17040411

Claim in neuroscience — inconclusiveinconclusiveworking →

Claim in neuroscience — inconclusiveinconclusiveworking →

Primary states (psychedelic, dreaming) are characterized by richer repertoires of functional connectivity motifs than normal waking consciousness.supported

Entropic brain theory: psilocybin elevates entropy in brain function including repertoire of functional connectivity motifs. Primary states exhibit criticality. fnhum.2014.00020

After decades of prohibition following placement of psilocybin and psilocin in Schedule I of the 1971 UN Convention on Psychotropic Substances, clinical research accelerated from 2006 onward with landmark trials in treatment-resistant depression, major depressive disorder, and substance use disorderssupported

Phase 2 RCT (COMP360): 25mg, 10mg, 1mg psilocybin in TRD. 25mg superior to 1mg control. nejmoa2206443

After decades of prohibition following placement of psilocybin and psilocin in Schedule I of the 1971 UN Convention on Psychotropic Substances, clinical research accelerated from 2006 onward with landmark trials in treatment-resistant depression, major depressive disorder, and substance use disorderssupported

Phase 2 RCT, 11 US sites. 104 participants (MDD, moderate+). Single 25mg psilocybin vs niacin placebo. jama.2023.14530

After decades of prohibition following placement of psilocybin and psilocin in Schedule I of the 1971 UN Convention on Psychotropic Substances, clinical research accelerated from 2006 onward with landmark trials in treatment-resistant depression, major depressive disorder, and substance use disorderssupported

Systematic review of 16 published studies on psilocybin for AUD, TUD, cocaine, opioid use disorders. j.neubiorev.2025.106163

Psilocin acts as a partial agonist at serotonin 5-HT₂A receptors in cortical pyramidal neurons — the primary mechanism confirmed by PET receptor occupancy data and selective antagonist blockade studiessupported

PET study: psychedelic effects of psilocybin directly correlate with 5-HT2A receptor occupancy and plasma psilocin levels. Confirms 5-HT2A as primary mediator. s41386-019-0324-9

Psilocin acts as a partial agonist at serotonin 5-HT₂A receptors in cortical pyramidal neurons — the primary mechanism confirmed by PET receptor occupancy data and selective antagonist blockade studiessupported

Reviews evidence for 5-HT2A as primary site of hallucinogen action; cross-tolerance between psilocybin, LSD, mescaline; discusses animal behavioral paradigms and clinical neuroimaging evidence. j.bbr.2014.07.016

Oral bioavailability of psilocin is approximately 52.7 ± 20%, with Tmax of 1.8–4 hours, elimination half-life of 1.5–4 hours, and metabolism principally via CYP2D6 and CYP3A4.supported

Psilocin Tmax 1.8–4h; bioavailability 52.7±20%. Primary metabolism by CYP2D6 and CYP3A4. Elimination half-life 1.5–4h. pharmaceutics17040411

The experiential profile spans perceptual intensification, geometric visual phenomena, emotional amplification, enhanced cognitive flexibility, and — at higher doses — ego dissolution and mystical-type experiencessupported

Dose-dependent mystical-type experiences. Sustained personal meaning and spiritual significance at 2-month follow-up. pmid:16826400

Effects and duration vary substantially by preparation method, species, and individual specimen potency; alkaloid content varies up to 11-fold within a single species population.supported

P. semilanceata in Norway: dry weight varied 0.17-1.96% across specimens. pmid:17401967

The primary acute risk is psychological: challenging experiences occur in a dose-dependent manner, with set, setting, and prior psychiatric history as critical modifierssupported

59.1% had no challenging experiences; 8.9% had functional impairment >1 day. Co-use of lithium/mood stabilizers strongly associated with greater difficulty and overall harm risk. j.jad.2023.01.073

Co-administration with lithium or monoamine oxidase inhibitors constitutes a dangerous interactionsupported

MAOI + psilocybin mushrooms associated with hypertensive urgency/emergency in case reports. s40263-025-01256-7

Claim in summary — inconclusiveinconclusiveworking →

Strain-to-strain and specimen-to-specimen potency variability remains the largest unresolved dosing challenge — peer-reviewed HPLC data for individual P. cubensis cultivar fruiting bodies are sparse.supported

Reviews genetic diversity, strain variability, and environmental factors affecting psilocybin/psilocin biosynthesis in P. cubensis strains. jof11020099

Substance use disorder trials have employed doses of 20–40 mg/70 kg.supported

Doses 20-40 mg/70 kg in PAP studies. j.neubiorev.2025.106163

For clinical dose reference: Griffiths et al. used 30 mg/70 kg body-weight-adjusted synthetic psilocybin to occasion full mystical-type experiences; Goodwin et al. used a fixed 25 mg dose in treatment-resistant depression; Raison et al. used 25 mg in major depressive disordersupported

Landmark double-blind RCT. 30 mg/70 kg psilocybin in hallucinogen-naive adults. Dose-dependent mystical-type experiences. pmid:16826400

For clinical dose reference: Griffiths et al. used 30 mg/70 kg body-weight-adjusted synthetic psilocybin to occasion full mystical-type experiences; Goodwin et al. used a fixed 25 mg dose in treatment-resistant depression; Raison et al. used 25 mg in major depressive disordersupported

Phase 2 RCT (COMP360): 25mg, 10mg, 1mg psilocybin in TRD. 25mg superior to 1mg control. nejmoa2206443

For clinical dose reference: Griffiths et al. used 30 mg/70 kg body-weight-adjusted synthetic psilocybin to occasion full mystical-type experiences; Goodwin et al. used a fixed 25 mg dose in treatment-resistant depression; Raison et al. used 25 mg in major depressive disordersupported

Single 25mg psilocybin vs niacin placebo + psychological support. MADRS reduced significantly vs placebo. jama.2023.14530

National Poison Data System (NPDS) data from 2023–2024 document increasing clinical toxicity reports from psychoactive mushroom edibles, with products frequently containing unlisted ingredients and inconsistent formulationssupported

National Poison Data System data on psychoactive mushroom edibles 2023-2024. Unregulated products with often unlisted ingredients and inconsistent formulations. Emerging public health concern. 15563650.2025.2599402

Potency varies enormously across species: P. azurescens is approximately 2–4 times more potent per gram than P. cubensis, while P. semilanceata varies up to 11-fold within a single populationpartially supported

P. semilanceata in Norway: dry weight varied 0.17-1.96% across specimens. pmid:17401967

Mushroom-weight dose ranges represent cross-referencing of clinical synthetic psilocybin data against published species potency datasupported

30 mg/70 kg psilocybin in hallucinogen-naive adults. Dose-dependent mystical-type experiences. pmid:16826400

Mushroom-weight dose ranges represent cross-referencing of clinical synthetic psilocybin data against published species potency datasupported

Phase 2 RCT (COMP360): 25mg, 10mg, 1mg psilocybin in TRD. nejmoa2206443

Mushroom-weight dose ranges represent cross-referencing of clinical synthetic psilocybin data against published species potency datasupported

Single 25mg psilocybin vs niacin placebo. jama.2023.14530

Mushroom-weight dose ranges represent cross-referencing of clinical synthetic psilocybin data against published species potency datasupported

P. semilanceata in Norway: psilocybin the major hallucinogenic constituent; dry weight varied 0.17-1.96% across specimens. pmid:17401967

Psilocin (4-hydroxy-N,N-dimethyltryptamine; C₁₂H₁₆N₂O; MW 204.27 g/mol) is the pharmacologically active form, directly engaging 5-HT₂A and other serotonin receptor subtypessupported

Reviews evidence for 5-HT2A as primary site of hallucinogen action; discusses animal behavioral paradigms and clinical neuroimaging evidence. j.bbr.2014.07.016

Aeruginascin (N,N,N-trimethyl-4-phosphoryloxytryptammonium; MW ~299 g/mol) is a quaternary ammonium phosphoryl tryptamine detected in Psilocybe tissue via MALDI-FT ICR MS alongside psilocybin, psilocin, and baeocystinsupported

MALDI-FT ICR MS imaging of psilocybin, psilocin, baeocystin, tryptophan, tryptamine, and aeruginascin in Psilocybe tissue sections. Aeruginascin identified alongside other alkaloids. s00216-022-04467-9

One HPLC study found the Cambodian strain mycelium contained 20.78 mg psilocybin per 100 g dry weight (0.021%) — substantially lower than fruiting body concentrationssupported

Cambodian strain contained psilocybin at 20.78 mg per 100 g dry weight (equivalent to 0.021% dry weight — much lower in mycelium vs fruiting bodies). jpp.2026.1.07

Claim in alkaloid-profile — inconclusiveinconclusiveworking →

Claim in alkaloid-profile — inconclusiveinconclusiveworking →

Published peer-reviewed data comparing fruiting body alkaloid content across named P. cubensis strains remain sparse due to regulatory constraints on cultivation for analytical purposes.supported

Reviews genetic diversity, strain variability, and environmental factors affecting psilocybin/psilocin biosynthesis in P. cubensis strains. jof11020099

Potency varies not only by species and strain but by individual specimen size (smaller specimens of P. semilanceata contain higher concentrations per unit dry weight), growing conditions, substrate composition, and post-harvest handling.supported

P. semilanceata in Norway: psilocybin the major hallucinogenic constituent; dry weight varied 0.17-1.96% across specimens. Highest concentration in smaller mushrooms. pmid:17401967

The landmark study by Griffiths and colleagues in 2006 demonstrated that psilocybin (30 mg/70 kg) could occasion mystical-type experiences with sustained personal meaning and behavioral change in a double-blind crossover designsupported

Landmark double-blind RCT. 30 mg/70 kg psilocybin in hallucinogen-naive adults. Sustained personal meaning and spiritual significance at 2-month follow-up. Community observers confirmed positive behavioral changes. pmid:16826400

Raison et al. (2023): single 25 mg dose for MDD published in JAMAsupported

Phase 2 RCT, 11 US sites. 104 participants (MDD, moderate+). Single 25mg psilocybin vs niacin placebo. jama.2023.14530

Claim in history — not_supportednot supportedworking →

Claim in history — inconclusiveinconclusiveworking →

The Heffter Research Institute, founded in 1993, provided early infrastructure and funding for renewed psilocybin clinical researchsupported

Describes the Heffter Research Institute's history; first OCD psilocybin study; UCLA study in end-stage cancer; NYU trial; Johns Hopkins smoking cessation, anxiety/depression in cancer, and long-term meditators studies. pmid:24830182

Davis et al. (2020): psilocybin-assisted therapy for major depressive disorder — 71% response, 54% remission at 4 weekssupported

N=27. 71% response and 54% remission at 4 weeks. jamapsychiatry.2020.3285

The designation "psilocybin mushrooms" is a pharmacological rather than strictly monophyletic grouping — psilocybin-producing species also occur in Panaeolus, Gymnopilus, and Pluteus.supported

Review of psilocybin-containing Panaeolus species: global distribution, species diversity, DNA sequence data, psychedelic potential. j.heliyon.2023.e16338

P. cubensis (Earle) Singer — pantropical distribution; grows on dung in humid subtropical regions (Americas, Southeast Asia, Africa). The most widely cultivated species globally, grown on sterilized grain, straw, or manure substrates.supported

Covers cultivation techniques including submerged fermentation of mycelium and analytical methodologies for compound quantification. jof11020099

DNA barcoding of the internal transcribed spacer (ITS) region provides definitive species-level identification when morphological assessment is ambiguous.supported

ITS sequencing, SEM, and mass spectrometry identification of Psilocybe cubensis from mycelia. HRM and ITS confirmed species identity. j.scijus.2018.08.005

Set and setting exert an unusually large influence on outcome valence: the same dose in the same individual can produce profoundly positive or acutely distressing experiences depending on psychological preparation and environmental context.supported

Non-pharmacological variables (personality, pre-drug state) significantly contribute. Identifies set and setting factors for pleasant vs anxious responses. journal.pone.0030800

Claim in legal-status — inconclusiveinconclusiveworking →