generation run 2026-05-14
84 min completedmodel pipeline-v5plan not recordedrun/d0fcf526…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
- safety_data_unverified
- safety_data_unverified
- safety_data_unverified
- sparse_evidence
- sparse_evidence
- sparse_evidence
- sparse_evidence
- sparse_evidence
- contaminant_data_absent
Reproduce
- inputs
- 32 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
- streams
- none — agent transcripts are persisted from 2026-09 onward
22 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubChem | psilocybin | 1 | 1 | Primary active alkaloid in Psilocybe cubensis |
| 2 | ClinicalTrials.gov | psilocybin Psilocybe mushroom | 14 | 6 | Most relevant active/completed trials; NCT06898606 specifically uses whole Psilocybe cubensis mushrooms |
| 3 | PubMed | psilocybin pharmacology mechanism serotonin receptor | 15 | 5 | Mechanism and neuroplasticity papers; selected strongest reviews and most relevant pharmacology papers |
| 4 | OpenAlex | psilocybin therapeutic depression anxiety clinical trial | 10 | 7 | Most-cited landmark clinical trials and theoretical frameworks for psilocybin |
| 5 | PubChem | baeocystin | 1 | 1 | Minor alkaloid co-present in Psilocybe cubensis |
| 6 | PubMed | psilocybin pharmacokinetics bioavailability human plasma | 2 | 2 | Definitive pharmacokinetics data for the substance |
| 7 | PubMed | psilocybin dose response effects subjective human study | 10 | 3 | Safety data, dose information, and adverse events |
| 8 | PubChem | psilocin | 1 | 1 | Active metabolite of psilocybin; responsible for psychoactive effects |
| 9 | PubChem | norbaeocystin | 1 | 1 | Minor alkaloid co-present in Psilocybe species |
| 10 | OpenAlex | psilocybin psilocin magic mushroom alkaloid quantification HPLC | 10 | 3 | Critical for alkaloid profile section; beta-carboline finding is unique and important |
| 11 | OpenAlex | Psilocybe cubensis taxonomy botany alkaloids | 10 | 7 | All highly relevant to botanical identity, alkaloid profile, and ethnobotany |
| 12 | WebSearch | psilocybin legal status UK Germany Australia Netherlands international | 10 | 5 | Jurisdiction-specific legal status needed for article |
| 13 | PubMed | psilocybin HPPD hallucinogen persisting perception disorder psychosis | 3 | 2 | HPPD adverse effect data; risk characterization |
| 14 | ClinicalTrials.gov | psilocybin Psilocybe mushroom clinical trials | 14 | 5 | Active and completed trials most relevant to P. cubensis and psilocybin |
| 15 | PubMed | psilocybin drug test urine detection immunoassay | 2 | 2 | Drug test detection data |
| 16 | PubMed | PMID 39997393 fetch | 1 | 1 | Specifically addresses P. cubensis strain variability and cultivation |
| 17 | PubMed | PMID 18593734 Johnson 2008 hallucinogen safety guidelines | 1 | 1 | Foundational safety guidelines for psilocybin research |
| 18 | WebSearch | psilocybin mushroom Australia TGA rescheduling 2023 | 10 | 3 | Australia legal status data |
| 19 | WebSearch | psilocybin legal status Schedule I DEA United States federal law psilocybe mushrooms | 10 | 3 | Critical legal context for the article |
| 20 | PubMed | PMID 16826400 Griffiths 2006 mystical experiences | 1 | 1 | Landmark foundational study establishing subjective effects at moderate-high doses |
| 21 | OpenAlex | psilocybin mystical experience personality openness Griffiths | 8 | 3 | Key papers on subjective effects, personality changes, and therapeutic overview |
| 22 | PubMed | psilocybin fMRI brain connectivity neuroimaging | 8 | 2 | Neural mechanism data; DMN, hippocampus, persistence of effects |
74 claims by section — every cited sentence, checked against its source
safety31 · 19 ok
Claim in safety — inconclusiveinconclusiveworking →
No human fatalities from psilocybin toxicity alone have been documented in the peer-reviewed literaturesupported
Hallucinogens are relatively safe physiologically and not drugs of dependence. 0269881108093587
Claim in safety — inconclusiveinconclusiveworking →
The largest Phase 2 trial (233 participants with treatment-resistant depression) reported adverse events in 77% of participants; the most common were headache, nausea, and dizzinesssupported
Phase 2 double-blind, 233 TRD patients. Adverse events 77%: headache, nausea, dizziness. nejmoa2206443
A Phase 2 RCT of 25 mg psilocybin for major depressive disorder reported no serious treatment-emergent adverse events but a higher overall rate of adverse events versus niacin placebo.supported
No serious AEs; higher rate overall AEs vs niacin. jama.2023.14530
A molecularly confirmed case series of Psilocybe keralensis poisoning documented myocardial injury, though this species differs from P. cubensissupported
Cluster of Psilocybe keralensis poisonings in Chengdu, China. Unique clinical features including cardiovascular complications. Molecularly confirmed. 15563650.2025.2552438
Claim in safety — inconclusiveinconclusiveworking →
Standard workplace immunoassay urine drug screens do not reliably detect psilocin, with cross-reactivity of approximately 1.3% on amphetamine/methamphetamine assayssupported
Psilocin has low cross-reactivity (~1.3%) on amphetamine/methamphetamine immunoassays. Standard routine urine drug testing does not detect psilocin/psilocybin. bs.acc.2016.07.004
Standard workplace immunoassay urine drug screens do not reliably detect psilocin, with cross-reactivity of approximately 1.3% on amphetamine/methamphetamine assayssupported
Psilocin identified in urine by GC-MS after positive amphetamine/methamphetamine immunoassay (1.3% cross-reactivity). pmid:16839473
Claim in safety — inconclusiveinconclusiveworking →
Ehrlich reagent testing (DMAB) produces a purple/violet reaction indicating indole presence but does not distinguish psilocybin from all synthetic indole imposters; definitive identification requires GC-MS or LC-MS/MS.partially supported
GC-MS or LC-MS/MS required for confirmation. bs.acc.2016.07.004
The most common adverse psychological event is the acute anxiety reaction — an overwhelming experience characterized by intense anxiety, fear, paranoia, panic, and dysphoric confusionsupported
Primary risks: overwhelming distress ('bad trip'), rare prolonged psychosis. 0269881108093587
This risk is dose-dependent and context-dependent, mitigated by appropriate set, setting, and interpersonal supportsupported
Clear intentions, positive set, higher doses all promote experience quality. fphar.2018.00897
In the Carhart-Harris et al. (2016) open-label TRD study, transient anxiety was reported by all 12 participants during drug onset, with transient confusion or thought disorder in 9 of 12, and mild nausea in 4 of 12.supported
Adverse reactions: transient anxiety (all), confusion/thought disorder (9), nausea (4), headache (4). s2215-0366(16)30065-7
This constitutes the principal screening contraindication in all clinical research protocols.supported
Safeguards: exclude personal/family history of psychotic disorders. 0269881108093587
Psilocybin and LSD are the most commonly reported precipitantssupported
Notes LSD and psilocybin as most common HPPD-precipitating substances. pha0000597
HPPD has been documented in adolescents and adults, though precise prevalence estimates remain unavailable.supported
Case report of HPPD in a 16-year-old, highlighting pediatric presentation, diagnosis, and treatment. pb.4525
Claim in safety — inconclusiveinconclusiveworking →
Psilocybin produces no physical dependence and no clinically recognized withdrawal syndromesupported
Hallucinogens are relatively safe physiologically and not drugs of dependence. 0269881108093587
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
The mechanism involves dual MAO-A inhibition: exogenous MAOIs combined with endogenous β-carboline MAO inhibitors in the mushroom matrix severely impair serotonin metabolism, potentiating both serotonergic and sympathomimetic effectspartially supported
Magic mushrooms simultaneously produce psilocybin and β-carboline MAO inhibitors from L-tryptophan. β-carbolines are neuroactive and interfere with psilocybin degradation. chem.201904363
A post-hoc analysis of 233 treatment-resistant depression patients found that antidepressant discontinuation prior to psilocybin treatment did not significantly affect clinical outcomessupported
Post-hoc analysis of 233 TRD patients (COMP360 trial). Antidepressant discontinuation before psilocybin did not compromise efficacy or subjective psychedelic experience. j.jpsychires.2024.10.009
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Personal or family history of psychotic disorders (schizophrenia, schizoaffective disorder, bipolar I with psychotic features): psilocybin may precipitate or exacerbate psychosis. This is the primary exclusion criterion in all clinical research protocols.supported
Safeguards: exclude personal/family history of psychotic disorders... Primary risks: overwhelming distress ('bad trip'), rare prolonged psychosis. 0269881108093587
Active suicidal ideation: exclusion criterion in clinical trials. Suicidal ideation was reported across all dose groups (including 1 mg control) in a TRD population, consistent with the underlying condition rather than a drug-specific effect.supported
Suicidal ideation in all groups. nejmoa2206443
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Adolescent and pediatric populations: No clinical trials have been conducted in minors; a case report of HPPD in a 16-year-old documents vulnerability in this population.supported
Case report of HPPD in a 16-year-old, highlighting pediatric presentation, diagnosis, and treatment. pb.4525
summary11 · 6 ok
Claim in summary — inconclusiveinconclusiveworking →
Dried fruiting bodies consumed orally in several preparation forms produce psychedelic effects lasting 4–8 hours.supported
Onset 30-60 min, peak 2-3h, subsided ≥6h. s2215-0366(16)30065-7
Claim in summary — inconclusiveinconclusiveworking →
Schedule I classification in 1970 halted research for decades, a landmark 2006 controlled study re-established clinical investigationsupported
Landmark double-blind RCT in hallucinogen-naive healthy adults. 30 mg/70kg psilocybin vs methylphenidate control. pmid:16826400
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Oral bioavailability is approximately 52.7%, with psilocin Tmax of 1.8–4 hours and an elimination half-life of 1.5–4 hours; metabolism proceeds primarily via CYP2D6 and CYP3A4.partially supported
Absolute bioavailability 52.7±20%. Oral 10-20mg: psilocin Cmax 8.2±2.8 ng/mL at 105±37 min. pmid:9204776
Effects and duration vary substantially by preparation method, dose, individual sensitivity, and the well-documented influence of set and setting.supported
Clear intentions, positive set, higher doses all promote experience quality. Baseline traits have strongest effect on well-being change. fphar.2018.00897
Psilocybin has low acute physiological toxicity; no human fatalities from psilocybin toxicity alone are documented in the peer-reviewed literaturesupported
Hallucinogens are relatively safe physiologically and not drugs of dependence. 0269881108093587
Concurrent monoamine oxidase inhibitor use poses hypertensive emergency risk, amplified by endogenous β-carboline MAO inhibitors present in the mushroom matrixpartially supported
Magic mushrooms simultaneously produce psilocybin and β-carboline MAO inhibitors from L-tryptophan. β-carbolines are neuroactive and interfere with psilocybin degradation. chem.201904363
Claim in summary — inconclusiveinconclusiveworking →
neuroscience10 · 6 ok
Cmax: 8.2 ± 2.8 ng/mL at oral doses of 10–20 mg psilocybin.supported
Oral 10-20mg: psilocin Cmax 8.2±2.8 ng/mL at 105±37 min. pmid:9204776
Intravenous administration of 1 mg psilocybin produces psilocin Cmax of 12.9 ± 5.6 ng/mL at 1.9 ± 1.0 minutes, confirming rapid dephosphorylation in blood.supported
IV 1mg: psilocin Cmax 12.9±5.6 ng/mL at 1.9±1.0 min. pmid:9204776
Claim in neuroscience — inconclusiveinconclusiveworking →
5-HT₁A agonism — contributes to long-term synaptic depression via enhanced GABAergic tone; recent evidence demonstrates 5-HT₁A-mediated, 5-HT₂A-independent long-term depression in the prelimbic cortex.supported
Psilocin produces 5-HT2A-independent LTD in prelimbic cortex via enhanced GABAergic tone and partially via 5-HT1A and TrkB receptors. j.neuropharm.2026.110854
Claim in neuroscience — inconclusiveinconclusiveworking →
5-HT₂B — at sub-psychedelic doses, psilocin demonstrates metabolic effects (weight and liver steatosis reduction in mice) via hepatic 5-HT₂B antagonism, a mechanism distinct from its central psychedelic activity.supported
Sub-psychedelic psilocybin (0.05mg/kg) reduces obesity, liver steatosis, hyperglycemia in mice via hepatic 5-HT2B antagonism, not 5-HT2A. No CNS effects at this dose. j.phrs.2025.108080
Claim in neuroscience — inconclusiveinconclusiveworking →
A persistent decrease in hippocampal-DMN connectivity lasted for three weeks post-session — hypothesized as a neuroanatomical correlate of psilocybin's pro-plasticity and therapeutic effects.supported
Persistent hippocampal-DMN connectivity decrease lasting weeks. s41586-024-07624-5
Claim in neuroscience — inconclusiveinconclusiveworking →
This may extend the effective half-life of psilocin from whole-mushroom preparations relative to synthetic psilocybinsupported
β-carbolines are neuroactive and interfere with psilocybin degradation. chem.201904363
alkaloid-profile6 · 3 ok
Claim in alkaloid-profile — inconclusiveinconclusiveworking →
Claim in alkaloid-profile — inconclusiveinconclusiveworking →
The largest published systematic alkaloid quantification study analyzed 226 fruiting bodies from 82 collections across 7 genera using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). Psilocybe species exhibited the highest psilocybin and psilocin concentrations among all genera testedsupported
UHPLC-MS/MS quantification of psilocybin, psilocin, baeocystin, norbaeocystin, and aeruginascin in 226 fruiting bodies of 82 collections from 7 genera. Highest psilocybin concentrations in Psilocybe species. ijms232214068
Claim in alkaloid-profile — inconclusiveinconclusiveworking →
Psilocybe mushrooms simultaneously produce a cocktail of β-carboline monoamine oxidase inhibitors — including harmane and norharman — as biosynthetic products of L-tryptophan metabolismsupported
Magic mushrooms simultaneously produce psilocybin and β-carboline MAO inhibitors from L-tryptophan. chem.201904363
A preclinical comparison of psychedelic mushroom extract (PME) versus chemically synthesized psilocybin in mice found that PME produced similar acute head-twitch responses but significantly more potent and prolonged synaptic plasticity markers (GAP43, synaptophysin) in frontal cortex, hippocampus, and amygdala at 11 days post-treatmentsupported
PME vs synthetic psilocybin in mice. PME more potent and prolonged synaptic plasticity. s41380-024-02477-w
botanical-overview5 · 2 ok
Claim in botanical-overview — inconclusiveinconclusiveworking →
The psilocybin biosynthetic gene cluster first arose within Psilocybe, with 4–5 probable horizontal gene transfers to other mushroom genera between 40 and 9 mya.partially supported
Psilocybin biosynthesis first arose in Psilocybe with 4-5 horizontal transfers. pnas.2311245121
Claim in botanical-overview — inconclusiveinconclusiveworking →
Claim in botanical-overview — inconclusiveinconclusiveworking →
Both genetics and environmental cultivation conditions — substrate composition, temperature, humidity, light cycle — significantly affect alkaloid biosynthesissupported
Reviews genetic diversity, strain variability, and environmental factors affecting psilocybin/psilocin biosynthesis in P. cubensis strains. jof11020099
preparations5 · 4 ok
Claim in preparations — inconclusiveinconclusiveworking →
Clinical reference points using synthetic psilocybin: 10 mg produces detectable effects at 30–60 minutes; 25 mg is the primary therapeutic dose in Phase 2 trials; 30 mg/70 kg reliably occasions mystical-type experiences in healthy volunteers.supported
12 TRD patients; 10mg and 25mg oral. Onset 30-60 min, peak 2-3h, subsided ≥6h. s2215-0366(16)30065-7
Clinical reference points using synthetic psilocybin: 10 mg produces detectable effects at 30–60 minutes; 25 mg is the primary therapeutic dose in Phase 2 trials; 30 mg/70 kg reliably occasions mystical-type experiences in healthy volunteers.supported
Phase 2 double-blind, 233 TRD patients. 25mg significantly reduced MADRS vs 1mg control. nejmoa2206443
Clinical reference points using synthetic psilocybin: 10 mg produces detectable effects at 30–60 minutes; 25 mg is the primary therapeutic dose in Phase 2 trials; 30 mg/70 kg reliably occasions mystical-type experiences in healthy volunteers.supported
30 mg/70kg psilocybin vs methylphenidate control. Substantial mystical experiences. pmid:16826400
Onset: 20–60 minutes. Peak: 2–3 hours. Total duration: 4–8 hours.supported
Onset 30-60 min, peak 2-3h, subsided ≥6h. s2215-0366(16)30065-7
history4 · 1 ok
The landmark Griffiths et al. (2006) double-blind study at Johns Hopkins demonstrated that psilocybin (30 mg/70 kg) reliably occasioned mystical-type experiences in healthy volunteers, with 67% rating the session among their five most personally meaningful life experiences at two-month follow-upsupported
Landmark double-blind RCT in hallucinogen-naive healthy adults. 30 mg/70kg psilocybin vs methylphenidate control. Substantial mystical experiences; 67% rated among top 5 most meaningful life experiences at 2-month follow-up. pmid:16826400
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
effects-overview2 · 2 ok
The experiential character of Psilocybe cubensis is shaped primarily by dose, preparation method, and the psychosocial context of consumption — set and setting exert an influence on experience quality that rivals or exceeds that of dose alonesupported
Clear intentions, positive set, higher doses all promote experience quality. Baseline traits have strongest effect on well-being change. fphar.2018.00897
The mushroom matrix delivers a cocktail of tryptamine alkaloids alongside β-carboline MAO inhibitors, producing a pharmacological milieu distinct from synthetic psilocybin; whether this translates to a meaningfully different subjective profile in humans remains an open question supported only by preclinical evidencesupported
PME vs synthetic psilocybin in mice. PME more potent and prolonged synaptic plasticity. Differential frontal cortex metabolomics suggests full-spectrum entourage effects. s41380-024-02477-w