generation run 2026-04-24
71 min completedmodel pipeline-v5plan not recordedrun/5df26e00…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
none raised on this run
Reproduce
- inputs
- 21 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
16 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | OpenAlex | mescaline peyote history discovery Heffter Lewin isolation | 3 | 1 | Review with historical context on peyote and mescaline |
| 2 | PubMed | mescaline human pharmacokinetics metabolism half-life | 2 | 2 | First modern controlled PK/PD data for mescaline in humans |
| 3 | PubMed | mescaline receptor binding affinity pharmacology serotonin dopamine | 3 | — | — |
| 4 | OpenAlex | mescaline 5-HT2A receptor agonist binding affinity Ki | 2 | 1 | Primary receptor binding affinity data source for mescaline |
| 5 | PubMed | mescaline peyote psychedelic effects humans controlled study | 10 | 2 | Key comparative and systematic review papers |
| 6 | ClinicalTrials.gov | mescaline | 7 | 2 | Directly relevant completed Phase 1 trials on mescaline |
| 7 | PubMed | mescaline metabolism MAO oxidation | 4 | 2 | Historical metabolism data - MAO involvement |
| 8 | PubChem | mescaline | 1 | 1 | Verified all chemical identity data for mescaline |
| 9 | OpenAlex | Klaiber 2024 referenced works | 5 | 2 | Historical papers on mescaline in psychiatry and tissue distribution |
| 10 | WebSearch | mescaline legal status Schedule I DEA United States UK Canada Australia international | 10 | 1 | Legal status not available via academic APIs |
| 11 | OpenAlex | mescaline 5-HT2A receptor agonist binding affinity Ki NIMH PDSP | 2 | 1 | Best available receptor affinity data |
| 12 | PubMed | mescaline peyote psychedelic effects humans controlled study | 10 | 2 | Direct mescaline human studies |
| 13 | ClinicalTrials.gov | mescaline | 7 | 2 | Both directly relevant completed Phase 1 trials |
| 14 | Crossref | DOI verification for key papers | 3 | 3 | Confirmed validity of primary RCT papers |
| 15 | PubMed | Nichols psychedelics pharmacological review 2016 serotonin receptor | 2 | 2 | Comprehensive pharmacological reviews with mescaline receptor binding data |
| 16 | OpenAlex | peyote Native American Church mescaline legal exemption | 8 | 1 | Peyote legal history and scheduling narrative |
86 claims by section — every cited sentence, checked against its source
safety22 · 12 ok
Claim in safety — inconclusiveinconclusiveworking →
Shaw et al. (2026), in the first systematic review, reported hypertension, headache, nausea, and vomiting as common adverse effectssupported
Common AEs: hypertension, headache, nausea, vomiting. ijms27073081
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Hardman et al. (1973) examined mescaline toxicity across five laboratory species; Davis et al. (1978) studied acute toxicity in rodents, dogs, and monkeyssupported
Toxicity and behavioral data for mescaline and analogs in five species of laboratory animals. pmid:4197635
Hardman et al. (1973) examined mescaline toxicity across five laboratory species; Davis et al. (1978) studied acute toxicity in rodents, dogs, and monkeyssupported
Acute toxicity and gross behavioral effects of mescaline in rodents, dogs, and monkeys. pmid:99845
Mescaline is listed among substances associated with hallucinogen-persisting perception disorder (HPPD), characterized by visual disturbances that persist or recur after resolution of acute effectssupported
HPPD associated with LSD, psilocybin, mescaline, cannabis, MDMA. Symptoms include geometric pseudo-hallucinations, halos, afterimages. fpsyt.2017.00240
Hoch (1951) observed exacerbation of symptoms in patients with latent schizophrenia following intravenous mescalinesupported
Intravenous synthetic mescaline produced psychosis-like effects in normal volunteers and exacerbated schizophrenic symptoms. pmid:14819349
Claim in safety — not_supportednot supportedworking →
Acute challenging psychological experiences — anxiety, fear, confusion, and difficult emotional states — occur at variable frequency and are considered part of the expected risk profile of serotonergic psychedelics in clinical settings.supported
Acute challenging experiences may be therapeutically meaningful. AEs poorly defined and probably underreported. 02698811221116926
A population-level study of 130,152 US adults found no association between lifetime classical psychedelic use (LSD, psilocybin, mescaline) and increased rates of mental health problems, suicidality, or psychological distress.partially supported
LSD, psilocybin, mescaline regarded as non-addictive. Over 30 million US residents have used these substances. No increased mental health problems found. journal.pone.0063972
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
No compulsive use patterns, withdrawal syndrome, or dependence formation have been documentedsupported
Generally physiologically safe, non-addictive. pr.115.011478
No compulsive use patterns, withdrawal syndrome, or dependence formation have been documentedsupported
LSD, psilocybin, mescaline regarded as non-addictive. journal.pone.0063972
The most dangerous pharmacodynamic interactions involve agents that increase serotonergic tone or inhibit monoamine oxidase. Alpha-methyltryptamine (αMT), which functions as both a monoamine releaser and an MAO inhibitor, creates risk of severe serotonin syndrome when combined with a serotonergic agonist such as mescaline — a potentially lethal combination. Tramadol, a weak serotonin-norepinephrine reuptake inhibitor and mu-opioid agonist, poses serotonin syndrome risk and additionally lowers the seizure threshold.supported
Review of tramadol and serotonergic drug interactions leading to serotonin syndrome. Prescribing restrictions may be warranted. 0897190013504957
Chronic SSRI administration downregulates 5-HT₂A receptors and substantially attenuates or eliminates psychedelic effectssupported
Chronic SSRI administration attenuates LSD subjective effects, likely via 5-HT2A receptor downregulation. 0893-133x(95)00145-4
Claim in safety — not_supportednot supportedworking →
Psychotic disorders and family history of psychosis represent absolute contraindications, supported by historical evidence of psychosis exacerbation.supported
Intravenous synthetic mescaline produced psychosis-like effects in normal volunteers and exacerbated schizophrenic symptoms. pmid:14819349
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — not_supportednot supportedworking →
summary15 · 12 ok
Among classical psychedelics, mescaline occupies the low-potency end of the spectrum — active oral doses range from 200–500 mg of the hydrochloride salt, roughly 2,000-fold the mass required for LSD — with a correspondingly long duration of 6–14 hours depending on dose.partially supported
effect duration 6.4–14h. Dose-proportional PK s41398-024-03116-2
Claim in summary — inconclusiveinconclusiveworking →
After decades of use in psychotomimetic research and psychedelic-assisted psychotherapy, mescaline was placed in Schedule I under both the US Controlled Substances Act (1970) and the UN Convention on Psychotropic Substances (1971)partially supported
Classical psychedelics including mescaline used extensively in psychiatry before Schedule I classification in 1967. j.neuropharm.2017.12.040
Principal psychological risks include acute anxiety, possible psychosis precipitation in predisposed individuals, and rare hallucinogen-persisting perception disorder (HPPD)partially supported
HPPD associated with LSD, psilocybin, mescaline, cannabis, MDMA. Symptoms include geometric pseudo-hallucinations, halos, afterimages. fpsyt.2017.00240
The first modern dose-finding randomized controlled trials were published in 2023–2024 by the Liechti group at University Hospital Basel, establishing pharmacokinetic parameters and confirming the 5-HT₂A mechanism in humans.supported
Dose-proportional PK, Tmax ~2h, t½ ~3.5h, effect duration 6.4–14h. Ketanserin attenuated effects, confirming 5-HT2A primary mechanism. s41398-024-03116-2
The first modern dose-finding randomized controlled trials were published in 2023–2024 by the Liechti group at University Hospital Basel, establishing pharmacokinetic parameters and confirming the 5-HT₂A mechanism in humans.partially supported
RCT comparing mescaline 300/500mg, LSD 100μg, psilocybin 20mg in 32 healthy participants. s41386-023-01607-2
Mescaline acts primarily as an agonist at serotonin 5-HT₂A receptors, with secondary activity at 5-HT₂C and alpha-1 adrenergic sitessupported
Includes Ki data for mescaline at 5-HT2A, 5-HT2C, and other receptors. Phenylalkylamines interact with 42 of 49 sites. journal.pone.0009019
Co-administration of the selective 5-HT₂A antagonist ketanserin (40 mg) attenuated mescaline's subjective effects to levels comparable to one-quarter the administered dose, confirming 5-HT₂A as the principal mediatorpartially supported
800 mg + ketanserin. Ketanserin attenuated effects, confirming 5-HT2A primary mechanism. s41398-024-03116-2
Claim in summary — inconclusiveinconclusiveworking →
At equipotent doses, mescaline produces altered states of consciousness qualitatively indistinguishable from those induced by LSD and psilocybin on validated psychometric scales — the primary differences are pharmacokinetic rather than phenomenologicalsupported
Subjective effects comparable at equipotent doses. Mescaline had longest duration (mean 11.1h vs LSD 8.2h vs psilocybin 4.9h). s41386-023-01607-2
Mescaline uniquely elevates plasma oxytocin, potentially underlying reported empathogenic qualitiespartially supported
Mescaline and LSD enhanced oxytocin; no BDNF changes. s41386-023-01607-2
Claim in summary — inconclusiveinconclusiveworking →
Mescaline is non-addictive: rapid tachyphylaxis via 5-HT₂A receptor downregulation limits repeated use, and no compulsive dosing, withdrawal syndrome, or dependence formation has been documentedsupported
Generally physiologically safe, non-addictive. pr.115.011478
Mescaline is non-addictive: rapid tachyphylaxis via 5-HT₂A receptor downregulation limits repeated use, and no compulsive dosing, withdrawal syndrome, or dependence formation has been documentedsupported
LSD, psilocybin, mescaline regarded as non-addictive. journal.pone.0063972
Population-level data show no increased mental health problems associated with classical psychedelic usesupported
No increased mental health problems found. journal.pone.0063972
pharmacology14 · 10 ok
This was confirmed in humans by Klaiber et al. (2024): co-administration of the selective 5-HT₂A antagonist ketanserin (40 mg) with mescaline 800 mg attenuated and shortened subjective effects to levels comparable to 100–200 mg mescaline alone. 5-HT₂A activation triggers Gq-protein-mediated phospholipase C signaling, producing inositol trisphosphate (IP₃) generation and calcium release from the endoplasmic reticulumpartially supported
800 mg + ketanserin. Ketanserin attenuated effects, confirming 5-HT2A primary mechanism. s41398-024-03116-2
This was confirmed in humans by Klaiber et al. (2024): co-administration of the selective 5-HT₂A antagonist ketanserin (40 mg) with mescaline 800 mg attenuated and shortened subjective effects to levels comparable to 100–200 mg mescaline alone. 5-HT₂A activation triggers Gq-protein-mediated phospholipase C signaling, producing inositol trisphosphate (IP₃) generation and calcium release from the endoplasmic reticulumsupported
Overview of peyote alkaloids, mescaline mechanism via 5-HT2A receptor and calcium release from ER. molecules28247942
The relevant 5-HT₂A receptors are concentrated on apical dendrites of neocortical pyramidal cells in cortical layer V — the canonical site of psychedelic action.supported
Agonists/partial agonists at 5-HT2A receptors on neocortical pyramidal cells layer V. pr.115.011478
Secondary targets include 5-HT₂C and alpha-1 adrenergic receptorssupported
Includes Ki data for mescaline at 5-HT2A, 5-HT2C, and other receptors. Phenylalkylamines interact with 42 of 49 sites. journal.pone.0009019
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
A conformationally restricted mescaline analog demonstrated 3-fold higher 5-HT₂A affinity and 5-fold higher potency than mescaline with equivalent efficacy, further confirming mescaline's relatively modest receptor binding.partially supported
Conformationally restricted mescaline analogue with 3-fold higher 5-HT2A affinity/potency than mescaline. pmid:16821786
Pharmacokinetics are dose-proportional across the 100–800 mg range, with no ceiling effect on subjective responsesupported
Dose-proportional PK, Tmax ~2h, t½ ~3.5h, effect duration 6.4–14h. s41398-024-03116-2
Subjective effect duration ranges from 6.4 hours at 100 mg to 14 hours at 800 mg.supported
effect duration 6.4–14h. s41398-024-03116-2
The extended subjective duration relative to the 3.5-hour plasma half-life is explained by slow oral absorption (prolonged Tmax) rather than extended receptor occupancy — a pattern confirmed by direct pharmacokinetic comparison with LSD, which has a similar plasma half-life but shorter Tmax and shorter effect duration at equivalent subjective intensity.partially supported
Mescaline had longest duration (mean 11.1h vs LSD 8.2h vs psilocybin 4.9h). s41386-023-01607-2
The primary metabolic pathway is MAO-mediated oxidative deamination, demonstrated in animal CNS tissue and confirmed by MAO inhibitor studies in rabbitssupported
Oxidative deamination of mescaline by mouse brain regions in vitro, demonstrating regional CNS MAO metabolism. pmid:5163157
The primary metabolic pathway is MAO-mediated oxidative deamination, demonstrated in animal CNS tissue and confirmed by MAO inhibitor studies in rabbitssupported
MAO inhibitor aminoacetonitrile affected mescaline metabolism, demonstrating MAO involvement in mescaline oxidative deamination. pmid:1168468
Claim in pharmacology — inconclusiveinconclusiveworking →
Claim in pharmacology — inconclusiveinconclusiveworking →
history8 · 5 ok
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
From the 1940s through the 1960s, mescaline and LSD were used extensively in psychiatry as psychotherapy adjuncts, with preliminary studies suggesting efficacy in anxiety and alcoholismsupported
Classical psychedelics including mescaline used extensively in psychiatry before Schedule I classification in 1967. j.neuropharm.2017.12.040
Mescaline was placed in Schedule I under the United States Controlled Substances Act of 1970 and subsequently in Schedule I of the UN Convention on Psychotropic Substances in 1971partially supported
Classical psychedelics including mescaline used extensively in psychiatry before Schedule I classification in 1967. j.neuropharm.2017.12.040
The Liechti group at University Hospital Basel conducted the first modern dose-finding randomized controlled trials for mescaline (NCT04849013 and NCT04227756), published as Klaiber et al. (2024) and Ley et al. (2023)supported
Randomized, double-blind, placebo-controlled crossover study in 16 healthy subjects receiving mescaline (100–800 mg) and 800 mg + ketanserin. s41398-024-03116-2
Shaw et al. (2026) conducted the first systematic review of mescaline's use for psychiatric disorders, concluding that existing literature is limited and of highly variable quality.supported
Systematic review of 66 studies (10 suitable for analysis). Limited quality evidence. ijms27073081
Peyote has been used by indigenous peoples of North America for thousands of years in ritual, spiritual, and healing contextssupported
Overview of peyote alkaloids, mescaline mechanism, cultural and ceremonial context. molecules28247942
receptor-pharmacology7 · 4 ok
This ~1,000-fold to 5,000-fold potency difference at the primary target directly accounts for the mass dose disparity: 200–500 mg mescaline HCl produces effects comparable to 100 µg LSD or 20 mg psilocybin.supported
RCT comparing mescaline 300/500mg, LSD 100μg, psilocybin 20mg in 32 healthy participants. Subjective effects comparable at equipotent doses. s41386-023-01607-2
Mescaline's primary psychedelic action is mediated by agonism at 5-HT₂A receptors, with 5-HT₂C as a secondary serotonergic targetsupported
Includes Ki data for mescaline at 5-HT2A, 5-HT2C, and other receptors. journal.pone.0009019
The NIMH Psychoactive Drug Screening Program data assayed phenylalkylamine psychedelics across 49 broadly tested receptor sites; mescaline interacts with a broad receptor profile but at relatively low potency compared to indole psychedelics such as LSD and psilocin.partially supported
NIMH-PDSP receptor affinity data for 25 psychedelic drugs at 51 receptors/transporters/ion channels. Phenylalkylamines interact with 42 of 49 sites. journal.pone.0009019
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
Claim in receptor-pharmacology — inconclusiveinconclusiveworking →
McLean et al. (2006) synthesized a conformationally restricted mescaline analog, C-(4,5,6-trimethoxyindan-1-yl)methanamine, which exhibited 3-fold higher 5-HT₂A affinity and 5-fold higher potency than mescaline with equivalent efficacypartially supported
Conformationally restricted mescaline analogue with 3-fold higher 5-HT2A affinity/potency than mescaline. R-(+) isomer more potent. pmid:16821786
neuroscience6 · 4 ok
Mescaline activates 5-HT₂A receptors densely expressed on apical dendrites of layer V pyramidal neurons in the neocortexsupported
Agonists/partial agonists at 5-HT2A receptors on neocortical pyramidal cells layer V. pr.115.011478
Claim in neuroscience — inconclusiveinconclusiveworking →
However, Ley et al. (2023) found that neither mescaline, LSD, nor psilocybin acutely altered plasma BDNF levels in their comparative RCT, suggesting that circulating BDNF is not a reliable acute biomarker of psychedelic-induced neuroplasticity.supported
No BDNF changes. s41386-023-01607-2
The qualitative equivalence of mescaline, LSD, and psilocybin at equipotent doses is consistent with a shared entropic mechanism triggered by 5-HT₂A agonism.supported
Subjective effects comparable at equipotent doses. s41386-023-01607-2
Claim in neuroscience — inconclusiveinconclusiveworking →
Does mescaline's oxytocin elevation produce measurable differences in prosocial behavior, empathy, or therapeutic alliance compared to psilocybin?supported
Mescaline and LSD enhanced oxytocin; no BDNF changes. s41386-023-01607-2
chemistry3 · 0 ok
clinical-evidence3 · 3 ok
Ley et al. (2023) conducted a Phase 1, double-blind, placebo-controlled crossover trial (n=32 healthy participants) directly comparing mescaline 300 and 500 mg with LSD 100 µg and psilocybin 20 mgsupported
RCT comparing mescaline 300/500mg, LSD 100μg, psilocybin 20mg in 32 healthy participants. s41386-023-01607-2
Klaiber et al. (2024) conducted a Phase 1, double-blind, placebo-controlled, single-site RCT (n=16 healthy participants) at University Hospital Baselsupported
Randomized, double-blind, placebo-controlled crossover study in 16 healthy subjects receiving mescaline (100–800 mg) and 800 mg + ketanserin. s41398-024-03116-2
Mueller et al. (2025) published detailed pharmacokinetic-pharmacodynamic modeling and urinary recovery data for oral mescaline HCl in healthy participants.supported
Analyzed PK/PD/urinary recovery of oral mescaline HCl in healthy participants. s40262-025-01544-x
comparative-pharmacology3 · 2 ok
The Ley et al. (2023) crossover RCT provides direct head-to-head data for mescaline 500 mg, LSD 100 µg, and psilocybin 20 mg in the same participants (n=32).supported
RCT comparing mescaline 300/500mg, LSD 100μg, psilocybin 20mg in 32 healthy participants. s41386-023-01607-2
Despite this potency gap, equipotent doses produce indistinguishable subjective states on validated psychometric instruments, confirming that the pharmacodynamic endpoint — 5-HT₂A agonism — is shared across the classical psychedelic class.supported
Subjective effects comparable at equipotent doses. s41386-023-01607-2
Claim in comparative-pharmacology — inconclusiveinconclusiveworking →
pharmacokinetic-detail3 · 2 ok
Subjective effect duration scales with dose: 6.4 hours at 100 mg, increasing to approximately 14 hours at 800 mgsupported
effect duration 6.4–14h. s41398-024-03116-2
At 500 mg, mean duration is 11.1 hours — substantially longer than LSD (8.2 h) or psilocybin (4.9 h) at equipotent dosessupported
Mescaline had longest duration (mean 11.1h vs LSD 8.2h vs psilocybin 4.9h). s41386-023-01607-2
Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →
effects-overview1 · 1 ok
At equipotent doses, mescaline produces altered states qualitatively indistinguishable from LSD and psilocybin on validated psychometric scalessupported
Subjective effects comparable at equipotent doses. s41386-023-01607-2
legal-status1 · 1 ok
Mescaline is classified as a Schedule I substance under the United Nations Convention on Psychotropic Substances (1971), which prohibits manufacture, trade, and possession across signatory statespartially supported
Classical psychedelics including mescaline used extensively in psychiatry before Schedule I classification in 1967. j.neuropharm.2017.12.040