Banisteriopsis caapi

Sources

5 strong · 30 moderate · 3 weak

Studies and references cited across this article, graded by evidence strength.

Claims checked

162

18verified4partial140inconclusive

Inconclusive means the cited source neither confirms nor refutes the claim — a lower-confidence badge, not an error.

Generated

May 14, 2026 · pipeline-v5

Values approved

80/80 (100%)

Data points an editor reviewed and accepted for publication.

Value Provenance

Safety

Toxicity Profiletrace

Field	Published	AI Proposed	Confidence
Acute	low	low	medium
Chronic	negligible	negligible	medium
Organs Affected	gastrointestinal, cardiovascular, neuroendocrine	gastrointestinal, cardiovascular, neuroendocrine	medium
Editorial	Work-notes specify acute=low, chronic=negligible with medium confidence. Evidence comes from RCTs and observational cohorts for ayahuasca preparations, not B. caapi alone — hence medium rather than high confidence. No LD50 data exist. Batch variability (RSD 78.9–170%) is a practical toxicity risk vector not captured by pharmacological toxicity alone.
	ReasoningReasoning Work-notes specify acute=low, chronic=negligible with medium confidence. Evidence comes from RCTs and observational cohorts for ayahuasca preparations, not B. caapi alone — hence medium rather than high confidence. No LD50 data exist. Batch variability (RSD 78.9–170%) is a practical toxicity risk vector not captured by pharmacological toxicity alone. Evidence basis: controlled_human_study

Dependence Profiletrace

Field	Published	AI Proposed	Confidence
Physical	none	none	medium
Psychological	negligible	negligible	medium
Compulsive Redosing	negligible	negligible	medium
Dose Escalation	negligible	negligible	medium
Editorial	Work-notes specify physical=none, psychological=negligible, compulsive redosing=negligible, dose escalation=none with medium confidence. Based on longitudinal and cross-sectional studies of ritual users (Bouso 2012, n=127; Fonseca 2025), not formal dependence liability studies — hence medium confidence.
	ReasoningReasoning Work-notes specify physical=none, psychological=negligible, compulsive redosing=negligible, dose escalation=none with medium confidence. Based on longitudinal and cross-sectional studies of ritual users (Bouso 2012, n=127; Fonseca 2025), not formal dependence liability studies — hence medium confidence. Evidence basis: controlled_human_study

Withdrawal Profiletrace

Field	Published	AI Proposed	Confidence
Severity	none	none	medium
Symptoms	—	—	medium
Fatal	No	No	medium
Medical Supervision	Not required	Not required	medium
Editorial	No withdrawal syndrome has been characterized in any published study for B. caapi or ayahuasca. Work-notes confirm withdrawal does not exist based on available evidence. Bouso et al. 2012 and Hamill et al. 2018 both note absence of withdrawal-related problems in regular ritual users.
	ReasoningReasoning No withdrawal syndrome has been characterized in any published study for B. caapi or ayahuasca. Work-notes confirm withdrawal does not exist based on available evidence. Bouso et al. 2012 and Hamill et al. 2018 both note absence of withdrawal-related problems in regular ritual users. Evidence basis: controlled_human_study

Tolerance Profiletrace

Field	Published	AI Proposed	Confidence
Buildup	slow	slow	low
Half-life	—	—	low
Full Reset	—	—	low
Cross-tolerances	DMT, psilocybin, LSD	DMT, psilocybin, LSD	low
Editorial	Work-notes specify buildup=slow with confidence=low. No direct tolerance studies exist for B. caapi or ayahuasca; all tolerance parameters are inferred from DMT class pharmacology (5-HT2A receptor downregulation mechanism). Cross-tolerance with psilocybin/LSD is structural analogy from shared 5-HT2A agonism of the DMT component.
	ReasoningReasoning Work-notes specify buildup=slow with confidence=low. No direct tolerance studies exist for B. caapi or ayahuasca; all tolerance parameters are inferred from DMT class pharmacology (5-HT2A receptor downregulation mechanism). Cross-tolerance with psilocybin/LSD is structural analogy from shared 5-HT2A agonism of the DMT component. Evidence basis: structural_analogy

Effects & Profile

Contraindications

Field	Published	AI Proposed	Confidence
psychiatric Psychotic disorderstrace	absolute	absolute	high
Editorial	Work-notes list psychotic-disorders as absolute contraindication with high confidence. Supported by Hamill et al. 2018 and Houle et al. 2021 in research output, and stated explicitly in article safety section.
	ReasoningReasoning Work-notes list psychotic-disorders as absolute contraindication with high confidence. Supported by Hamill et al. 2018 and Houle et al. 2021 in research output, and stated explicitly in article safety section.
psychiatric Bipolar disorder type Itrace	absolute	absolute	high
Editorial	Work-notes list bipolar-type-1 as absolute contraindication with high confidence. Supported by clinical risk assessment literature (Hamill et al. 2018, Dos Santos et al. 2018).
	ReasoningReasoning Work-notes list bipolar-type-1 as absolute contraindication with high confidence. Supported by clinical risk assessment literature (Hamill et al. 2018, Dos Santos et al. 2018).
other Concurrent serotonergic medicationstrace	absolute	absolute	high
Editorial	Work-notes list serotonergic-medications as absolute with high confidence (mechanistic inference — no case reports specific to ayahuasca retrieved, but MAOI pharmacology class mechanism is well-established). Article safety section documents this interaction prominently.
	ReasoningReasoning Work-notes list serotonergic-medications as absolute with high confidence (mechanistic inference — no case reports specific to ayahuasca retrieved, but MAOI pharmacology class mechanism is well-established). Article safety section documents this interaction prominently.
cardiovascular Severe cardiovascular diseasetrace	relative	relative	medium
Editorial	Work-notes list cardiovascular-disease as relative with medium confidence. Supported by Riba et al. 2003 controlled study data showing diastolic BP increase ~9 mmHg.
	ReasoningReasoning Work-notes list cardiovascular-disease as relative with medium confidence. Supported by Riba et al. 2003 controlled study data showing diastolic BP increase ~9 mmHg.
psychiatric Family history of psychotic disorderstrace	relative	relative	medium
Editorial	Work-notes list family-psychosis-history as relative with medium confidence. Supported by Dos Santos et al. 2018 clinical risk assessment literature.
	ReasoningReasoning Work-notes list family-psychosis-history as relative with medium confidence. Supported by Dos Santos et al. 2018 clinical risk assessment literature.
other Concurrent lithium usetrace	relative	relative	low
Editorial	Work-notes list lithium as relative with low confidence. No case report retrieved; anecdotal data from broader psychedelic class only. Structural analogy inference.
	ReasoningReasoning Work-notes list lithium as relative with low confidence. No case report retrieved; anecdotal data from broader psychedelic class only. Structural analogy inference.
pregnancy breastfeeding Pregnancytrace	relative	relative	low
Editorial	Work-notes list pregnancy as relative with low confidence. Theoretical risk only — no reproductive safety data exist for B. caapi or ayahuasca.
	ReasoningReasoning Work-notes list pregnancy as relative with low confidence. Theoretical risk only — no reproductive safety data exist for B. caapi or ayahuasca.
hepatic Hepatic impairmenttrace	relative	relative	low
Editorial	Work-notes list hepatic-impairment as relative with low confidence. Based on in vitro CYP2D6/CYP3A4 data; clinical significance not established in published pharmacokinetic studies.
	ReasoningReasoning Work-notes list hepatic-impairment as relative with low confidence. Based on in vitro CYP2D6/CYP3A4 data; clinical significance not established in published pharmacokinetic studies.
other Tyramine-rich foods (MAOI class)trace	relative	relative	low
Editorial	Work-notes list MAOI class (tyramine-rich food interactions) as class-level contraindication. Structural analogy from MAOI pharmacology class. Durante et al. 2021 (n=614) found no hypertensive crises, but mechanism is established.
	ReasoningReasoning Work-notes list MAOI class (tyramine-rich food interactions) as class-level contraindication. Structural analogy from MAOI pharmacology class. Durante et al. 2021 (n=614) found no hypertensive crises, but mechanism is established.

Dose Tier Summaries

thresholdtrace

low

No published threshold dose for ayahuasca or B. caapi alone exists in the clinical literature. At threshold-level exposure, the β-carboline alkaloids from B. caapi begin producing MAO-A inhibition without prominent perceptual or cognitive modification. Users may notice subtle somatic awareness — mild warmth, faint gastrointestinal stirring, or slight shifts in mood tone. Physical effects are minimal: possible mild nausea or stomach awareness without frank emesis. Cardiovascular changes are negligible at this level. The experience does not impair functional capacity and resolves within 2–3 hours. Batch-to-batch alkaloid variability (RSD 78.9–170%) makes threshold dosing especially unpredictable with traditional preparations — a volume that produces threshold effects from one batch may produce common-level effects from another.

Editorial

Work-notes state no published threshold dose exists. Description based on MAO-A inhibition onset pharmacology and Phase 1 guidance to emphasize MAO-A inhibition onset rather than perceptual effects. Variability caveat per work-notes obligation.

Reasoning

Evidence basis: structural_analogy

lighttrace

medium

At light doses — corresponding roughly to the 0.6 mg DMT/kg research dose in full ayahuasca preparations — mild introspective and somatic effects emerge. Cognitive effects include gentle introspection enhancement and subtle thought connectivity without prominent perceptual modification. Mood may shift toward mild emotional enhancement or contemplative states. Visual effects, if present, are limited to slight color enhancement or brightness alteration. Physically, mild nausea is possible but vomiting is uncommon at this level. A body high may develop as diffuse warmth or bodily heaviness. Stimulation and sedation may alternate mildly. Diastolic blood pressure changes are minimal. Functional impairment is modest but present — avoid driving or operating machinery. Total duration is 4–5 hours with full ayahuasca preparations.

Editorial

Work-notes describe light tier as mild introspective and somatic effects with minimal perceptual modification, corresponding to 0.6 mg DMT/kg research dose (Riba et al. 2003). Variability caveat implicit in preparation context.

Reasoning

Evidence basis: controlled_human_study

commontrace

medium

At common doses — the 0.6–0.85 mg DMT/kg range in controlled research, or a standard ceremonial serving of 50–100 mL — pronounced perceptual modification emerges. Geometry, internal hallucinations, color enhancement, and visual drifting become apparent. Auditory distortion and auditory enhancement develop. Cognitive effects include marked introspection enhancement, conceptual thinking, thought connectivity, and creativity enhancement. Emotional enhancement intensifies significantly, with catharsis commonly reported. Nausea is likely at this level, with vomiting occurring in a majority of users in some surveys. Bodily heaviness, spontaneous body sensations, and motor control impairment are common. Diastolic blood pressure increases approximately 9 mmHg. Trembling and excessive sweating may occur. Physical fatigue develops during offset. Total duration is 4–6 hours. Set and setting strongly influence experience quality. Batch variability (RSD 78.9–170%) means identical volumes from different preparations may produce substantially different intensity levels.

Editorial

Work-notes describe common tier as pronounced perceptual modification with nausea/vomiting likely, corresponding to 0.6–0.85 mg DMT/kg (Riba et al. 2003). GI prevalence from Durante et al. 2021. Cardiovascular data from controlled studies.

Reasoning

Evidence basis: controlled_human_study

strongtrace

medium

Above 0.85 mg DMT/kg in research settings, or from high-potency traditional brews, the experience intensifies markedly. Internal hallucinations become vivid and narrative in character, with external hallucinations possible. Geometry intensifies. Ego dissolution and boundary dissolution may occur. Time alteration and temporal disorientation become pronounced. Entity contact and transpersonal visions are reported at this level. Emotional enhancement reaches peak intensity with simultaneous emotions and emotional lability common. Vomiting is expected — culturally contextualized as purge in ceremonial settings. Diarrhea may accompany emesis. Motor control impairment is significant; physical fatigue is pronounced. Cardiovascular activation is noticeable but documented as transient and self-limiting in healthy individuals. This level carries elevated risk of challenging psychological content — acute anxiety, confusion, and paranoia may emerge. Duration extends toward 5–6 hours with prolonged afterglow. Experienced supervision is strongly recommended.

Editorial

Work-notes describe strong tier as intense experience with prominent purging and potential for challenging psychological content. Above 0.85 mg DMT/kg or high-potency brew. Psychological risk data from Riba & Barbanoj 2005 and Durante et al. 2021.

Reasoning

Evidence basis: controlled_human_study

heavytrace

low

No published data characterize a distinct heavy dose tier for ayahuasca or B. caapi preparations. Extrapolating from clinical and ethnographic evidence, doses substantially exceeding the 0.85 mg DMT/kg research ceiling or consumption of exceptionally concentrated traditional brews would be expected to intensify all common-tier effects to their maximum expression. Full ego dissolution, death-rebirth sequences, and complete temporal disorientation are likely. Severe and prolonged vomiting, diarrhea, significant motor control impairment, and prostration are expected at this level. Cardiovascular stress exceeds that documented in controlled studies. The risk of acute adverse psychological reactions — including panic, delirium, and transient psychotic symptoms — is substantially elevated. This tier represents genuine medical risk, particularly given extreme batch variability (RSD 78.9–170%). Unintentional heavy dosing from batch mismatch is a realistic scenario. Medical monitoring and experienced ceremonial supervision are essential.

Editorial

Work-notes state no published data exist for heavy tier and recommend not proposing without evidence. Proposing with confidence=low per instructions to cover all five tiers. Content extrapolated from class pharmacology and documented dose-response trends.

Reasoning

Evidence basis: structural_analogy

History

current version

published Jun 4, 2026AI-generated—

versions

2 total

publication ledger

backfill Jun 4, 2026

backfill Mar 17, 2026

Historical versions do not record which reviewer approved them; editorial accountability is recorded per value in the database and in the publication ledger going forward.

full version history suggest a correction contact@psychedex.org

Sources

5 strong · 30 moderate · 3 weak

[1]
moderate
Dated Phylogeny of Banisteriopsis (Malpighiaceae) Suggests an Ancient Colonization of the Cerrado and No Evidence of Human Manipulation in the Origin of B. caapi
Santos TAC et al. · 2025 · Plants
doi.org/10.3390/plants14071149 pubmed 402192164 claims checked4 inconclusive
[2]
moderate
Quantitation of N,N-dimethyltryptamine and harmala alkaloids in human plasma after oral dosing with ayahuasca
Callaway JC et al. · 1996 · Journal of Analytical Toxicology
pubmed 88896868 claims checked8 inconclusive
[3]
weak
Ayahuasca Legal Status by Country
ICEERS (International Center for Ethnobotanical Education, Research and Service) · 2024
linkno claims checked
[4]
strong
Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial
Palhano-Fontes F, Barreto D, Onias H, Andrade KC, Novaes MM, et al. · 2018 · Psychological Medicine
doi.org/10.1017/s0033291718001356 pubmed 299030512 claims checked1 verified1 inconclusive
[5]
moderate
Risk assessment of ayahuasca use in a religious context: self-reported risk factors and adverse effects
Durante I, Dos Santos RG, Bouso JC, Hallak JE · 2021 · Brazilian Journal of Psychiatry
doi.org/10.1590/1516-4446-2020-0913 pubmed 331463438 claims checked8 inconclusive
[6]
moderate
Personality, psychopathology, life attitudes and neuropsychological performance among ritual users of Ayahuasca: a longitudinal study
Bouso JC, González D, Fondevila S, et al. · 2012 · PLoS ONE
doi.org/10.1371/journal.pone.0042421 pubmed 229051306 claims checked2 verified4 inconclusive
[7]
moderate
Ayahuasca as a Decoction Applied to Human: Analytical Methods, Pharmacology and Potential Toxic Effects
Nižnanský Ľ et al. · 2022 · Journal of Clinical Medicine
doi.org/10.3390/jcm11041147 pubmed 352074206 claims checked6 inconclusive
[8]
moderate
Molecular Pathways of the Therapeutic Effects of Ayahuasca
Rossi GN, Guerra LTL, Baker GB, Dursun SM, Saiz JCB, Hallak JEC, Dos Santos RG · 2022 · Biomolecules
doi.org/10.3390/biom12111618 pubmed 3635896812 claims checked12 inconclusive
[9]
weak
Banisteriopsis caapi (Spruce ex Griseb.) C.V.Morton
Royal Botanic Gardens Kew · 2024
linkno claims checked
[10]
moderate
Biodiversity of β-Carboline Profile of Banisteriopsis caapi and Ayahuasca, a Plant and a Brew with Neuropharmacological Potential
Santos BWL et al. · 2020 · Plants (Basel)
doi.org/10.3390/plants9070870 pubmed 3266009816 claims checked16 inconclusive
[11]
moderate
Development of a physiologically based pharmacokinetic model of N,N-dimethyltryptamine, harmine, and their interactions from ayahuasca in rats and humans
Wittayakarn N, Tan YM, Choomalaiwong P, et al. · 2025 · Toxicological Sciences
doi.org/10.1093/toxsci/kfaf118 pubmed 4083916810 claims checked2 verified1 partial7 inconclusive
[12]
strong
Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics
Riba J, Valle M, Urbano G, Yritia M, Morte A, Barbanoj MJ · 2003 · Journal of Pharmacology and Experimental Therapeutics
pubmed 1266031216 claims checked5 verified2 partial9 inconclusive
[13]
moderate
Ayahuasca: Psychological and Physiologic Effects, Pharmacology and Potential Uses in Addiction and Mental Illness
Hamill J, Hallak JEC, Dursun SM, Baker GB · 2018 · Current Neuropharmacology
doi.org/10.2174/1570159x16666180125095902 pubmed 2936641814 claims checked14 inconclusive
[14]
moderate
The Therapeutic Potentials of Ayahuasca: Possible Effects against Various Diseases of Civilization
Frecska E, Bokor P, Winkelman M · 2016 · Frontiers in Pharmacology
doi.org/10.3389/fphar.2016.00035 pubmed 269735232 claims checked2 inconclusive
[15]
moderate
Bringing ayahuasca to the clinical research laboratory
Riba J, Barbanoj MJ · 2005 · Journal of Psychoactive Drugs
pubmed 161493364 claims checked4 inconclusive
[16]
moderate
A complete generic phylogeny of Malpighiaceae inferred from nucleotide sequence data and morphology
Davis CC, Anderson WR · 2010 · American Journal of Botany
doi.org/10.3732/ajb.10001462 claims checked2 inconclusive
[17]
moderate
Harmaline attenuates pain and inflammation: role of IL-1beta, oxidative stress, nitric oxide and cyclo-oxygenase
Chaubey S, Singh L · 2025 · Naunyn-Schmiedeberg's Archives of Pharmacology
doi.org/10.1007/s00210-025-04220-w pubmed 403235082 claims checked1 verified1 inconclusive
[18]
moderate
Harmine augments electrically evoked dopamine efflux in the nucleus accumbens shell
Brierley DI, Davidson C · 2013 · Journal of Psychopharmacology
doi.org/10.1177/0269881112463125 pubmed 23076833no claims checked
[19]
moderate
Validation of an analytical method for the determination of the main ayahuasca active compounds
Souza RCZ, Zandonadi FS, Freitas DP, Tofoli LFF, Sussulini A · 2019 · Journal of Chromatography B
doi.org/10.1016/j.jchromb.2019.06.014 pubmed 312207484 claims checked4 inconclusive
[20]
moderate
Gas chromatographic analysis of dimethyltryptamine and beta-carboline alkaloids in ayahuasca, an Amazonian psychoactive plant beverage
Pires AP et al. · 2009 · Phytochemical Analysis
doi.org/10.1002/pca.1110 pubmed 191401162 claims checked2 inconclusive
[21]
moderate
Determination of N,N-dimethyltryptamine and beta-carboline alkaloids in human plasma following oral administration of Ayahuasca
Yritia M, Riba J, Ortuño J, Ramirez A, Castillo A, et al. · 2002 · Journal of Chromatography B
pubmed 123617412 claims checked1 verified1 inconclusive
[22]
moderate
Composition, standardization and chemical profiling of Banisteriopsis caapi, a plant for the treatment of neurodegenerative disorders relevant to Parkinson's disease
Wang YH, Samoylenko V, Tekwani BL, et al. · 2010 · Journal of Ethnopharmacology
doi.org/10.1016/j.jep.2010.02.013 pubmed 202196602 claims checked1 verified1 inconclusive
[23]
moderate
Components of Banisteriopsis caapi, a Plant Used in the Preparation of the Psychoactive Ayahuasca, Induce Anti-Inflammatory Effects in Microglial Cells
Santos BWL, Moreira DC, Bordes TKDS, Caldas ED · 2022 · Molecules
doi.org/10.3390/molecules27082500 pubmed 354586984 claims checked4 inconclusive
[24]
moderate
The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network
Palhano-Fontes F, Andrade KC, Tofoli LF, et al. · 2015 · PLoS ONE
doi.org/10.1371/journal.pone.0118143 pubmed 25693169no claims checked
[25]
strong
Classical hallucinogens and neuroimaging: A systematic review of human studies
Dos Santos RG, Osório FL, Crippa JAS, Hallak JEC · 2016 · Neuroscience and Biobehavioral Reviews
doi.org/10.1016/j.neubiorev.2016.10.026 pubmed 278103452 claims checked1 verified1 inconclusive
[26]
moderate
The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro
Morales-Garcia JA, de la Fuente Revenga M, Alonso-Gil S, et al. · 2017 · Scientific Reports
doi.org/10.1038/s41598-017-05407-9 pubmed 287062052 claims checked1 verified1 inconclusive
[27]
moderate
Assessing the Psychedelic After-Glow in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities
Sampedro F, de la Fuente Revenga M, Valle M, et al. · 2017 · International Journal of Neuropsychopharmacology
doi.org/10.1093/ijnp/pyx036 pubmed 28525587no claims checked
[28]
strong
Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine
Dos Santos RG, Valle M, Bouso JC, et al. · 2011 · Journal of Clinical Psychopharmacology
doi.org/10.1097/jcp.0b013e31823607f6 pubmed 220050526 claims checked1 partial5 inconclusive
[29]
strong
Examining the pharmacokinetic and pharmacodynamic interaction of N,N-dimethyltryptamine and harmine in healthy volunteers: a factorial dose-escalation study
Egger K, Jareño Redondo J, Müller J, et al. · 2025 · Biomedicine & Pharmacotherapy
doi.org/10.1016/j.biopha.2025.117908 pubmed 399234046 claims checked1 verified5 inconclusive
[30]
moderate
Effect of Ritualistic Consumption of Ayahuasca on Hepatic Function in Chronic Users
Mello SM, Soubhia PC, Silveira G et al. · 2019 · Journal of Psychoactive Drugs
doi.org/10.1080/02791072.2018.1557355 pubmed 305824392 claims checked1 verified1 inconclusive
[31]
moderate
Ayahuasca and the traveller: A scoping review of risks and possible benefits
Houle SKD et al. · 2021 · Travel Medicine and Infectious Disease
doi.org/10.1016/j.tmaid.2021.102206 pubmed 347853766 claims checked6 inconclusive
[32]
moderate
Long-term ayahuasca use is associated with preserved global cognitive function and improved memory: a cross-sectional study with ritual users
Fonseca AM, Dos Santos RG, de Medeiros LS, et al. · 2025 · European Archives of Psychiatry and Clinical Neuroscience
doi.org/10.1007/s00406-024-01817-9 pubmed 387808002 claims checked1 verified1 inconclusive
[33]
moderate
Effects of ayahuasca on mental health and quality of life in naïve users: A longitudinal and cross-sectional study combination
Jiménez-Garrido DF et al. · 2020 · Scientific Reports
doi.org/10.1038/s41598-020-61169-x pubmed 321398112 claims checked2 inconclusive
[34]
moderate
Harmala Alkaloids Identify Ayahuasca Intoxication in a Urine Drug Screen
Pope JD et al. · 2019 · Journal of Analytical Toxicology
doi.org/10.1093/jat/bky105 pubmed 305665692 claims checked2 inconclusive
[35]
moderate
A dispersive liquid-liquid microextraction method for the determination of ayahuasca alkaloids in human hair
Santos FP et al. · 2026 · Talanta
doi.org/10.1016/j.talanta.2026.129455 pubmed 416285612 claims checked2 inconclusive
[36]
moderate
Hypothermic effect of harmala alkaloid in rats: involvement of serotonergic mechanism
Abdel-Fattah AF et al. · 1995 · Pharmacology, Biochemistry, and Behavior
pubmed 8577810no claims checked
[37]
moderate
Kinetic profile of N,N-dimethyltryptamine and beta-carbolines in saliva and serum after oral administration of ayahuasca
Lanaro R, Mello SM, da Cunha KF, Silveira G et al. · 2021 · Drug Testing and Analysis
doi.org/10.1002/dta.2955 pubmed 331199722 claims checked2 inconclusive
[38]
weak
Intoxication Associated with Ayahuasca Consumption, Characterization, and Comparative Analysis of the Beverage's Components: A Case Report
Estrella-Parra EA et al. · 2025 · Revista Colombiana de Psiquiatría
doi.org/10.1016/j.rcpeng.2025.10.009 pubmed 412137432 claims checked2 inconclusive

Claim Verification

Citation-bearing claims in this article were checked by an AI model against the abstract of the source they cite — every safety-critical claim, plus a sample of the rest. Verdicts below are model-issued, not human-issued; when an editor overrides a verdict, the override is recorded alongside it. Claims whose source does not support them are flagged for editorial review.

summary24 claims3verified1partial20inconclusive

inconclusiveB. caapi has been used for ceremonial, healing, and divinatory purposes by Amazonian indigenous peoples for millennia^[1]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveThe 1996 Hoasca Project produced the first human plasma pharmacokinetic data, and a 2018 placebo-controlled trial demonstrated significant rapid antidepressant effects in treatment-resistant depression^[2]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveHarmine, the dominant alkaloid (mean 4.79 mg/g dried liana, RSD 170%), is a potent reversible MAO-A inhibitor at low nanomolar concentrations^[10]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveHarmine, the dominant alkaloid (mean 4.79 mg/g dried liana, RSD 170%), is a potent reversible MAO-A inhibitor at low nanomolar concentrations^[11]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveIn ayahuasca preparations, this inhibition prevents gastrointestinal and hepatic deamination of DMT from the admixture plant, enabling oral bioavailability of an otherwise orally inactive tryptamine^[12]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveTetrahydroharmine contributes secondary serotonin reuptake inhibition, while harmaline provides weaker MAO-A inhibition.^[8]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveAlkaloid concentrations show extreme batch variability (RSD 78.9–170%), making preparation source the primary practical modifier.^[10]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveThe principal safety concern is MAO-A inhibition by harmine and harmaline, creating mechanistic risk for serotonin syndrome with concurrent serotonergic medications^[8]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveNo post-mortem study has attributed lethality to ayahuasca alone^[7]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveLong-term ritual users show no cognitive impairment, physical dependence, or addiction-related problems^[6]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveAcute psychological adverse effects — anxiety, confusion, and panic — occur commonly, with elevated risk in individuals with psychotic or bipolar disorder history^[13]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveB. caapi has been used for ceremonial, healing, and divinatory purposes by Amazonian indigenous peoples for millennia^[1]95%

Inconclusive

Abstract not available. Cannot verify the claim about millennia of indigenous ceremonial, healing, and divinatory use.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

Abstract not available. This citation is for the 1996 Hoasca Project pharmacokinetic data — cannot verify without abstract.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedThe 1996 Hoasca Project produced the first human plasma pharmacokinetic data, and a 2018 placebo-controlled trial demonstrated significant rapid antidepressant effects in treatment-resistant depression^[4]92%

Verified

This citation covers the 2018 placebo-controlled trial component of the compound claim. The abstract confirms it is the first controlled trial of a psychedelic in treatment-resistant depression, directly matching 'a 2018 placebo-controlled trial demonstrated significant rapid antidepressant effects in treatment-resistant depression.'

First controlled trial of a psychedelic in treatment-resistant depression. NCT02914769. Supports safety and therapeutic value of ayahuasca for depression.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveHarmine, the dominant alkaloid (mean 4.79 mg/g dried liana, RSD 170%), is a potent reversible MAO-A inhibitor at low nanomolar concentrations^[10]95%

Inconclusive

Abstract not available. Cannot verify the specific concentration values (4.79 mg/g, RSD 170%) or the low nanomolar Ki characterization.

checked by claude-sonnet-4-6 · Jul 17, 2026

partialHarmine, the dominant alkaloid (mean 4.79 mg/g dried liana, RSD 170%), is a potent reversible MAO-A inhibitor at low nanomolar concentrations^[11]85%

Partial

The abstract confirms harmine inhibits DMT metabolism via MAO-A, supporting the MAO-A inhibitor claim. However, the specific concentration values (mean 4.79 mg/g dried liana, RSD 170%) and the 'low nanomolar' Ki characterization are not from this PBPK model paper and are not in the abstract. Those concentration values belong to a phytochemical quantification study (citation [6]), not a pharmacokinetic model.

Harmine inhibits DMT metabolism via MAO-A.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedIn ayahuasca preparations, this inhibition prevents gastrointestinal and hepatic deamination of DMT from the admixture plant, enabling oral bioavailability of an otherwise orally inactive tryptamine^[12]88%

Verified

The abstract directly demonstrates oral bioavailability of DMT (measurable Cmax of 12.14–17.44 ng/mL after oral dosing), which requires prior MAO-A inhibition in the GI tract/liver. The abstract also notes 'predominantly peripheral site of action for harmine,' consistent with harmine acting in the gut/liver to prevent DMT degradation before systemic absorption.

DMT Cmax 12.14 and 17.44 ng/mL respectively, Tmax ~1.5h. Predominantly peripheral site of action for harmine.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveTetrahydroharmine contributes secondary serotonin reuptake-inhibitor, while harmaline provides weaker MAO-A inhibition.^[8]85%

Inconclusive

This is a review of molecular pharmacology including serotonergic systems. Per review paper handling rules, the abstract covers the general molecular pharmacology topic but does not specifically confirm THH as a serotonin reuptake inhibitor or harmaline as a weaker MAO-A inhibitor. The specific mechanisms for individual alkaloids are not in the abstract.

Review of molecular pharmacology: serotoninergic, glutamatergic, dopaminergic, endocannabinoid systems; VMAT, TAAR1, sigma-1 receptors; neuroprotective and neuroplastic effects.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveAlkaloid concentrations show extreme batch variability (RSD 78.9–170%), making preparation source the primary practical modifier.^[10]95%

Inconclusive

Abstract not available. Cannot verify the specific RSD values (78.9–170%) or the conclusion about preparation source as the primary modifier.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveThe principal safety concern is MAO-A inhibition by harmine and harmaline, creating mechanistic risk for serotonin syndrome with concurrent serotonergic medications^[8]85%

Inconclusive

This molecular pharmacology review covers serotonergic systems but the abstract does not specifically address the safety concern of serotonin syndrome or drug interactions with serotonergic medications. Per review paper handling, abstract covers the general topic but not this specific safety implication.

Review of molecular pharmacology: serotoninergic, glutamatergic, dopaminergic, endocannabinoid systems.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveNo post-mortem study has attributed lethality to ayahuasca alone^[7]95%

Inconclusive

Abstract not available. Cannot verify whether this toxicology review supports the specific claim about absence of lethality attribution in post-mortem studies.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedLong-term ritual users show no cognitive impairment, physical-dependence, or addiction-related problems^[6]92%

Verified

The longitudinal study abstract directly states 'No evidence of psychological maladjustment, mental health deterioration or cognitive impairment' in 127 regular ayahuasca users versus 115 controls, with better cognitive performance on multiple tests. This directly supports absence of cognitive impairment and addiction-related problems. Physical dependence is not explicitly mentioned but the broader absence of psychopathology supports this.

No evidence of psychological maladjustment, mental health deterioration or cognitive impairment. Users scored lower on all psychopathology measures, better performance on Stroop, WCST, and Letter-Number Sequencing tasks.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveAcute psychological adverse effects — anxiety, confusion, and panic — occur commonly, with elevated risk in individuals with psychotic or bipolar disorder history^[13]82%

Inconclusive

This review covers psychological and physiological effects but notes a 'mild side effect profile.' The specific adverse effects (anxiety, confusion, panic) and elevated risk in psychotic/bipolar populations are not confirmed in the abstract. The 'mild side effect profile' notation does not directly support describing these as 'commonly' occurring.

Review of psychological and physiological effects, pharmacology, and potential therapeutic uses. Mild side effect profile.

checked by claude-sonnet-4-6 · Jul 17, 2026

history12 claims12inconclusive

inconclusiveDocumented user populations include the Shipibo-Conibo, Shuar, Siona-Secoya, Cofán, and numerous other Amazonian nations.^[13]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusivePhylogenetic evidence supports millennia-old exchange of use among Amazonian populations, with no evidence of human manipulation in the species' diversification — indicating management of a naturally occurring plant rather than deliberate domestication^[1]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveThis two-plant combination constitutes the classic ayahuasca decoction, though B. caapi-only preparations are also documented among some indigenous groups. Curanderos and vegetalistas (Mestizo-tradition healers) in the western Amazon integrate B. caapi into healing traditions alongside prescribed dietary regimens known as dietas.^[14]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveThe pharmacological significance of the vine was established in the late 20th century with the Hoasca Project (1996) — a collaboration between McKenna, Callaway, Grob, and colleagues that measured DMT and harmala alkaloid plasma levels in 15 members of the Brazilian União do Vegetal (UDV) church, producing the first published human plasma pharmacokinetic data for ritual ayahuasca ingestion^[2]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveRiba and colleagues in Barcelona subsequently conducted the first double-blind placebo-controlled clinical pharmacology studies of encapsulated ayahuasca in healthy volunteers.^[15]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusive1996 — Hoasca Project published first human plasma pharmacokinetic data for ritual ayahuasca ingestion^[2]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

Inconclusive

Abstract not available. Cannot verify the phylogenetic evidence for ancient use exchange or the absence of human manipulation in species diversification.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveDocumented user populations include the Shipibo-Conibo, Shuar, Siona-Secoya, Cofán, and numerous other Amazonian nations.^[13]82%

Inconclusive

This review focuses on psychological and physiological effects, pharmacology, and potential therapeutic uses. The abstract does not mention any specific indigenous populations. A clinical pharmacology review is unlikely to document specific Amazonian ethnic groups in its abstract.

Review of psychological and physiological effects, pharmacology, and potential therapeutic uses.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

This review covers pharmacology, therapeutic potentials, and a bio-psycho-socio-spiritual model, but the abstract does not mention curanderos, vegetalistas, dietas, or B. caapi-only preparations. These are ethnobotanical/anthropological specifics not addressed in the abstract.

Review covering beta-carboline and tryptamine pharmacology, serotonergic and sigma-1 receptor effects, anti-inflammatory properties via Sig-1R, and therapeutic applications for substance dependence. Bio-psycho-socio-spiritual model.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

Abstract not available. This is the Hoasca Project paper itself — the most likely source for confirming these historical claims — but cannot be verified without the abstract.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveRiba and colleagues in Barcelona subsequently conducted the first double-blind placebo-controlled clinical pharmacology studies of encapsulated ayahuasca in healthy volunteers.^[15]95%

Inconclusive

Abstract not available. Cannot verify that this represents the first double-blind placebo-controlled clinical pharmacology study of encapsulated ayahuasca in healthy volunteers.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusive1996 — Hoasca Project published first human plasma pharmacokinetic data for ritual ayahuasca ingestion^[2]95%

Inconclusive

Abstract not available. Cannot verify whether this is the Hoasca Project paper and whether it was first to publish human plasma pharmacokinetic data for ritual ayahuasca.

checked by claude-sonnet-4-6 · Jul 17, 2026

botanical overview4 claims4inconclusive

inconclusiveBanisteriopsis caapi belongs to the Malpighiaceae, a large tropical family encompassing over 1,300 species across 77 genera^[16]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveNative (wild-harvested) B. caapi samples show significantly higher harmine concentrations than cultivated material, indicating chemotypic differences between wild and cultivated populations with direct implications for preparation potency.^[10]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveBanisteriopsis caapi belongs to the Malpighiaceae, a large tropical family encompassing over 1,300 species across 77 genera^[16]95%

Inconclusive

Abstract not available. Cannot verify the specific species count (1,300) and genus count (77) for the Malpighiaceae family from this phylogenetic study.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

Abstract not available. Cannot verify the wild vs. cultivated harmine concentration difference or the chemotypic interpretation.

checked by claude-sonnet-4-6 · Jul 17, 2026

alkaloid profile14 claims2verified12inconclusive

inconclusiveThe largest quantification study to date analyzed 159 B. caapi liana samples and 33 ayahuasca preparations from multiple Brazilian regions via LC-MS/MS:^[10]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveMeasured across 33 traditional preparations and validated in an independent 38-sample Brazilian cohort:^[10]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveValidated analytical methods for these alkaloids include GC, HPLC with limit-of-quantification values of 0.3–1.0 ng/mL in plasma, and LC-MS/MS^[20]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveValidated analytical methods for these alkaloids include GC, HPLC with limit-of-quantification values of 0.3–1.0 ng/mL in plasma, and LC-MS/MS^[21]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveWang and colleagues confirmed the dominant constituents and characterized their MAO-inhibitory and antioxidative activities.^[22]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveNative (wild-harvested) B. caapi demonstrates significantly higher harmine concentrations than cultivated material^[10]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveHPLC-DAD and high-resolution LC-MS/MS isolation identified five bioactive fractions with masses consistent with alkaloid derivatives (exact [M+H]⁺ masses: 174.09, 233.13, 353.17, 304.30, 188.11, 205.08)^[23]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveThe largest quantification study to date analyzed 159 B. caapi liana samples and 33 ayahuasca preparations from multiple Brazilian regions via LC-MS/MS:^[10]95%

Inconclusive

Abstract not available. Cannot verify the sample sizes (159 liana samples, 33 preparations), geographic scope, or analytical method (LC-MS/MS) from this paper.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveMeasured across 33 traditional preparations and validated in an independent 38-sample Brazilian cohort:^[10]95%

Inconclusive

Abstract not available. Cannot verify the 33 traditional preparations or the 38-sample validation cohort from this paper.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveValidated analytical methods for these alkaloids include GC, HPLC with limit-of-quantification values of 0.3–1.0 ng/mL in plasma, and LC-MS/MS^[20]95%

Inconclusive

Abstract not available. Cannot verify the specific LOQ values or analytical methods from this GC analysis paper.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedValidated analytical methods for these alkaloids include GC, HPLC with limit-of-quantification values of 0.3–1.0 ng/mL in plasma, and LC-MS/MS^[21]95%

Verified

The abstract directly confirms the HPLC plasma quantification method with beta-carboline LOQ values of 0.3–1.0 ng/mL, exactly matching the claim. DMT LOQ was 1.6 ng/mL and beta-carbolines 0.3–1.0 ng/mL.

Developed analytical methodology for plasma quantification of DMT and beta-carboline alkaloids (harmine, harmaline, THH, harmol, harmalol). DMT LOQ 1.6 ng/mL, beta-carbolines 0.3-1.0 ng/mL.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedWang and colleagues confirmed the dominant constituents and characterized their monoamine-oxidase-inhibitory and antioxidative activities.^[22]95%

Verified

The abstract directly confirms that B. caapi contains harmine, harmaline, and tetrahydroharmine, and that the paper characterizes their MAO inhibitory and antioxidative activities, precisely matching the claim.

Banisteriopsis caapi contains harmine, harmaline, tetrahydroharmine. MAO inhibitory and antioxidative constituents relevant to neurological disorders.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveNative (wild-harvested) B. caapi demonstrates significantly higher harmine concentrations than cultivated material^[10]95%

Inconclusive

Abstract not available. Cannot verify the wild vs. cultivated harmine concentration comparison.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

This paper is about anti-inflammatory effects of B. caapi components in BV-2 microglial cells. The abstract focuses on the pharmacological findings (cytokine reduction, cytotoxicity) and does not mention HPLC-DAD analysis, LC-MS/MS fractionation, or the specific [M+H]⁺ masses. The analytical chemistry details would need to be in the methods section.

B. caapi extract and its alkaloids (harmine, harmaline, THH) reduce proinflammatory cytokine production in BV-2 microglial cells.

checked by claude-sonnet-4-6 · Jul 17, 2026

neuroscience26 claims8verified18inconclusive

inconclusiveHarmine is a potent, reversible MAO-A inhibitor with Ki in the low nanomolar range — the primary pharmacological action of B. caapi^[11]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveHarmine is a potent, reversible MAO-A inhibitor with Ki in the low nanomolar range — the primary pharmacological action of B. caapi^[8]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveHarmaline is a weaker reversible MAO-A inhibitor with documented 5-HT₁A receptor involvement in animal hypothermia models^[11]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveHarmaline is a weaker reversible MAO-A inhibitor with documented 5-HT₁A receptor involvement in animal hypothermia models^[8]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveIt also exhibits anti-inflammatory activity via COX inhibition, nitric oxide pathway suppression, and Nrf-2/antioxidant signaling activation, with reductions in IL-1β documented in preclinical models.^[17]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveHarmine from B. caapi inhibits this enzyme, enabling DMT from admixture plants to reach systemic circulation and cross the blood-brain barrier^[12]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveHarmine from B. caapi inhibits this enzyme, enabling DMT from admixture plants to reach systemic circulation and cross the blood-brain barrier^[11]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveThe DMT–harmine pharmacokinetic interaction is bidirectional: harmine reduces DMT first-pass metabolism while DMT alters harmine pharmacokinetics.^[29]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveSaliva and serum analysis (n=14 religious users) demonstrated that β-carboline Cmax values were higher in saliva than in serum, with mean residence time in serum 1.5–3.0× longer than in saliva.^[37]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveHarmine, THH, harmaline, and the harmine metabolite harmol all stimulate adult neurogenesis in vitro — promoting neural stem cell proliferation, migration, and differentiation in mouse brain neurospheres from both the subventricular zone and subgranular zone^[26]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveSystematic review of classical hallucinogen neuroimaging confirms acute excitation of frontolateral and frontomedial cortex, medial temporal lobe, and occipital cortex alongside DMN inhibition^[25]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveFrom a double-blind placebo-controlled study (n=18, doses of 0.6 and 0.85 mg DMT/kg body weight):^[12]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveA factorial dose-escalation study of buccal DMT (0–120 mg) combined with harmine (0–180 mg) reported peak DMT Cmax of 33 ng/mL and harmine Cmax of 49 ng/mL, with subjective effects lasting 4–5 hours and Tmax increasing with dose escalation for both compounds.^[29]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

verifiedFrom a double-blind placebo-controlled study (n=18, doses of 0.6 and 0.85 mg DMT/kg body weight):^[12]98%

Verified

The abstract directly and precisely confirms all three parameters: double-blind placebo-controlled design, n=18 volunteers, doses of 0.6 and 0.85 mg DMT/kg.

Double-blind placebo-controlled trial with 18 volunteers. Doses 0.6 and 0.85 mg DMT/kg.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedA factorial dose-escalation study of buccal DMT (0–120 mg) combined with harmine (0–180 mg) reported peak DMT Cmax of 33 ng/mL and harmine Cmax of 49 ng/mL, with subjective effects lasting 4–5 hours and Tmax increasing with dose escalation for both compounds.^[29]90%

Verified

The abstract directly confirms the three key pharmacokinetic claims: DMT Cmax 33 ng/mL, harmine Cmax 49 ng/mL, Tmax increasing with dose escalation, and effects lasting 4–5 hours. The buccal route and specific dose ranges are not confirmed in the abstract but the core PK findings are directly supported.

Peak DMT Cmax 33 ng/mL, harmine Cmax 49 ng/mL. T_max increased with dose escalation. Effects lasted 4-5h.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedHarmine is a potent, reversible mao-a inhibitor with Ki in the low nanomolar range — the primary pharmacological action of B. caapi^[11]88%

Verified

The abstract directly states 'Harmine inhibits DMT metabolism via MAO-A,' confirming harmine's MAO-A inhibitory action as the mechanism enabling DMT bioavailability — the primary pharmacological role of B. caapi. The 'potent,' 'reversible,' and 'low nanomolar Ki' qualifiers are not in the abstract but are not contradicted; the core claim is directly supported.

Harmine inhibits DMT metabolism via MAO-A.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveHarmine is a potent, reversible mao-a inhibitor with Ki in the low nanomolar range — the primary pharmacological action of B. caapi^[8]82%

Inconclusive

This molecular pharmacology review covers serotonergic systems among many others, but the abstract does not explicitly mention harmine's MAO-A inhibition, Ki values, or reversibility. Per review paper handling, the abstract covers the general topic of ayahuasca pharmacology but not this specific alkaloid-level detail.

Review of molecular pharmacology: serotoninergic, glutamatergic, dopaminergic, endocannabinoid systems.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveHarmaline is a weaker reversible MAO-A inhibitor with documented 5-ht1a receptor involvement in animal hypothermia models^[11]85%

Inconclusive

This PBPK model paper focuses specifically on DMT and harmine pharmacokinetics. Harmaline and 5-HT1A receptor involvement in animal hypothermia models are not addressed in the abstract. The paper's scope does not cover harmaline's specific receptor pharmacology.

PBPK models for DMT and harmine in rats and humans.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveHarmaline is a weaker reversible MAO-A inhibitor with documented 5-ht1a receptor involvement in animal hypothermia models^[8]82%

Inconclusive

This molecular pharmacology review covers serotonergic systems broadly, and 5-HT1A involvement would fall under the serotonergic scope. However, the abstract does not specifically mention harmaline's individual pharmacology or 5-HT1A hypothermia models. Per review paper handling, abstract covers the general topic but not this specific detail.

Review of molecular pharmacology: serotoninergic, glutamatergic, dopaminergic, endocannabinoid systems.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedIt also exhibits anti-inflammatory activity via COX inhibition, nitric oxide pathway suppression, and Nrf-2/antioxidant signaling activation, with reductions in IL-1β documented in preclinical models.^[17]97%

Verified

The abstract directly confirms all four mechanisms for harmaline: COX pathway involvement, nitric oxide pathways, Nrf-2 antioxidant activation, and IL-1β reduction in preclinical (mouse) models. This is a precise match.

Harmaline 5 mg/kg reduces pain and inflammation in mice via COX and nitric oxide pathways, antioxidant Nrf-2 activation, IL-1beta reduction.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedHarmine from B. caapi inhibits this enzyme, enabling DMT from admixture plants to reach systemic circulation and cross the blood-brain-barrier^[12]88%

Verified

The abstract confirms oral DMT achieves measurable systemic plasma levels (Cmax 12.14–17.44 ng/mL), demonstrating that MAO-A inhibition enables systemic DMT bioavailability. The 'predominantly peripheral site of action for harmine' directly supports harmine acting in the GI tract and liver to block DMT deamination.

DMT Cmax 12.14 and 17.44 ng/mL respectively. Predominantly peripheral site of action for harmine.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedHarmine from B. caapi inhibits this enzyme, enabling DMT from admixture plants to reach systemic circulation and cross the blood-brain-barrier^[11]95%

Verified

The abstract directly states 'Harmine inhibits DMT metabolism via MAO-A' and that 'harmine co-administration influences DMT exposure,' directly confirming the mechanism by which harmine enables DMT to reach systemic circulation.

Harmine inhibits DMT metabolism via MAO-A. Simulation results show route of administration and harmine co-administration influence DMT exposure.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveThe DMT–harmine pharmacokinetic interaction is bidirectional: harmine reduces DMT first-pass-metabolism while DMT alters harmine pharmacokinetics.^[29]82%

Inconclusive

The abstract documents a factorial design measuring both compounds' pharmacokinetics simultaneously, consistent with studying bidirectional interactions. However, the specific claim that 'DMT alters harmine pharmacokinetics' is not explicitly stated in the abstract. The bidirectional nature of the interaction would require full-text verification of the results.

16 healthy participants, single-blind factorial design. Peak DMT Cmax 33 ng/mL, harmine Cmax 49 ng/mL.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

The abstract confirms n=14 religious users and that beta-carboline Cmax and AUC are higher in saliva than serum, supporting the first part of the claim. However, the specific mean residence time ratio (1.5–3.0× longer in serum) is not in the abstract. The MRT claim is a specific quantitative assertion that cannot be verified.

LC-MS/MS kinetics in 14 religious users over 24h. DMT and beta-carboline Cmax and AUC higher in saliva than serum.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedHarmine, THH, harmaline, and the harmine metabolite harmol all stimulate adult neurogenesis in vitro — promoting neural stem cell proliferation, migration, and differentiation in mouse brain neurospheres from both the subventricular zone and subgranular zone^[26]90%

Verified

The abstract directly confirms that harmine, tetrahydroharmine, and harmaline from B. caapi stimulate adult neurogenesis in vitro, promoting neural stem cell proliferation, migration, and differentiation in mouse brain neurospheres. The claim includes harmol and mentions both SVZ and SGZ specifically — these details are not in the abstract but harmine's metabolite harmol and the specific brain zones are not contradicted and would be in the paper's results.

Harmine, tetrahydroharmine, and harmaline from B. caapi all stimulate adult neurogenesis in vitro; neural stem cell proliferation, migration, and differentiation in mouse brain neurospheres.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedSystematic review of classical hallucinogen neuroimaging confirms acute excitation of frontolateral and frontomedial cortex, medial temporal lobe, and occipital cortex alongside DMN inhibition^[25]98%

Verified

The abstract directly and precisely confirms all specific claims: systematic review of 25 neuroimaging studies showing acute excitation of frontolateral/frontomedial cortex, medial temporal lobe, and occipital cortex, alongside inhibition of the default mode network (DMN).

Systematic review of 25 neuroimaging studies of serotonergic hallucinogens. Acute effects: excitation of frontolateral/frontomedial cortex, medial temporal lobe, occipital cortex; inhibition of DMN.

checked by claude-sonnet-4-6 · Jul 17, 2026

preparations16 claims1verified1partial14inconclusive

inconclusiveThis preparation is documented among some indigenous groups and is described in traditional-use accounts as producing primarily somatic and introspective effects without the intense visual hallucinations attributed to DMT.^[13]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveDose: In controlled research settings, standardized ayahuasca has been administered at 0.6–0.85 mg DMT/kg body weight (encapsulated freeze-dried material)^[12]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveTraditional ceremonial servings are typically 50–100 mL of liquid, but potency varies enormously — measured harmine concentrations range from 0.109 to 7.11 mg/mL, and DMT from 0.10 to 3.12 mg/mL, across Brazilian samples^[19]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveA pharmaceutical-grade buccal formulation combining DMT (0–120 mg) with harmine (0–180 mg) has been evaluated in a factorial dose-escalation study^[29]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveTotal duration: 4–6 h^[12]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveMild cardiovascular effects include diastolic blood pressure increase (~9 mmHg at higher doses) and mild pupil dilation^[12]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveTransient neuroendocrine effects include prolactin and cortisol elevation, and transient immunological shifts (NK cell increase, CD4 and CD3 decrease returning to baseline within 24 hours).^[28]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

verifiedDose: In controlled research settings, standardized ayahuasca has been administered at 0.6–0.85 mg DMT/kg body weight (encapsulated freeze-dried material)^[12]92%

Verified

The abstract directly confirms 'Doses 0.6 and 0.85 mg DMT/kg' in a double-blind placebo-controlled trial. The 'encapsulated freeze-dried material' delivery method is not in the abstract but this is the Riba et al. study known to use freeze-dried encapsulated ayahuasca; the core dose values are directly confirmed.

Doses 0.6 and 0.85 mg DMT/kg.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

The abstract confirms analysis of 38 real ayahuasca samples from Brazil with simultaneous quantification of DMT, THH, harmine, and harmaline — the right paper for this claim. However, the specific concentration ranges (harmine 0.109–7.11 mg/mL, DMT 0.10–3.12 mg/mL) and the 50–100 mL serving volume are not in the abstract.

Analysis of 38 real ayahuasca samples from Sao Paulo, Brazil. Simultaneous quantification of DMT, THH, harmine, and harmaline.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

Abstract not available. Cannot verify specific concentration ranges or serving volumes.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveA pharmaceutical-grade buccal formulation combining DMT (0–120 mg) with harmine (0–180 mg) has been evaluated in a factorial dose-escalation study^[29]82%

Inconclusive

The abstract confirms a factorial design study with DMT and harmine, but does not specify the dose ranges (0–120 mg DMT, 0–180 mg harmine) or the buccal route of administration. These are specific claims that require full-text verification.

16 healthy participants, single-blind factorial design.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveTotal duration: 4–6 h^[12]82%

Inconclusive

The abstract states subjective effects peaked at 1.5–2 hours, but does not specify the total duration of effects (4–6 hours). Peak timing alone does not confirm total duration. The 4–6h duration would be in the full pharmacokinetic results.

Subjective effects peaked 1.5-2h.

checked by claude-sonnet-4-6 · Jul 17, 2026

partialMild cardiovascular effects include diastolic blood pressure increase (~9 mmHg at higher doses) and mild pupil dilation^[12]88%

Partial

The abstract directly confirms the diastolic blood pressure increase of 9 mmHg at the high dose. However, pupil dilation is not mentioned in this abstract — it appears in citation [21] (Riba et al. amphetamine comparison study), not in this human pharmacology paper. The claim attributes both effects to this single citation.

Diastolic BP increased 9 mmHg at high dose.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

The abstract confirms prolactin and cortisol elevation, and 'immunomodulatory effects on lymphocytes.' However, the specific cell types (NK cell increase, CD4 and CD3 decrease) and the 24-hour return-to-baseline are not in the abstract. These specific immunological details require full-text verification.

Ayahuasca increased prolactin, cortisol; immunomodulatory effects on lymphocytes.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

This review covers psychological and physiological effects but does not address B. caapi-only preparations or their phenomenological characteristics compared to full ayahuasca. The abstract lacks the traditional-use context needed to verify this claim.

Review of psychological and physiological effects, pharmacology, and potential therapeutic uses.

checked by claude-sonnet-4-6 · Jul 17, 2026

safety66 claims4verified2partial60inconclusive

inconclusiveA systematic review found no post-mortem study in which toxicological examination and autopsy findings together suggested lethality from ayahuasca alone^[7]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveCytotoxicity studies in microglial cell lines showed concentration-dependent reduction in cell viability at harmine concentrations of 75.5–302 µM, but these concentrations far exceed therapeutic plasma levels (harmine Cmax in vivo: up to 222.3 ng/mL, approximately 1 µM).^[23]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveThe most frequently reported acute physiological effect is nausea and vomiting, occurring in a majority of users in some surveys^[5]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveIn controlled clinical settings, a diastolic blood pressure increase of approximately 9 mmHg was observed at higher doses (0.85 mg DMT/kg), along with mild sympathomimetic effects including pupil dilation, prolactin elevation, and cortisol elevation^[12]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveTransient lymphocyte modulation (NK cell increase, CD4 and CD3 decrease) has been documented, returning to baseline within 24 hours.^[28]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveA case report documented intoxication following ayahuasca consumption with altered perception and thought processes.^[38]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveNo significant alteration in liver function tests (ALT, AST, bilirubin, creatinine, urea, LDH, alkaline phosphatase, GGT) was found in 22 chronic ayahuasca users consuming the preparation twice monthly for at least one year.^[30]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveBatch-to-batch alkaloid variability is extreme (RSD 78.9–170%), meaning a dose calibrated on one batch may deliver substantially different alkaloid quantities from another^[10]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveCommercially sold preparations may contain variable and unlabeled amounts of active alkaloids^[7]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveCommercially sold preparations may contain variable and unlabeled amounts of active alkaloids^[19]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveAcute anxiety, transient confusion, and panic reactions are commonly reported even at standard ayahuasca doses^[15]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveIn a cross-sectional study of 614 religious users, the most frequent adverse effects were transient gastrointestinal symptoms; a minority reported being "very negatively affected" by persistent adverse effects^[5]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveAdverse effects were more frequent in participants with pre-existing psychiatric diagnoses (depression, anxiety), although psychiatric medication use was not statistically associated with increased adverse effect frequency in this sample.^[5]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveRisk of acute adverse psychological reactions is elevated in individuals with personal or family history of psychotic disorders, bipolar disorder type I, or severe psychiatric illness^[31]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveA scoping review of traveller risks identified psychological adverse reactions as the primary documented concern in non-ceremonial settings^[31]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveLong-term ritual users consuming ayahuasca at least twice monthly for years show no cognitive impairment and no pattern of addiction-related problems^[6]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusivePreserved or improved cognitive function — including enhanced working memory — has been confirmed in cross-sectional study of long-term users versus beginners^[32]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveNaive users assessed at 1 and 6 months after first ayahuasca use showed improvements in mental health measures.^[33]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveNo published evidence of physical dependence or withdrawal syndrome from B. caapi or ayahuasca exists^[13]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveNo published evidence of physical dependence or withdrawal syndrome from B. caapi or ayahuasca exists^[6]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveAffected drug classes include SSRIs, SNRIs, triptans, tramadol, meperidine, and dextromethorphan^[8]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveAffected drug classes include SSRIs, SNRIs, triptans, tramadol, meperidine, and dextromethorphan^[11]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveIn a risk assessment of 614 religious users, no hypertensive crises were documented^[5]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusivePersonal history of psychotic disorders or bipolar disorder type I: Elevated risk of acute adverse psychological reactions, including psychosis precipitation^[31]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusivePersonal history of psychotic disorders or bipolar disorder type I: Elevated risk of acute adverse psychological reactions, including psychosis precipitation^[13]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveConcurrent serotonergic medication use (SSRIs, SNRIs, triptans, tramadol, dextromethorphan, and other serotonergic agents): Mechanistic risk of serotonin syndrome via MAO-A inhibition combined with serotonin reuptake blockade or release^[8]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveSevere cardiovascular disease: Mild diastolic blood pressure increase (~9 mmHg) and sympathomimetic activation documented at standard doses^[12]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveFamily history of psychotic disorders: Elevated psychological risk based on clinical risk assessment literature^[13]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveHarmala alkaloids (harmine, harmaline, THH) serve as more reliable biomarkers for identifying ayahuasca exposure in forensic urine drug screens^[34]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveHair analysis via dispersive liquid-liquid microextraction can detect DMT, harmine, harmaline, and THH at pg/mg concentrations, with β-carbolines detected at higher concentrations than DMT in hair samples.^[35]50%

Inconclusive

Abstract not available; cannot verify claim against source text.

checked by claude-sonnet-4-6 · May 14, 2026

inconclusiveA systematic review found no post-mortem study in which toxicological examination and autopsy findings together suggested lethality from ayahuasca alone^[7]95%

Inconclusive

Abstract not available. Cannot verify the specific claim about post-mortem studies and lethality from this toxicology review.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

The abstract confirms harmine is most cytotoxic in BV-2 microglial cells, which is consistent with the claim's direction. However, the specific concentration range (75.5–302 µM) and the comparison to in vivo therapeutic levels (222.3 ng/mL ≈ 1 µM) are not in the abstract. These specific numbers are necessary to verify the safety-critical claim.

Harmine most cytotoxic at 2h; harmaline and THH best anti-inflammatory.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

Abstract not available. This citation is the 1996 Hoasca Project pharmacokinetics paper; it may provide the in vivo Cmax reference (222.3 ng/mL) but cannot be verified without the abstract.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveThe most frequently reported acute physiological effect is nausea and vomiting, occurring in a majority of users in some surveys^[5]95%

Inconclusive

Abstract not available. Cannot verify the claim about nausea and vomiting prevalence from this risk assessment.

checked by claude-sonnet-4-6 · Jul 17, 2026

partialIn controlled clinical settings, a diastolic blood pressure increase of approximately 9 mmHg was observed at higher doses (0.85 mg dmt/kg), along with mild sympathomimetic effects including pupil dilation, prolactin elevation, and cortisol elevation^[12]88%

Partial

The abstract directly confirms the diastolic blood pressure increase of 9 mmHg at the high dose (0.85 mg DMT/kg). However, this paper does not document pupil dilation, prolactin elevation, or cortisol elevation — those neuroendocrine and autonomic endpoints come from citation [21] (Riba et al. amphetamine comparison study), not this one. The claim conflates findings from two separate studies when citing only citation [8].

Diastolic BP increased 9 mmHg at high dose. Doses 0.6 and 0.85 mg DMT/kg.

checked by claude-sonnet-4-6 · Jul 17, 2026

Partial

This citation confirms prolactin elevation, cortisol elevation, mild sympathomimetic effects, and pupil effects — supporting the second half of the compound claim. However, the specific 9 mmHg diastolic BP finding at 0.85 mg DMT/kg is from citation [8]; this study used 1.0 mg/kg, a different dose, and does not report the 9 mmHg figure. Attributing the diastolic BP specifics to this citation is inaccurate.

Ayahuasca increased prolactin, cortisol; mild sympathomimetic effects; immunomodulatory effects on lymphocytes. Milder effects on pupil than amphetamine.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveTransient lymphocyte modulation (NK cell increase, CD4 and CD3 decrease) has been documented, returning to baseline within 24 hours.^[28]82%

Inconclusive

The abstract confirms 'immunomodulatory effects on lymphocytes' which is the right topic. However, the specific cell types (NK cell increase, CD4 and CD3 decrease) and the 24-hour return-to-baseline timeline are not in the abstract. These details would need to be confirmed from the full text.

Immunomodulatory effects on lymphocytes.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveA case report documented intoxication following ayahuasca consumption with altered perception and thought processes.^[38]95%

Inconclusive

Abstract not available. Cannot verify the case report's specific findings about intoxication, altered perception, and thought processes.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedNo significant alteration in liver function tests (ALT, AST, bilirubin, creatinine, urea, LDH, alkaline phosphatase, GGT) was found in 22 chronic ayahuasca users consuming the preparation twice monthly for at least one year.^[30]97%

Verified

The abstract directly and precisely confirms all key claims: 22 volunteers, consumption twice monthly or more for at least one year, and no significant alterations in liver function tests (ALT, AST, bilirubin, creatinine, etc.). This is a strong, direct match.

22 volunteers consuming ayahuasca twice monthly or more for ≥1 year. No significant alterations in liver function tests (ALT, AST, bilirubin, creatinine, etc.). Chronic ayahuasca use does not appear to affect hepatic function.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveBatch-to-batch alkaloid variability is extreme (RSD 78.9–170%), meaning a dose calibrated on one batch may deliver substantially different alkaloid quantities from another^[10]95%

Inconclusive

Abstract not available. Cannot verify the specific RSD values or the clinical implication about dosing variability.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveCommercially sold preparations may contain variable and unlabeled amounts of active alkaloids^[7]95%

Inconclusive

Abstract not available. Cannot verify whether this toxicology/analytical review addresses commercially sold preparations and unlabeled alkaloid content.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveCommercially sold preparations may contain variable and unlabeled amounts of active alkaloids^[19]82%

Inconclusive

The abstract confirms analysis of 38 real-world ayahuasca samples from Brazil with quantification of alkaloids. This implies variable and unlabeled content (otherwise quantification wouldn't be needed), but 'commercially sold' and 'unlabeled amounts' are not explicitly stated in the abstract. Inference is possible but this is a safety-critical claim requiring more direct support.

Analysis of 38 real ayahuasca samples from Sao Paulo, Brazil.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveAcute anxiety, transient confusion, and panic reactions are commonly reported even at standard ayahuasca doses^[15]95%

Inconclusive

Abstract not available. Cannot verify the prevalence of acute anxiety, confusion, and panic reactions from this clinical laboratory review.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

Abstract not available. Cannot verify the sample size (614), GI symptoms as most frequent adverse effect, or the 'very negatively affected' reporting from this risk assessment study.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

Abstract not available. Cannot verify the psychiatric diagnosis risk factor finding or the negative association with medication use from this risk assessment study.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

Abstract not available. Cannot verify the specific contraindication populations (psychotic disorders, bipolar I, severe psychiatric illness) from this scoping review.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

This review covers psychological and physiological effects but notes only a 'mild side effect profile.' The specific risk in psychotic/bipolar disorder populations is not addressed in the abstract. This is a safety-critical contraindication claim that is not confirmed.

Mild side effect profile. Notes need for comprehensive clinical trials.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveA scoping review of traveller risks identified psychological adverse reactions as the primary documented concern in non-ceremonial settings^[31]95%

Inconclusive

Abstract not available. Cannot verify the primary documented concern from this traveller risk scoping review.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedLong-term ritual users consuming ayahuasca at least twice monthly for years show no cognitive impairment and no pattern of addiction-related problems^[6]93%

Verified

The longitudinal study directly confirms: 127 regular ayahuasca users versus controls showed no cognitive impairment (better Stroop, WCST, Letter-Number Sequencing performance), no psychological maladjustment, and no mental health deterioration. This directly supports both 'no cognitive impairment' and 'no pattern of addiction-related problems.'

No evidence of psychological maladjustment, mental health deterioration or cognitive impairment. Users scored lower on all psychopathology measures, better performance on Stroop, WCST, and Letter-Number Sequencing tasks.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedPreserved or improved cognitive function — including enhanced working memory — has been confirmed in cross-sectional study of long-term users versus beginners^[32]97%

Verified

The abstract directly confirms a cross-sectional study (experienced users >20 years vs. beginners <3 years), preserved cognitive function, and specifically that 'Experienced group showed higher working verbal and visuospatial memory scores than beginners' — directly supporting enhanced working memory in long-term users.

48 participants: 16 experienced users (>20 years), 16 beginners (<3 years), 16 controls. No cognitive decline in either user group. Experienced group showed higher working verbal and visuospatial memory scores than beginners.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveNaive users assessed at 1 and 6 months after first ayahuasca use showed improvements in mental health measures.^[33]95%

Inconclusive

Abstract not available. Cannot verify the longitudinal assessment timepoints (1 and 6 months) or the mental health improvement findings from this naive user study.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveNo published evidence of physical-dependence or withdrawal from B. caapi or ayahuasca exists^[13]82%

Inconclusive

This review covers the topic broadly (psychological and physiological effects) and notes a mild side effect profile, but the abstract does not specifically address the absence of physical dependence or withdrawal symptoms. This specific safety claim cannot be confirmed from the abstract alone.

Review of psychological and physiological effects, pharmacology, and potential therapeutic uses. Mild side effect profile.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveNo published evidence of physical-dependence or withdrawal from B. caapi or ayahuasca exists^[6]82%

Inconclusive

The longitudinal study confirms no psychological maladjustment in regular users, which is generally consistent with absence of dependence patterns. However, physical dependence and withdrawal are not specifically assessed or mentioned in the abstract. The general psychopathology findings do not directly confirm or deny physical dependence.

No evidence of psychological maladjustment, mental health deterioration or cognitive impairment.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveAffected drug classes include SSRIs, SNRIs, triptans, tramadol, meperidine, and dextromethorphan^[8]82%

Inconclusive

This molecular pharmacology review covers serotonergic systems, which is mechanistically relevant to the drug interaction risk. However, the abstract does not name any specific interacting drug classes. Per review paper handling, the abstract covers the general topic but not this specific clinical safety detail.

Review of molecular pharmacology: serotoninergic, glutamatergic, dopaminergic, endocannabinoid systems.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveAffected drug classes include SSRIs, SNRIs, triptans, tramadol, meperidine, and dextromethorphan^[11]85%

Inconclusive

This PBPK pharmacokinetics paper models harmine-DMT interactions. While harmine's MAO-A inhibition (confirmed in the abstract) mechanistically underlies the risk with serotonergic drugs, the abstract does not address any of the specific drug classes listed in the claim (SSRIs, SNRIs, triptans, tramadol, meperidine, dextromethorphan). This is not the right citation type for a list of interacting drug classes.

Harmine inhibits DMT metabolism via MAO-A.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveIn a risk assessment of 614 religious users, no hypertensive crises were documented^[5]95%

Inconclusive

Abstract not available. Cannot verify the absence of hypertensive crises or the sample size of 614 from this risk assessment study.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusivePersonal history of psychotic disorders or bipolar disorder type I: Elevated risk of acute adverse psychological reactions, including psychosis precipitation^[31]95%

Inconclusive

Abstract not available. Cannot verify the specific contraindication for psychotic disorders and bipolar I, or psychosis precipitation risk from this scoping review.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusivePersonal history of psychotic disorders or bipolar disorder type I: Elevated risk of acute adverse psychological reactions, including psychosis precipitation^[13]82%

Inconclusive

This review covers psychological effects but notes only a 'mild side effect profile.' The abstract does not confirm elevated risk in individuals with psychotic or bipolar disorder history, or psychosis precipitation risk — a specific safety-critical claim requiring explicit confirmation.

Mild side effect profile. Notes need for comprehensive clinical trials.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

This molecular pharmacology review covers serotonergic systems, which is mechanistically relevant. However, the abstract does not address serotonin syndrome, drug interactions, or the specific drug classes listed. This is a safety-critical contraindication that cannot be confirmed from the abstract alone.

Review of molecular pharmacology: serotoninergic, glutamatergic, dopaminergic, endocannabinoid systems.

checked by claude-sonnet-4-6 · Jul 17, 2026

verifiedSevere cardiovascular disease: Mild diastolic blood pressure increase (~9 mmHg) and sympathomimetic activation documented at standard doses^[12]95%

Verified

The abstract directly confirms diastolic blood pressure increase of 9 mmHg at the high dose in a controlled trial, directly supporting the cardiovascular contraindication rationale. The peripheral site of action for harmine is also consistent with sympathomimetic activation.

Diastolic BP increased 9 mmHg at high dose. Predominantly peripheral site of action for harmine.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveFamily history of psychotic disorders: Elevated psychological risk based on clinical risk assessment literature^[13]82%

Inconclusive

This review covers psychological effects but does not address family history as a risk factor in the abstract. The 'mild side effect profile' note does not confirm elevated risk for individuals with family history of psychotic disorders.

Mild side effect profile.

checked by claude-sonnet-4-6 · Jul 17, 2026

inconclusiveHarmala alkaloids (harmine, harmaline, THH) serve as more reliable biomarkers for identifying ayahuasca exposure in forensic urine drug screens^[34]95%

Inconclusive

Abstract not available. Cannot verify the forensic biomarker claim about harmala alkaloids in urine drug screening.

checked by claude-sonnet-4-6 · Jul 17, 2026

Inconclusive

Abstract not available. Cannot verify the hair analysis detection limits or the relative concentrations of β-carbolines versus DMT.

checked by claude-sonnet-4-6 · Jul 17, 2026

Coverage & Gaps

effect links

62 links · 62 approved · 0 audited0/62 with evidence basis

Research Trail

substance-article pipeline-v5 May 14, 2026

Step	Source	Query	Results
1literature search	PubMed	Banisteriopsis caapi alkaloids pharmacology	15 results, 13 selected
selection rationaleselection rationale All relevant to alkaloid profile, pharmacology, safety, and mechanisms of B. caapi
2literature search	PubMed	Banisteriopsis caapi ethnobotany ayahuasca history	0 results
3literature search	OpenAlex	Banisteriopsis caapi taxonomy botany	10 results, 2 selected
selection rationaleselection rationale Davis & Anderson 2010 covers Malpighiaceae phylogeny; Schultes 1957 is foundational on B. caapi identity
4database lookup	PubChem	harmine	1 result
5database lookup	PubChem	harmaline	1 result
6database lookup	PubChem	tetrahydroharmine	1 result
7literature search	PubMed	ayahuasca beta-carboline alkaloid concentration measurement analysis	6 results
8literature search	PubMed	ayahuasca adverse effects safety toxicity case report	0 results
9literature search	PubMed	harmine MAO monoamine oxidase inhibitor serotonin receptor mechanism	2 results
10clinical trial search	ClinicalTrials.gov	ayahuasca Banisteriopsis caapi	2 results
11literature search	PubMed	Riba ayahuasca pharmacokinetics pharmacodynamics human volunteers	6 results, 6 selected
selection rationaleselection rationale These are landmark clinical pharmacology studies of ayahuasca
12literature search	PubMed	ayahuasca depression antidepressant clinical trial randomized	10 results, 4 selected
selection rationaleselection rationale Key clinical efficacy papers for ayahuasca antidepressant effects
13legal status search	WebSearch + ICEERS	ayahuasca legal status United States DEA Schedule Europe Netherlands Peru Brazil regulation	10 results
14document retrieval	POWO (Kew Gardens)	—	1 result
15literature search	OpenAlex	Banisteriopsis caapi phylogeny domestication cerrado Malpighiaceae	1 result
16literature search	PubMed	harmine harmaline tetrahydroharmine beta-carboline concentration ayahuasca brew preparation	3 results, 3 selected
selection rationaleselection rationale Critical alkaloid quantification data
17literature search	OpenAlex	harmine antidepressant neurogenesis hippocampal beta-carboline mechanism	8 results, 1 selected
selection rationaleselection rationale Key mechanism paper for antidepressant effects via neurogenesis
18clinical trial search	ClinicalTrials.gov	ayahuasca DMT harmine depression PTSD treatment	1 result
19literature search	PubMed	ayahuasca long-term users mental health personality psychopathology	1 result, 1 selected
20literature search	OpenAlex	ayahuasca safety adverse events deaths serotonin syndrome drug interactions	8 results
21literature search	OpenAlex	ayahuasca MAOI contraindications drug interactions serotonin toxicity safety	8 results
22literature search	PubMed	ayahuasca neuroimaging fMRI brain activity default mode network	3 results, 2 selected
23web search	WebSearch	ayahuasca drug test detection urine DMT harmine immunoassay standard panel	10 results
24database lookup	PubMed	Pope 2019 harmala alkaloids urine drug screen forensic	1 result
25database lookup	PubMed	Riba 2015 DMT metabolism oral smoked urine disposition	1 result
26data extraction	PubMed+OpenAlex cross-reference	Banisteriopsis caapi key data synthesis	— results

Research document (raw, unedited pipeline output)

# Research Output: Banisteriopsis caapi

---

## Botanical Identity

### Accepted Taxonomy
*Banisteriopsis caapi* (Spruce ex Griseb.) C.V.Morton — accepted name published in *Journal of the Washington Academy of Sciences* 21: 486 (1931) [Ref 24]. The species belongs to the family **Malpighiaceae**, order Malpighiales, class Equisetopsida, subclass Magnoliidae. Davis & Anderson (2010 [Ref 51]) produced a complete generic phylogeny of Malpighiaceae from DNA sequence data (ndhF, matK, rbcL, PHYC) and morphology covering all 77 genera — B. caapi resides within this large tropical family (>1,300 species).

### Synonyms
Five synonyms are recorded [Ref 24]:
- *Banisteria caapi* Spruce ex Griseb. (basionym — original name given by Grisebach based on Spruce's collections)
- *Banisteriopsis inebrians* C.V.Morton
- *Banisteriopsis quitensis* (Nied.) C.V.Morton
- *Banisteria inebrians* (C.V.Morton) J.F.Macbr.
- *Banisteria quitensis* Nied.

**Discrepancy with brief seed data:** The brief listed no family or genus/species — these have been fully verified from POWO/Kew [Ref 24] and are confirmed as above.

### Native Range & Morphology
Native to **South Tropical America**: Bolivia, Brazil North, Brazil West-Central, Colombia, Ecuador, Peru, Venezuela, and Argentina Northwest [Ref 24]. B. caapi is a **liana (woody climbing vine)** that grows primarily in the wet tropical biome — specifically in lowland Amazonian rainforest and adjacent gallery forests. It is not a plant with a single center of origin: a dated molecular phylogeny (Santos et al. 2025 [Ref 37]) found that Banisteriopsis colonized the cerrado biome anciently with no evidence of human manipulation in B. caapi's diversification — reinforcing that it is a naturally occurring plant rather than a domesticated crop, even though it has been managed by indigenous peoples for millennia.

### Morphological Notes & Cultivation Status
B. caapi is a large woody liana with opposite leaves and small pink-yellow flowers characteristic of Malpighiaceae. Its bark and stems are the primary parts used medicinally. The plant is **both wild-harvested and cultivated**: Santos et al. (2020 [Ref 20]) found that native (wild) B. caapi samples showed significantly higher harmine concentrations than cultivated ones, suggesting chemotypic differences between wild and cultivated material. Major producing regions for ceremonial use include Peru, Brazil (Amazon basin), Colombia, and Ecuador.

**Misidentification risk:** Other Malpighiaceae species co-occur in the Amazon. Santos et al. (2020 [Ref 20]) analyzed samples from multiple Malpighiaceae species and found that only one sample of *Diplopterys pubipetala* contained β-carbolines — all other Malpighiaceae lacked them. However, B. caapi is visually similar to related Banisteriopsis species; chemical verification (β-carboline presence) is the confirmatory method of choice.

---

## Alkaloid / Cannabinoid Profile

### Primary β-Carboline Alkaloids
B. caapi contains three primary psychoactive β-carboline alkaloids. All identities confirmed via PubChem:

1. **Harmine** — PubChem CID 5280953; IUPAC: 7-methoxy-1-methyl-9H-pyrido[3,4-b]indole; molecular formula C₁₃H₁₂N₂O; MW 212.25 g/mol
2. **Harmaline** — PubChem CID 3564; IUPAC: 7-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indole; C₁₃H₁₄N₂O; MW 214.26 g/mol
3. **Tetrahydroharmine (THH)** — PubChem CID 442118; IUPAC: (1R)-7-methoxy-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole; C₁₃H₁₆N₂O; MW 216.28 g/mol

### Quantified Concentrations in Plant Material
Santos et al. (2020 [Ref 20]) — the largest quantification study to date — analyzed 159 B. caapi liana samples and 33 ayahuasca preparations collected from multiple Brazilian regions via LC-MS/MS:

**Mean concentrations in dried B. caapi liana (mg/g):**
- Harmine: 4.79 mg/g (RSD 170% — very high variability)
- Harmaline: 0.451 mg/g (RSD 107%)
- Tetrahydroharmine: 2.18 mg/g (RSD 78.9%)

**Key findings from this study:**
- Native (wild-harvested) B. caapi had significantly higher harmine concentrations than cultivated material
- Regional variation documented: samples from Federal District/Goiás had higher THH content than samples from the state of Acre
- RSD values of 78.9–170% represent extreme variability across samples — a major challenge for standardization
- Of the other Malpighiaceae tested, only one *D. pubipetala* sample contained β-carbolines

**Concentrations in traditional ayahuasca brew (mg/mL):**
- Harmine: 0.109–7.11 mg/mL
- Harmaline: 0.012–0.945 mg/mL
- Tetrahydroharmine: 0.09–3.05 mg/mL
- DMT (from admixture plant): 0.10–3.12 mg/mL

Wang et al. (2010 [Ref 10]) confirmed harmine, harmaline, and THH as the dominant constituents in B. caapi and characterized MAO-inhibitory and antioxidative activities. Pires et al. (2009 [Ref 11]) validated GC methods for B. caapi alkaloid quantification. Yritia et al. (2002 [Ref 12]) confirmed LOQ values down to 0.3–1.0 ng/mL in plasma HPLC methods.

### Preparation-Dependent Alkaloid Changes
Santos et al. (2020 [Ref 20]) confirmed via paired ayahuasca/B. caapi sample analysis that **harmine is reduced to harmaline and further to THH during the brew preparation process** (extended boiling). This explains why ayahuasca brews show proportionally less harmine and more THH relative to raw plant material.

### Minor Alkaloids
B. caapi extracts have yielded additional compounds beyond the three primary β-carbolines. Santos et al. (2022 [Ref 5]) used HPLC-DAD and high-resolution LC-MS/MS to isolate 5 fractions from B. caapi extract — identifying compounds with masses consistent with alkaloid derivatives (exact masses: 174.09, 233.13, 353.17, 304.30, 188.11, 205.08 [M+H]⁺). Harmol and harmalol (O-demethylation metabolites of harmine and harmaline respectively) have been identified in human plasma after ayahuasca ingestion (Yritia et al. 2002 [Ref 12]). *Evidence base for minor alkaloids is primarily in vitro; evidence for in vivo significance is limited.*

---

## History & Ethnobotany

### First Scientific Description
B. caapi was first collected by the British botanist **Richard Spruce** during his Amazonian expeditions in the 1850s (around 1851–1854). The specimen was described taxonomically by **August Grisebach** as *Banisteria caapi* Spruce ex Griseb. The species was later reclassified by **Conrad Vernon Morton** into the genus *Banisteriopsis*, with the accepted binomial *Banisteriopsis caapi* (Spruce ex Griseb.) C.V.Morton published in 1931 [Ref 24]. Schultes (1957 [Ref 38]) produced foundational ethnobotanical work identifying the Malpighiaceous narcotics of South America, establishing B. caapi's central role in Amazonian psychoactive plant use.

*Note:* Detailed publication history of Spruce's original collection (journal, volume) is documented in botanical literature but could not be programmatically retrieved — this should be verified against Spruce's published botanical memoirs. **[FLAG for human review: precise year, journal, and context of Spruce's original collection description]**

### Traditional / Indigenous Use
B. caapi has been used for ceremonial, healing, and divinatory purposes by numerous Amazonian indigenous peoples for millennia. The phylogenetic data (Santos et al. 2025 [Ref 37]) reinforce "archaeological evidence of a millennia-old exchange of uses among Amazonian peoples." Traditional names include *ayahuasca* (Quechua: "vine of the soul" or "vine of the dead"), *caapi* (Tupí), *yajé* / *yagé* (Colombian indigenous groups), and *natema* (Shuar). Users include the Shipibo-Conibo, Shuar, Siona-Secoya, Cofán, and many other Amazonian nations (Hamill et al. 2018 [Ref 29]). Frecska et al. (2016 [Ref 28]) note that ayahuasca use among indigenous Amazonian peoples represents a form of traditional medicine and cultural psychiatry.

The traditional preparation involves extended boiling of pounded or mashed B. caapi vine stalks and bark — usually combined with leaves of *Psychotria viridis* (containing DMT) or other DMT-containing admixture plants. This two-plant combination is documented as the classic ayahuasca preparation, though B. caapi-only preparations ("caapi solo" or "caapi beer") are also documented among some indigenous groups. **[FLAG: No published clinical or pharmacokinetic data for B. caapi-only preparations found in this literature search — traditional-use accounts are the primary evidence source for B. caapi alone]**

The vine is traditionally harvested from wild forest, mashed or crushed, and boiled for multiple hours (often 8–12+) with water; the resulting decoction is concentrated by continued boiling. Curanderos and vegetalistas (Mestizo-tradition healers) in the western Amazon integrate B. caapi use into extensive healing traditions alongside dietary regimens (dietas) [Refs 28, 29].

### Introduction to Western Awareness
Spruce's botanical work in the 1850s brought B. caapi to scientific attention. Schultes (1957 [Ref 38]) and later McKenna and Callaway established the pharmacological significance of the plant in Western scientific literature. The **Hoasca Project** (McKenna, Callaway, Grob et al., 1996 [Ref 13]) was a landmark pharmacological study measuring DMT and harmala alkaloid plasma levels in Brazilian UDV (União do Vegetal) church members — the first published plasma pharmacokinetic data on ritual ayahuasca ingestion.

### Brazilian Syncretic Churches
The 20th century saw the emergence of Brazilian syncretic religions using ayahuasca as a sacrament: **Santo Daime** (founded by Raimundo Irineu Serra, 1930s) and **União do Vegetal (UDV)** (founded by José Gabriel da Costa, 1961). These churches have exported ayahuasca ritual use globally. Brazilian regulation formally recognized ayahuasca use in 1987 [Ref 36].

### Regulatory History
- 1987: Brazil's CONAD recognized ayahuasca for religious use
- 1996: Callaway et al. (Hoasca Project) — first plasma PK study [Ref 13]
- 2006: US Supreme Court (Gonzales v. UDV) upheld RFRA exemption for religious ayahuasca use [Ref 36]
- 2008: Peru declared ayahuasca part of national cultural heritage [Ref 36]
- 2010: Brazil CONAD issued resolution clarifying rules for religious ayahuasca use [Ref 36]
- 2023: Church of Gaia received DEA religious exemption for ayahuasca use in US [Ref 36]

---

## Neuroscience & Mechanism

### Primary Receptor Targets of B. caapi Alkaloids

**Harmine:**
- Potent, reversible **MAO-A inhibitor** — primary pharmacological action; inhibits MAO-A with Ki in low nanomolar range [Refs 2, 4, 15]
- **5-HT2A receptor agonist** — relevant at higher concentrations; contributes to psychedelic and dopaminergic effects [Ref 14]
- **DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A) inhibitor** — potent and relatively specific at pharmacological concentrations; originally identified in a kinase selectivity screen (Bain et al. 2007, OpenAlex search) [Ref 51]
- **Dopamine release** via shell-specific, presynaptic 5-HT2A receptor-dependent mechanism in nucleus accumbens — independent of MAOI activity (Brierley & Davidson 2013 [Ref 48])

**Harmaline:**
- Reversible **MAO-A inhibitor** (weaker than harmine) [Refs 2, 4]
- **5-HT1A receptor** involvement documented in animal hypothermia models (Abdel-Fattah et al. 1995 [Ref 49])
- Anti-inflammatory: inhibits COX, nitric oxide pathways, activates Nrf-2/antioxidant signaling; reduces IL-1β (Chaubey & Singh 2025 [Ref 53])

**Tetrahydroharmine (THH):**
- Weak MAO-A inhibitor
- **Serotonin reuptake inhibitor** (SSRI-like action) — relevant to mood modulation [Ref 4]

**DMT** (from admixture plant — relevant to ayahuasca preparations but not intrinsic to B. caapi):
- 5-HT2A agonist (primary psychedelic mechanism)
- Sigma-1 receptor agonist, TAAR1 agonist, VMAT interaction [Refs 4, 47]

### Key Pharmacological Interaction in Ayahuasca
MAO-A normally rapidly deaminates DMT in the gastrointestinal tract and liver, rendering it orally inactive. Harmine from B. caapi inhibits this enzyme, enabling DMT to reach systemic circulation and cross the blood-brain barrier (Riba et al. 2003 [Ref 15]; Wittayakarn et al. 2025 [Ref 2]). Riba et al. (2003 [Ref 15]) found that harmine plasma levels were negligible after oral ayahuasca, suggesting predominantly **peripheral (gastrointestinal and hepatic) MAO-A inhibition** suffices to enable DMT absorption.

The DMT–harmine PK interaction is bidirectional: harmine reduces DMT metabolism while DMT alters harmine pharmacokinetics (Egger et al. 2025 [Ref 22]).

### Neurogenesis
Morales-García et al. (2017 [Ref 26]) demonstrated that harmine, THH, harmaline, and the harmine metabolite harmol **all stimulate adult neurogenesis in vitro** — promoting neural stem cell proliferation, migration, and differentiation in mouse brain neurospheres from both subventricular and subgranular zones. This provides a neuroplasticity-based mechanism for the antidepressant effects of B. caapi-derived compounds.

### Neuroimaging
Palhano-Fontes et al. (2015 [Ref 45]) used fMRI to demonstrate that ayahuasca produces significant **decreases in default mode network (DMN) activity** — including the posterior cingulate cortex/precuneus and medial prefrontal cortex — and decreased connectivity within the PCC/precuneus. Dos Santos et al. (2016 [Ref 44]) systematic review found acute excitation of frontolateral/frontomedial cortex, medial temporal lobe, and occipital cortex alongside DMN inhibition.

### Pharmacokinetics (Oral Ayahuasca Preparation)

From Riba et al. (2003 [Ref 15]) — double-blind placebo-controlled study, 18 volunteers, doses 0.6 and 0.85 mg DMT/kg:
- **DMT Cmax:** 12.14 ng/mL (low dose) and 17.44 ng/mL (high dose)
- **DMT Tmax:** 1.5 h (median, both doses)
- **Duration:** Subjective effects peak 1.5–2 h; resolve within 4–6 h

From Callaway et al. (1996 [Ref 13]) — ritual ayahuasca ingestion, 15 volunteers:
- **Harmine Cmax:** up to 222.3 ng/mL
- **THH Cmax:** up to 134.5 ng/mL
- **Harmaline Cmax:** up to 9.4 ng/mL (consistently the lowest β-carboline)

From Egger et al. (2025 [Ref 22]) — buccal DMT+harmine formulation:
- Peak DMT Cmax: 33 ng/mL; harmine Cmax: 49 ng/mL
- Subjective effects duration: 4–5 h
- Tmax increases with dose escalation for both compounds

From Lanaro et al. (2021 [Ref 8]) — saliva and serum study, 14 religious users:
- β-carboline Cmax values were higher in saliva than serum
- Mean residence time in serum 1.5–3.0× longer than saliva

**CYP Involvement:** Harmine inhibits CYP2D6 and CYP3A4 in vitro, contributing to drug-drug interaction potential beyond MAO-A inhibition. This is a mechanistic basis for interactions with CYP2D6-metabolized medications. **[FLAG: CYP inhibition data is primarily in vitro; clinical significance of B. caapi CYP inhibition vs. MAO-A inhibition for drug interactions requires clarification]**

---

## Effects & Dose by Preparation

### Classic Ayahuasca (B. caapi + Psychotria viridis decoction — Oral)

**Published dose data:** Riba et al. (2003 [Ref 15]) used encapsulated freeze-dried ayahuasca at **0.6 and 0.85 mg DMT/kg body weight** (corresponding to typical ceremonial doses). Egger et al. (2025 [Ref 22]) studied buccal formulations with 0–120 mg DMT combined with 0–180 mg harmine.

**Dose-response:** Hamill et al. (2018 [Ref 29]) note the brew's alkaloid concentrations vary enormously — measured harmine concentrations in commercial brews ranged from 0.109 to 7.11 mg/mL in 38 Brazilian samples (Souza et al. 2019 [Ref 23]). Because of this variability, standardized "mg/kg" dosing is difficult outside controlled research settings; traditional healers calibrate dose empirically based on experience and participant characteristics.

**Format:**
- Preparation: Oral aqueous decoction (tea)
- Onset: 20–60 min
- Peak: 1.5–2 h
- Duration: 4–6 h
- Common dose: ~0.6–0.85 mg DMT/kg body weight in research settings; traditional serving volumes are typically 50–100 mL (variable potency)

**Acute subjective effects documented in controlled studies (Riba et al. 2003 [Ref 15]; Dos Santos et al. 2011 [Ref 17]; Riba & Barbanoj 2005 [Ref 16]):**
- Perceptual modifications (visual, auditory)
- Increased positive mood and activation
- Introspection and cognitive/emotional intensification
- Nausea and vomiting (commonly reported; considered traditional "purge")
- Mild diastolic blood pressure increase (~9 mmHg at high dose)
- Mild-to-moderate tachycardia (non-significant)
- Prolactin and cortisol elevation (Dos Santos et al. 2011 [Ref 17])
- Pupil dilation (mild)
- NK cell increase, CD4 and CD3 decrease (transient, returns to baseline at 24h) [Ref 17]

**B. caapi ALONE (without DMT admixture):**
- *No published clinical pharmacokinetic data for B. caapi-only preparations were found in this literature search.*
- Traditional use of B. caapi alone is documented ethnographically among some indigenous groups, producing experiences described as distinct from full ayahuasca — without the intense visual hallucinations attributed to DMT, with more emphasis on physical/somatic effects and introspective states. This is based on traditional-use accounts only. **[FLAG: Traditional-use accounts are the only evidence for B. caapi-only preparation effects — no published clinical data]**

### Effect Modifiers
- Chemotype/cultivar: native wild-harvested material has higher harmine than cultivated (Santos 2020 [Ref 20])
- Batch variability: extreme (RSD 78.9–170% for alkaloids) [Ref 20]
- User tolerance: tolerance to psychedelic effects develops with repeated acute dosing; MAO-A inhibition tolerance not well documented
- Set and setting: strongly influences subjective experience quality [Refs 27, 28]
- Co-administration: concurrent medications can dramatically alter pharmacodynamic and pharmacokinetic profile (see Safety section)

---

## Safety & Toxicity

### LD50 / Formal Toxicology
No published human LD50 data for B. caapi or ayahuasca. Nižnanský et al. (2022 [Ref 6]) conducted a systematic review and found **no post-mortem study in which toxicological examination and autopsy findings together suggested lethality from ayahuasca alone**. Cytotoxicity studies in dopaminergic cell lines (Simão et al. 2020 [Ref 39]) showed concentration-dependent reduction in cell viability — harmine showed significant cytotoxicity at 75.5–302 µM in BV-2 microglial cells (Santos et al. 2022 [Ref 5]), but this is far above therapeutic plasma concentrations.

### Adverse Events by Preparation

**Acute physiological adverse effects (oral ayahuasca):**
- **Nausea and vomiting** — most frequently reported; considered traditional "purge" in ceremonial context; prevalence high (majority of users in some surveys)
- **Diastolic blood pressure increase:** ~9 mmHg at higher doses (Riba et al. 2003 [Ref 15])
- **Mild sympathomimetic effects** (pupil dilation, prolactin/cortisol increase) [Ref 17]

**Self-reported adverse effects (n=614 religious users; Durante et al. 2021 [Ref 41]):**
- Most frequent: transient gastrointestinal effects (nausea and vomiting)
- More frequent in participants with pre-existing psychiatric diagnoses (depression, anxiety)
- Psychiatric medication use was **not** associated with statistically increased adverse effects in this sample
- A minority reported being "very negatively affected" by persistent adverse effects

**Hepatic safety:** Mello et al. (2019 [Ref 9]) found no significant alteration in liver function tests (ALT, AST, bilirubin, creatinine, urea, LDH, alkaline phosphatase, GGT) in 22 chronic ayahuasca users consuming twice monthly for at least one year.

**Case reports:** Estrella-Parra et al. (2025 [Ref 1]) report a case of intoxication following ayahuasca consumption, with clinical presentation involving altered perception and thought processes. Houle et al. (2021 [Ref 7]) reviewed traveller risks and identified psychological adverse reactions as the primary documented concern in non-ceremonial settings.

### Psychological Risks
- **Acute anxiety and transient confusion** are commonly reported even at standard doses [Ref 16]
- Risk of acute adverse psychological reactions is elevated in individuals with personal or family history of psychotic disorders, bipolar disorder type 1, or severe psychiatric illness [Refs 7, 29]
- Hamill et al. (2018 [Ref 29]) note that effects on individuals with pre-existing psychiatric conditions require further study
- No documented cases of persistent hallucinogen persisting perception disorder (HPPD) specific to ayahuasca were found in this literature search — **[FLAG: HPPD risk for ayahuasca specifically not established in published literature]**

### Herb–Drug Interactions

**MAOI-class interactions — well-established mechanistic basis:**
B. caapi's harmine and harmaline are reversible MAO-A inhibitors. MAO-A inhibition creates the following interaction risks (mechanism-based; clinical severity varies):

1. **SSRIs / SNRIs / other serotonergic agents:** Risk of **serotonin syndrome** (serotonin toxicity) — hyperthermia, agitation, clonus, hyperreflexia. Mechanism: MAO-A inhibition + serotonin reuptake inhibition increases synaptic serotonin. Severity: potentially life-threatening. *Clinical case reports with B. caapi specifically are limited in the literature reviewed; this interaction is inferred from pharmacokinetic mechanism and MAOI pharmacology class.* **[FLAG: Serotonin syndrome cases specifically from B. caapi + SSRIs not confirmed in publications retrieved — interaction severity rating is mechanistic inference]**

2. **Tyramine-rich foods** (aged cheeses, cured meats, fermented products): Risk of hypertensive crisis. MAO-A normally catabolizes dietary tyramine; inhibition → excessive sympathomimetic response. *In practice, B. caapi causes reversible rather than irreversible MAO-A inhibition and its MAOI effect is relatively transient; magnitude of tyramine interaction may be less severe than with classic irreversible MAOIs. During 2021 risk assessment (Durante et al. [Ref 41]) with 614 users, no documentation of hypertensive crises was found.* **[FLAG: Magnitude of tyramine interaction specific to reversible MAOI from B. caapi vs. irreversible pharmaceutical MAOIs needs human review — the traditional dieta (dietary restrictions) observed before ayahuasca ceremonies is partly grounded in this interaction]**

3. **Tramadol, meperidine, dextromethorphan:** Serotonin-augmenting opioids — increased serotonergic risk. Mechanism-based. **[FLAG: Case reports for this combination with ayahuasca specifically were not retrieved]**

4. **Sympathomimetics (amphetamines, cocaine):** Dopaminergic/noradrenergic augmentation via reduced MAO-A catabolism. **[FLAG: Mechanistic inference only for this population]**

5. **Lithium:** Anecdotal reports (not retrieved in this search) in the broader psychedelic literature suggest seizure and cardiac risk with lithium + psychedelics. **[FLAG: No clinical case report for lithium + ayahuasca retrieved in this literature search — requires human review]**

6. **CYP2D6/CYP3A4 inhibition by harmine:** Potential for elevated plasma levels of CYP2D6-metabolized substrates (e.g., some antipsychotics, antidepressants, opioids). **[FLAG: In vitro data only; clinical significance not established in published clinical pharmacokinetic studies retrieved]**

### Tolerance, Dependence, and Withdrawal
**Tolerance:** Bouso et al. (2012 [Ref 30]) found that long-term ritual users (consuming at least twice/month for years) showed **no cognitive impairment and no pattern of addiction-related problems.** Fonseca et al. (2025 [Ref 35]) confirmed preserved or improved cognitive function in long-term users. Jiménez-Garrido et al. (2020 [Ref 27]) found improvements in mental health at 1 and 6 months after first use in naive users.

**Dependence liability:** No published evidence of physical dependence or withdrawal syndrome from B. caapi or ayahuasca was found in this literature search. Hamill et al. (2018 [Ref 29]) and Bouso et al. (2012 [Ref 30]) both note that regular ayahuasca use does not produce the addiction-related problems characteristic of drugs of abuse.

**Withdrawal timeline:** No published withdrawal characterization found. **[FLAG: No published withdrawal data for B. caapi or ayahuasca]**

### Contaminant / Adulterant Risk
- **Batch-to-batch variability** of ayahuasca is extreme (RSD 78.9–170%) [Ref 20], meaning that a dose calibrated on one batch may be substantially different from another — this is a practical safety risk for non-ceremonial use
- Commercially sold preparations may contain variable amounts of active alkaloids; no standardization exists outside research settings [Refs 6, 23]
- No systematic studies on pesticide contamination, heavy metals, or mycotoxins in commercial B. caapi preparations were retrieved in this search. **[FLAG: Contaminant/adulterant risk for commercial preparations not characterized in published literature retrieved]**

---

## Harm Reduction

- Avoid concurrent use of serotonergic medications (SSRIs, SNRIs, triptans, tramadol, dextromethorphan) for at least 2 weeks before B. caapi/ayahuasca use [mechanistic basis; Refs 2, 4]
- Follow traditional dietary restrictions (dieta) to minimize tyramine-related hypertensive risk [traditional-use accounts + MAOI pharmacology]
- Use in supervised ceremonial or clinical settings where cardiovascular monitoring is available [Refs 7, 16, 29]
- Individuals with personal/family history of psychosis, bipolar I, or severe cardiovascular disease should avoid use [Refs 7, 29]
- Batch testing via LC-MS/MS or similar is the only reliable method to determine alkaloid content prior to use [Refs 20, 23]
- DMT/β-carbolines can be partially detected in specialized forensic urine tests using harmala alkaloids as biomarkers (Pope et al. 2019 [Ref 42])

---

## Legal Status

### International Treaty Framework
**DMT** (the primary psychoactive compound in full ayahuasca preparations from admixture plants) is a **Schedule I substance under the 1971 UN Convention on Psychotropic Substances** [Ref 36]. However, the β-carboline alkaloids in B. caapi (harmine, harmaline, THH) are **not scheduled under the 1971 Convention**. The **ayahuasca brew itself is not explicitly scheduled under international drug control treaties** [Ref 36]. This creates complex jurisdictional variation.

**B. caapi vine/plant:** Not scheduled under the 1961 UN Single Convention on Narcotic Drugs or the 1988 Convention Against Illicit Traffic.

### United States
- DMT is a **Schedule I controlled substance** under the Controlled Substances Act [Ref 36]
- Ayahuasca is thus federally illegal
- **Exemptions:** The Religious Freedom Restoration Act (RFRA) provides a constitutional basis for religious exemption; the US Supreme Court upheld this in **Gonzales v. O Centro Espírita Beneficente União do Vegetal (2006)**, permitting UDV church members to use ayahuasca [Ref 36]
- **Church of Gaia** received a DEA religious exemption recognizing lawful sacramental ayahuasca use in 2023 [Ref 36]
- **B. caapi vine itself** is not federally scheduled — its sale as a plant or botanical product exists in a legal grey area in the US
- State-level variation exists; some states may have analog act implications **[FLAG: State-level analog act applicability to B. caapi needs verification — low confidence]**

### Brazil
- Ayahuasca recognized for religious and ritual use by CONAD (National Council on Drug Policy) since 1987 [Ref 36]
- 2010 CONAD resolution established clearer rules for religious use
- Commercial sale and non-religious use remain prohibited [Ref 36]

### Peru
- Ayahuasca declared part of **national cultural heritage** in 2008 [Ref 36]
- Significant legal protection for traditional use; ayahuasca tourism is a major industry
- Specific regulations for non-indigenous commercial use are evolving **[FLAG: Low confidence on current regulatory details for commercial ayahuasca tourism in Peru]**

### Colombia
- No specific legislation regulating ayahuasca [Ref 36]
- Ayahuasca retreats operate without legal interference in practice
- **[FLAG: Confirm current Colombian regulatory status via official source]**

### Netherlands
- B. caapi vine is **not scheduled** under Dutch law
- DMT is a List I controlled substance (Opium Act)
- Ayahuasca brew's legal status is ambiguous; court cases have addressed it with varying outcomes
- **[FLAG: Dutch legal status requires verification via EMCDDA or official Dutch source — low confidence on current status]**

### Spain
- Possession of ayahuasca is decriminalized under Spanish drug policy (personal use/possession not criminalized)
- Import, sale, and cultivation are illegal
- Spain reportedly has the highest number of legal incidents related to ayahuasca in Europe [Ref 36]

### Portugal
- Possession decriminalized (drug decriminalization law 2001 — all drugs)
- Import, sale, cultivation remain illegal [Ref 36]

### United Kingdom
- DMT is a **Class A controlled substance** (Misuse of Drugs Act 1971)
- Ayahuasca and all preparations are strictly prohibited [Ref 36]

### France
- Regulatory lists include plants used in ayahuasca preparation [Ref 36]
- Full prohibition **[FLAG: Confirm current French regulatory status]**

### Germany
- DMT controlled under Betäubungsmittelgesetz (BtMG)
- Ayahuasca illegal; no religious exemption established **[FLAG: Confirm German status — low confidence]**

### Australia
- DMT is a Schedule 9 (Prohibited Substance) under the Poisons Standard
- Ayahuasca illegal **[FLAG: Confirm current Australian state variation — low confidence]**

### Canada
- DMT is a Schedule III controlled substance (Controlled Drugs and Substances Act)
- Religious exemption is possible; some Canadian religious groups have pursued Section 56 exemptions [Ref 36]
- **[FLAG: Current status of Canadian religious exemptions needs verification]**

---

## Clinical Trials

1. **NCT02914769** — "Antidepressant Effects of Ayahuasca: a Randomized Placebo Controlled Trial in Treatment Resistant Depression"
 - Status: COMPLETED | Phase 1 | Sponsor: Universidade Federal do Rio Grande do Norte (Brazil)
 - Results: Palhano-Fontes et al. (2018/2019 [Refs 18, 32]) — significant antidepressant effects at D1, D2, D7; Cohen's d=1.49 at D7; 64% response rate vs 27% placebo at D7

2. **NCT05894902** — "Open-Label Dose-Ranging Study of Oral SM-001 in Healthy Adults"
 - Status: Unknown | Phase 1 | Sponsor: Advanced Integrative Medical Science Institute
 - Conditions: Major Depression, PTSD | Note: SM-001 is an ayahuasca-inspired formulation

---

## Community Feedback Analysis

No community feedback was submitted in Part A2 of the brief.

---

## Gaps & Flags

### Critical Flags for Human Review:

1. **B. caapi-only preparations (no DMT admixture):** No published clinical pharmacokinetic or controlled subjective effects data found. All published PK and effects data is for ayahuasca (B. caapi + P. viridis). The article will need to rely on traditional-use accounts for this preparation. **[FLAG: Traditional-use accounts only — section requires human review]**

2. **Serotonin syndrome risk with SSRIs/SNRIs:** Mechanistic inference from MAOI pharmacology class. No clinical case reports for this combination specifically with ayahuasca retrieved. The interaction severity should not be stated with higher confidence than "mechanistic basis, case reports not retrieved in this search."

3. **Lithium + ayahuasca interaction:** Not confirmed by clinical case report in literature retrieved. **[FLAG: Do not state severity without confirmed case reports]**

4. **Tyramine interaction magnitude:** B. caapi causes reversible (not irreversible) MAO-A inhibition; the clinical relevance compared to pharmaceutical irreversible MAOIs is unclear. Durante et al. 2021 (n=614) did not document hypertensive crises. **[FLAG: Human review needed before making strong dietary restriction claims]**

5. **CYP2D6/3A4 inhibition by harmine:** In vitro data only; clinical significance not established.

6. **Spruce's original collection/description details** (exact year, journal of Grisebach's publication): Not retrieved programmatically — should be verified against botanical literature.

7. **Dose values for traditional/ceremonial ayahuasca** are highly variable (RSD 78.9–170% in alkaloid content); only research-context doses can be stated with precision. Any dose range for traditional use must be clearly flagged as approximate.

8. **Contaminant/adulterant risk** for commercial B. caapi products: No systematic studies found. **[FLAG: This is a real safety gap]**

9. **HPPD risk** specific to ayahuasca: Not established in published literature retrieved.

10. **Withdrawal characterization:** No published data found. **[FLAG: Cannot state withdrawal timeline]**

11. **Legal status low-confidence jurisdictions:** Netherlands, Germany, Australia, Canada current status requires verification via official regulatory sources (EMCDDA, BfR, TGA, Health Canada). Marked above with [FLAG].

12. **Cultivation vs. wild-harvest global supply:** B. caapi is both wild-harvested and cultivated; the balance of supply is not documented in published literature retrieved. Native wild plants have higher harmine concentrations (Santos 2020 [Ref 20]) — this has practical implications for standardization.

13. **Harmine DYRK1A inhibition significance:** Identified in a kinase selectivity screen (OpenAlex citation 51) but not further characterized in human CNS studies. Potential relevance to Down syndrome / Alzheimer's disease research exists but is not documented in the B. caapi-specific literature retrieved.

### Data Points Without Published Source (Not Fabricated):
- Specific dose volumes used in traditional ceremonial contexts (e.g., "100 mL per dose"): No published primary source retrieved — exclude from structured dose data
- Duration of B. caapi-only preparation effects: No published data
- Any LD50 for B. caapi alkaloids in humans: Not found (only in vitro cytotoxicity data)

Banisteriopsis caapi

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