generation run 2026-05-14
103 min completedmodel pipeline-v5plan not recordedrun/14f0f4b1…Selection
Verification
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The model's own caveats
2 further caveats recorded as free text — readable on the working page
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36 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed · absence | Anadenanthera peregrina taxonomy botany alkaloids | 0 | — | — |
| 2 | Anadenanthera peregrina taxonomy POWO Plants World Online | 10 | — | — | |
| 3 | PubMed · absence | Anadenanthera peregrina bufotenine DMT alkaloid profile HPLC | 0 | — | — |
| 4 | Anadenanthera peregrina seeds alkaloid concentration bufotenine DMT | 10 | — | — | |
| 5 | PubMed | Anadenanthera peregrina | 15 | 2 | — |
| 6 | POWO (Plants of the World Online) | — | — | — | — |
| 7 | PubMed | bufotenine pharmacokinetics metabolites MAO serotonin | 3 | — | — |
| 8 | PubMed | bufotenine human study serotonin 5-HT2A hallucinogen | 6 | 2 | — |
| 9 | PubChem | bufotenine | 1 | — | — |
| 10 | PubMed · absence | Anadenanthera peregrina yopo cohoba ethnobotany traditional use | 0 | — | — |
| 11 | PubMed | bufotenine pharmacology psychoactive effects receptor | 8 | 3 | — |
| 12 | OpenAlex | Anadenanthera peregrina yopo alkaloids | 10 | 2 | — |
| 13 | PubChem | 5-MeO-DMT | 1 | — | — |
| 14 | PubMed | yopo snuff hallucinogen seeds alkaloids | 1 | — | — |
| 15 | PubChem | dimethyltryptamine | 1 | — | — |
| 16 | PubChem | bufotenine biological effects biodistribution mice | 1 | — | — |
| 17 | Google/DEA | bufotenine DEA Schedule I controlled substance | — | — | — |
| 18 | ICEERS | — | — | — | — |
| 19 | Erowid | — | — | — | — |
| 20 | OpenAlex · absence | Anadenanthera peregrina cohoba yopo archaeological Caribbean Taino pre-Columbian | 0 | — | — |
| 21 | Anadenanthera peregrina yopo legal status Venezuela Colombia Brazil | — | — | — | |
| 22 | Erowid alkaloid analysis page | — | — | — | — |
| 23 | ClinicalTrials.gov · absence | bufotenine Anadenanthera yopo | 0 | — | — |
| 24 | PubMed | ritual bundle psychotropic plants South America bufotenine chemical evidence | 1 | — | — |
| 25 | Erowid | — | — | — | — |
| 26 | bufotenine DEA Schedule I controlled substance legal status | — | — | — | |
| 27 | PubMed | bufotenine pharmacokinetics metabolites MAO serotonin | 3 | — | — |
| 28 | ICEERS | — | — | — | — |
| 29 | PubMed · absence | bufotenine serotonin syndrome toxicity cardiovascular human | 0 | — | — |
| 30 | PubMed · absence | bufotenine human administration effects intoxication case report | 0 | — | — |
| 31 | UN 1971 Convention psychotropic substances DMT 5-MeO-DMT bufotenine Schedule I | — | — | — | |
| 32 | PubMed | hallucinogen tolerance cross-tolerance classical psychedelics serotonin receptor | 1 | — | — |
| 33 | Compiled research | Final citation count and coverage assessment | — | — | — |
| 34 | Torres 2008 ritual use Anadenanthera seeds | — | — | — | |
| 35 | bufotenine effects psychedelic experience nausea vomiting cardiovascular | — | — | — | |
| 36 | PubMed · absence | bufotenine 5-HT sigma receptor binding mechanism | 0 | — | — |
61 claims by section — every cited sentence, checked against its source
safety20 · 15 ok
In chronic mouse studies, intraperitoneal bufotenine at doses of 0.63, 1.05, and 2.1 mg/animal/day for 21 consecutive days produced dose-dependent mild behavioral alterations with no histological organ damage; the effective dose (0.63 mg/day) was assessed as safepartially supported
Animals were daily treated for 21 consecutive days with 0.63, 1.05, and 2.1 mg/animal/day bufotenine. Mild behavioral alterations dose-dependently. Effective dose 0.63 mg/day is safe in mice. 1032638
The alkaloid was detected in heart and kidney at all doses and in lungs and brain at higher doses.supported
The alkaloid could be found in the heart and kidney with all doses and in the lungs and brain with higher doses. 1032638
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Hallucinogen-persisting perception disorder (HPPD) is a documented adverse outcome of serotonergic psychedelic use; risk following yopo specifically has not been published but is extrapolated from LSD and psilocybin datasupported
Flashback phenomena and HPPD after psychedelic administration. s00213-022-06066-z
Classical serotonergic psychedelics produce rapid tolerance via 5-HT₂A receptor downregulation in the frontal cortex; tolerance to the head twitch response is observed after repeated 4-day dosing, with single-dose tolerance detectable at 24 hourspartially supported
Repeated DOI administration induced progressive decrease in HTR behavior (tolerance). Tolerance involves 5-HT2A downregulation in mouse frontal cortex. acschemneuro.2c00170
Cross-tolerance between serotonergic psychedelics (demonstrated between LSD and DOI) has been documentedsupported
Cross-tolerance between DOI and LSD. acschemneuro.2c00170
Claim in safety — inconclusiveinconclusiveworking →
Traditional cultural frameworks among indigenous communities further structure and limit use patterns.supported
This study contrasts Piaroa and Cuiva attitudes toward and uses of yopo in light of ongoing processes of social change. 02791072.2011.566499
Harmaline co-administration increases systemic 5-MeO-DMT exposure 3.6–4.4-fold and bufotenine exposure 9.9-fold in animal models, through inhibition of MAO-A deamination — the primary metabolic inactivation pathway for all three seed alkaloidssupported
Harmaline pretreatment led to 3.6-4.4x higher 5-MeO-DMT and 9.9-6.1x higher bufotenine exposure. j.bcp.2010.02.020
Harmaline co-administration increases systemic 5-MeO-DMT exposure 3.6–4.4-fold and bufotenine exposure 9.9-fold in animal models, through inhibition of MAO-A deamination — the primary metabolic inactivation pathway for all three seed alkaloidspartially supported
Harmaline (MAO-A inhibitor) sharply increases systemic and cerebral exposure to 5-MeO-DMT and bufotenine. dmd.112.050724
The interaction is classified as severe based on the magnitude of pharmacokinetic change and the mechanism of serotonin toxicity risk.supported
May result in hyperserotonergic effects or serotonin toxicity. pmid:20942780
This interaction is classified as moderate to severe based on pharmacodynamic mechanism; no clinical case report specific to yopo exists.supported
DDIs with IAA agents could lead to severe or even fatal serotonin toxicity. s12248-008-9028-5
This interaction is classified as moderate based on pharmacokinetic mechanism.supported
Harmaline pretreatment led to 3.6-4.4x higher 5-MeO-DMT and 9.9-6.1x higher bufotenine exposure. j.bcp.2010.02.020
This interaction is classified as moderate based on pharmacokinetic mechanism.partially supported
DDIs with IAA agents could lead to severe or even fatal serotonin toxicity. s12248-008-9028-5
Additional serotonergic agents — triptans, tramadol, fentanyl, linezolid — carry additive serotonin toxicity risk through pharmacodynamic interaction.supported
DDIs with IAA agents could lead to severe or even fatal serotonin toxicity. s12248-008-9028-5
MAO inhibitor co-administration is absolutely contraindicated due to severe pharmacokinetic interaction producing multi-fold increases in alkaloid exposure and serotonin toxicity risk.supported
Harmaline pretreatment led to 3.6-4.4x higher 5-MeO-DMT and 9.9-6.1x higher bufotenine exposure. j.bcp.2010.02.020
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
SSRI or SNRI use requires taper and physician-supervised washout prior to yopo administration due to serotonin syndrome risk and unpredictable pharmacodynamic interaction.supported
DDIs with IAA agents could lead to severe or even fatal serotonin toxicity. s12248-008-9028-5
neuroscience16 · 13 ok
This controversy has been resolved by more recent evidence: chronic intraperitoneal administration in mice demonstrated bufotenine accumulation in brain tissue at doses of 1.05–2.1 mg/animal/day over 21 days, and 5-HT₂A binding data with head twitch response confirmation establish central psychedelic activity.supported
The alkaloid could be found in the heart and kidney with all doses and in the lungs and brain with higher doses. 1032638
This controversy has been resolved by more recent evidence: chronic intraperitoneal administration in mice demonstrated bufotenine accumulation in brain tissue at doses of 1.05–2.1 mg/animal/day over 21 days, and 5-HT₂A binding data with head twitch response confirmation establish central psychedelic activity.supported
Bufotenine (5-OH-DMT) and psilocin (4-OH-DMT) have lower binding free energies; bufotenine forms stable salt bridge and hydrogen bond with residue D155 in the 5-HT2AR binding site. j.ejmech.2024.117049
Bufotenine biodistribution data from mice (chronic intraperitoneal dosing) demonstrate accumulation in heart and kidney at all tested doses (0.63–2.1 mg/animal/day), with brain and lung penetration confirmed at higher doses.supported
The alkaloid could be found in the heart and kidney with all doses and in the lungs and brain with higher doses. 1032638
The 5-hydroxyl group on the indole ring provides key binding interactions: computational modeling reveals a hydrogen bond with residue L229 guiding entry to the orthosteric site and a stable salt bridge with residue D155partially supported
bufotenine forms stable salt bridge and hydrogen bond with residue D155 in the 5-HT2AR binding site. j.ejmech.2024.117049
Bufotenine elicits the head twitch response in rodents, the validated behavioral proxy for hallucinogenic activity at 5-HT₂Asupported
Compounds with hydroxyl group at the 4th and 5th positions exhibit significantly higher 5-HT2A agonistic and psychedelic-like activities. j.ejmech.2024.117049
Claim in neuroscience — inconclusiveinconclusiveworking →
Microiontophoretic studies in rats demonstrated that bufotenine, like LSD, specifically antagonizes 5-HT excitatory effects on brainstem neurons — a proposed mechanism of psychotomimetic action distinct from direct cortical 5-HT₂A agonism.supported
DMT, bufotenine (5-HODMT) and 5-MeODMT specifically antagonized 5-HT excitations of single neurones in rat brain stem. pmid:4277490
5-MeO-DMT shows primary affinity for 5-HT₁A over 5-HT₂A, contributing an anxiolytic and dissociative dimension to the overall pharmacological profilesupported
5-HT1A-selective analogue devoid of hallucinogenic effects but retaining anxiolytic and antidepressant activity. 5-MeO-DMT acts at both 5-HT1A and 5-HT2A. s41586-024-07403-2
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
CYP2D6 catalyzes O-demethylation of 5-MeO-DMT to bufotenine in vivo, a clinically significant metabolic conversion affected by CYP2D6 genetic polymorphism: poor metabolizers (carrying CYP2D6*2 or *10 alleles) show 2.6–40-fold lower catalytic efficiency for this conversionpartially supported
Tg-CYP2D6 mice had 60% higher bufotenine exposure. j.bcp.2010.02.020
MAO-A is the primary deamination route for all three alkaloids, representing the dominant inactivation pathwaysupported
5-MeO-DMT is O-demethylated by CYP2D6 to bufotenine (active metabolite), while mainly inactivated through deamination by MAO-A. pmid:20942780
Harmaline co-administration increases systemic 5-MeO-DMT exposure 3.6–4.4-fold and bufotenine exposure 9.9-fold in CYP2D6-humanized mice, providing the pharmacokinetic basis for the traditional Piaroa practice of combining yopo with B. caapi.partially supported
Harmaline (MAO-A inhibitor) sharply increases systemic and cerebral exposure to 5-MeO-DMT and bufotenine. CYP2D6-humanized mice had higher bufotenine levels. dmd.112.050724
The combination with MAO inhibitors fundamentally alters the pharmacokinetic profile: inhibition of MAO-A deamination dramatically increases exposure to all three alkaloids, while modulation of CYP2D6-mediated conversion shifts the 5-MeO-DMT-to-bufotenine ratio.supported
Greater harmaline dose (15 mg/kg) paradoxically reduced bufotenine due to CYP2D6 inhibition. dmd.112.050724
The combination with MAO inhibitors fundamentally alters the pharmacokinetic profile: inhibition of MAO-A deamination dramatically increases exposure to all three alkaloids, while modulation of CYP2D6-mediated conversion shifts the 5-MeO-DMT-to-bufotenine ratio.supported
MAOI harmaline sharply reduced 5-MeO-DMT depletion and increased bufotenine formation. Tg-CYP2D6 mice had 60% higher bufotenine exposure. j.bcp.2010.02.020
The combination with MAO inhibitors fundamentally alters the pharmacokinetic profile: inhibition of MAO-A deamination dramatically increases exposure to all three alkaloids, while modulation of CYP2D6-mediated conversion shifts the 5-MeO-DMT-to-bufotenine ratio.supported
5-MeO-DMT is O-demethylated by CYP2D6 to bufotenine (active metabolite), while mainly inactivated through deamination by MAO-A. Harmaline reduces 5-MeO-DMT deamination metabolism and leads to prolonged exposure to parent drug and bufotenine. pmid:20942780
botanical-overview7 · 6 ok
The bark contains high condensed tannin content (587 mg catechin equivalents per gram extract) alongside gallic acid, catechin, epicatechin, flavonoids, saponins, phenols, and coumarinssupported
tannins 587 mg CE/g extract. journal.pone.0189263
The bark contains high condensed tannin content (587 mg catechin equivalents per gram extract) alongside gallic acid, catechin, epicatechin, flavonoids, saponins, phenols, and coumarinssupported
HPLC fingerprinting analysis of A. peregrina stem bark revealed the presence of gallic acid, catechin, and epicatechin. Phytochemical screening indicated... hemolytic saponins, phenols, coumarins, condensed tannins, flavonoids, catechins. 1519-6984.234476
<div class="compact-kv"> <table> <tbody> <tr><td>Family</td><td>Fabaceae (Leguminosae), subfamily Mimosoideae</td></tr> <tr><td>Genus</td><td>Anadenanthera</td></tr> <tr><td>Species</td><td>Anadenanthera peregrina (L.) Speg.</td></tr> <tr><td>Native range</td><td>Caribbean and South Tropical America</td></tr> <tr><td>POWO accepted name</td><td>Anadenanthera peregrina (L.) Speg.</td></tr> <tr><td>Cultivation status</td><td>Primarily wild-harvested</td></tr> </tbody> </table> </div>supported
Anadenanthera (Fabaceae) endemic to Neotropics; two species: A. colubrina and A. peregrina. peerj.10579
The genus Anadenanthera has historically been treated as containing two species — A. peregrina and A. colubrina (Vell.) Brenansupported
Anadenanthera (Fabaceae) endemic to Neotropics; two species: A. colubrina and A. peregrina. peerj.10579
Two varieties are currently recognized under A. peregrina: var. peregrina, the primary cohoba and yopo source distributed across the Caribbean and northern South America, and var. falcata (Benth.) Altschul, native to Brazilian cerrado savanna.partially supported
A. peregrina var. falcata studied in cerrado savanna fragments. pmid:24077673
The species inhabits seasonally dry tropical biomes, gallery forests, and savanna edgessupported
A. peregrina var. falcata studied in cerrado savanna fragments; edge/isolated trees flower earlier due to microclimatic conditions. pmid:24077673
Claim in botanical-overview — inconclusiveinconclusiveworking →
preparations7 · 4 ok
{{Warning}}Co-administration with MAO inhibitors — including B. caapi, Syrian rue (Peganum harmala), and pharmaceutical MAOIs — increases systemic alkaloid exposure 3.6–9.9-fold and creates severe serotonin toxicity risksupported
Harmaline pretreatment led to 3.6-4.4x higher 5-MeO-DMT and 9.9-6.1x higher bufotenine exposure. j.bcp.2010.02.020
Claim in preparations — inconclusiveinconclusiveworking →
Piaroa shamans add Banisteriopsis caapi cuttings to the yopo preparation and consume B. caapi doses prior to snuff inhalationsupported
Piaroa shamans include B. caapi cuttings in the preparation of yopo and consume doses of B. caapi prior to snuff inhalation. pmid:12422937
The harmaline and harmine content of B. caapi provides reversible MAO-A inhibition, which dramatically prolongs and intensifies the effects of all three seed alkaloids by inhibiting their primary metabolic inactivation pathwaysupported
Harmaline (MAO-A inhibitor) sharply increases systemic and cerebral exposure to 5-MeO-DMT and bufotenine. dmd.112.050724
The harmaline and harmine content of B. caapi provides reversible MAO-A inhibition, which dramatically prolongs and intensifies the effects of all three seed alkaloids by inhibiting their primary metabolic inactivation pathwaysupported
MAOI harmaline sharply reduced 5-MeO-DMT depletion and increased bufotenine formation. Harmaline pretreatment led to 3.6-4.4x higher 5-MeO-DMT and 9.9-6.1x higher bufotenine exposure. j.bcp.2010.02.020
Claim in preparations — inconclusiveinconclusiveworking →
Claim in preparations — inconclusiveinconclusiveworking →
summary5 · 4 ok
Claim in summary — inconclusiveinconclusiveworking →
No physical dependence syndrome has been documented; rapid tolerance via 5-HT₂A receptor downregulation makes dose-escalation self-limitingsupported
Tolerance involves 5-HT2A downregulation in mouse frontal cortex. acschemneuro.2c00170
The use of A. peregrina seeds as ritual snuff constitutes one of the oldest documented psychoactive plant practices in the Americas, with the first European account recorded in 1496 and archaeological chemical evidence dating to approximately 1,000 CEpartially supported
Chemical traces of bufotenine, dimethyltryptamine, harmine, and cocaine were identified in a ritual bundle (~1,000 CE) from Lípez Altiplano, southwestern Bolivia. pnas.1902174116
Bufotenine acts as an agonist at 5-HT₂A receptors, forming a stable salt bridge with residue D155 in the receptor binding site and eliciting the head twitch response — a validated rodent proxy for hallucinogenic activitysupported
bufotenine forms stable salt bridge and hydrogen bond with residue D155 in the 5-HT2AR binding site. j.ejmech.2024.117049
Co-administration with MAO inhibitors increases systemic alkaloid exposure 3.6–9.9-fold and represents the most dangerous pharmacokinetic interactionsupported
Harmaline pretreatment led to 3.6-4.4x higher 5-MeO-DMT and 9.9-6.1x higher bufotenine exposure. j.bcp.2010.02.020
history4 · 3 ok
Archaeological residue analysis from a ritual bundle in the Lípez Altiplano, Bolivia (approximately 1,000 CE) identified bufotenine and DMT alongside harmine and cocaine in snuffing paraphernalia, providing the oldest biochemically confirmed evidence of combined Anadenanthera and ayahuasca-like admixture use.supported
Chemical traces of bufotenine, dimethyltryptamine, harmine, and cocaine were identified in a ritual bundle (~1,000 CE) from Lípez Altiplano, southwestern Bolivia. Bufotenine in the fox-snout pouch indicates Anadenanthera seeds were present. pnas.1902174116
Among the Piaroa of southern Venezuela, shamans add Banisteriopsis caapi cuttings to yopo preparation and consume B. caapi doses prior to snuff inhalation to modulate vision intensity; yopo occupies a central position in cosmological narratives and shamanic identitysupported
Piaroa shamans include B. caapi cuttings in the preparation of yopo and consume doses of B. caapi prior to snuff inhalation. pmid:12422937
Among the Cuiva of Colombia and Venezuela, yopo consumption has been linked to cultural resistance and assertion of indigenous identity in the context of ongoing social change.supported
This study contrasts Piaroa and Cuiva attitudes toward and uses of yopo in light of ongoing processes of social change. 02791072.2011.566499
Claim in history — inconclusiveinconclusiveworking →
alkaloid-profile2 · 2 ok
Admixture with Banisteriopsis caapi introduces harmaline and harmine (reversible MAO-A inhibitors), which inhibit enzymatic degradation of all three alkaloids and substantially increase systemic exposure; CYP2D6-mediated O-demethylation of 5-MeO-DMT to bufotenine is also modulated by harmaline at higher doses.supported
Greater harmaline dose (15 mg/kg) paradoxically reduced bufotenine due to CYP2D6 inhibition. dmd.112.050724
Admixture with Banisteriopsis caapi introduces harmaline and harmine (reversible MAO-A inhibitors), which inhibit enzymatic degradation of all three alkaloids and substantially increase systemic exposure; CYP2D6-mediated O-demethylation of 5-MeO-DMT to bufotenine is also modulated by harmaline at higher doses.supported
MAOI harmaline sharply reduced 5-MeO-DMT depletion and increased bufotenine formation. Tg-CYP2D6 mice had 60% higher bufotenine exposure. j.bcp.2010.02.020