Anadenanthera peregrina

'''Yopo''' (''Anadenanthera peregrina'', Fabaceae) — cohoba, paricá — is a neotropical tree whose seeds produce one of the highest natural concentrations of the [[substance_class:chemical/tryptamine]] alkaloid bufotenine. Its dominant alkaloid, bufotenine, is a classical serotonergic [[substance_class:psychoactive/psychedelic]] active at [[glossary:5-ht2a]] [[glossary:receptor|receptors]]{{cite|doi=10.1016/j.ejmech.2024.117049|anchor=ac47bd20}}. Bufotenine produces its principal effects by agonizing 5-HT₂A receptors in the [[glossary:cortex]], generating intense visual [[glossary:hallucination|hallucinations]] and cognitive [[glossary:disruption]]. Yopo snuff use was first documented by Europeans in 1496 on Hispaniola{{cite|name=pane-1496|type=book|author=Pane R|year=1496|title=Relación acerca de las antigüedades de los indios|anchor=3cdd8258}}, with archaeological chemical evidence dating to approximately 1,000 CE{{cite|doi=10.1073/pnas.1902174116|anchor=d2f9f279}}. Ritual snuff traditions spread across the Caribbean and Orinoco basin, embedded in indigenous healing and cosmological practice. No clinical trials have been registered for yopo or bufotenine; bufotenine remains [[glossary:schedule-i]] in the United States. [[index:effects|Subjective effects]] include intense geometric visuals, [[effect:ego-dissolution]], cognitive disruption, [[effect:nausea]], and cardiovascular [[effect:stimulation]], compressed into a 20–60-minute window with onset in 1–5 minutes{{cite|name=iceers-yopo|type=web|author=ICEERS|year=2023|title=Yopo: Basic Info|anchor=dad699d1}}. The experience varies substantially by preparation — traditional alkaline snuff, vaporized free-base bufotenine, and [[glossary:monoamine-oxidase]]-[[glossary:inhibitor]] admixtures each produce pharmacologically distinct states. Nausea and [[effect:vomiting]] are near-universal at psychoactive doses{{cite|doi=10.2174/1570159x13666141210222409|anchor=0932a7e3}}. No [[glossary:physical-dependence]] has been documented; rapid 5-HT₂A [[glossary:downregulation]] makes [[glossary:dose-escalation]] self-limiting{{cite|doi=10.1021/acschemneuro.2c00170|anchor=fc5b4139}}. The primary [[glossary:acute-risk]] is cardiovascular — [[glossary:tachycardia]], [[glossary:hypertension]], and [[effect:vasoconstriction]] are prominent at psychoactive doses, and co-administration with MAO inhibitors increases alkaloid exposure up to 9.9-fold{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=9123a299}}. No controlled human pharmacokinetic studies, dose-response studies, or clinical trials have been published for any ''A. peregrina'' preparation.

'''Yopo''' (''Anadenanthera peregrina'', Fabaceae) — cohoba, paricá — is a neotropical tree with one of the highest natural concentrations of bufotenine, a [[substance_class:chemical/tryptamine]] alkaloid. Bufotenine is a classical serotonergic [[substance_class:psychoactive/psychedelic]], chemically related to [[substance:psilocin]] and [[substance:dmt]]{{cite|doi=10.1016/j.ejmech.2024.117049|anchor=00edb406}}. It activates [[glossary:serotonin]] [[glossary:receptor|receptors]] in the [[glossary:cortex]], generating intense [[glossary:hallucination|hallucinations]] and cognitive [[glossary:disruption]] within minutes. Yopo snuff was first documented in 1496, when Friar Ramón Pané recorded the Taíno of Hispaniola inhaling it during healing and divination ceremonies{{cite|name=pane-1496|type=book|author=Pane R|year=1496|title=Relación acerca de las antigüedades de los indios|anchor=c8be260c}}. Archaeological evidence confirms ritual use across the Caribbean and Orinoco basin dating back roughly 1,000 years{{cite|doi=10.1073/pnas.1902174116|anchor=a5f7a529}}. Today the seeds are not internationally scheduled, but their alkaloids are [[glossary:schedule-i]] in the United States and controlled in most Western countries. [[index:effects|Subjective effects]] include intense geometric visuals, [[effect:ego-dissolution]], [[glossary:disorientation]], a racing heart, and [[effect:nausea]]. The experience unfolds within one to five minutes and resolves within an hour — short and self-contained, but often overwhelming{{cite|name=iceers-yopo|type=web|author=ICEERS|year=2023|title=Yopo: Basic Info|anchor=0903fcff}}. Nausea and [[effect:vomiting]] are near-universal at psychoactive doses{{cite|doi=10.2174/1570159x13666141210222409|anchor=0627db2e}} — not incidental [[glossary:adverse-effects|side effects]], but a consistent part of the experience. Yopo does not produce [[glossary:physical-dependence]]; rapid serotonin receptor adaptation makes repeated dosing self-limiting{{cite|doi=10.1021/acschemneuro.2c00170|anchor=bff67731}}. The primary [[glossary:acute-risk]] is cardiovascular — [[glossary:tachycardia]] and [[glossary:blood-pressure]] spikes are prominent at psychoactive doses — and combining yopo with [[substance_class:pharmacological/monoamine-oxidase-inhibitor|monoamine oxidase inhibitors]] multiplies alkaloid exposure up to 9.9-fold{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=71f9f58a}}, creating serious risk of a life-threatening serotonergic reaction. No controlled human trials have been published for any yopo preparation.

'''Anadenanthera peregrina''' ('''yopo''', '''cohoba''') is a Fabaceae-family tree native to the Caribbean and northern South America whose seeds contain the highest natural concentration of bufotenine among documented plant sources. The primary preparation — an alkaline snuff [[glossary:insufflation|insufflated]] nasally — produces intense serotonergic [[substance_class:psychoactive/psychedelic]] effects lasting 20–60 minutes, with a [[glossary:rapid-onset]] of 1–5 minutes{{cite|name=iceers-yopo|type=web|author=ICEERS|year=2023|title=Yopo: Basic Info|anchor=c88354d0}}. 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{{cite|name=pane-1496|type=book|author=Pane R|year=1496|title=Relación acerca de las antigüedades de los indios|anchor=f1373524}} and archaeological chemical evidence dating to approximately 1,000 CE{{cite|doi=10.1073/pnas.1902174116|anchor=ed996ab1}}. The foundational alkaloid quantification study was published by Schultes, Holmstedt, Lindgren, and Rivier in 1977{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=76d5dcb6}}. No clinical trials have been registered for yopo or bufotenine, and the substance remains largely outside formal pharmacological research; bufotenine is classified as [[glossary:schedule-i]] in the United States. Bufotenine acts as an [[glossary:agonist]] at [[glossary:5-ht2a]] [[glossary:receptor|receptors]], forming a stable salt bridge with residue D155 in the [[glossary:receptor-binding]] site and eliciting the [[glossary:head-twitch-response|head twitch response]] — a validated [[glossary:rodent-model|rodent]] proxy for hallucinogenic activity{{cite|doi=10.1016/j.ejmech.2024.117049|anchor=68bc9f60}}. The secondary alkaloids [[substance:dmt]] and [[substance:5-meo-dmt]] contribute additional [[glossary:5-ht1a]] and 5-HT₂A agonism; their relative concentrations vary dramatically with seed maturity, geographic origin, and storage duration{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=7bbbe609}}. The experiential profile is characterized by intense geometric visual phenomena, [[effect:nausea]] and cardiovascular [[effect:stimulation]], cognitive [[glossary:disruption]] at onset, and [[effect:ego-dissolution]] at higher doses. Effects and duration vary substantially by preparation method — traditionally prepared alkaline snuff, vaporized free-base bufotenine, and admixtures incorporating [[glossary:monoamine-oxidase]]-inhibiting plants each produce pharmacologically distinct experiences. Cardiovascular stimulation — [[glossary:tachycardia]], [[glossary:hypertension]], and [[effect:vasoconstriction|peripheral vasoconstriction]] producing facial flushing — is prominent at psychoactive doses and constitutes the primary acute medical risk{{cite|doi=10.2174/1570159x13666141210222409|anchor=92c4b9c9}}. No [[glossary:physical-dependence]] syndrome has been documented; rapid [[glossary:tolerance]] via 5-HT₂A [[glossary:downregulation]] makes dose-escalation self-limiting{{cite|doi=10.1021/acschemneuro.2c00170|anchor=4ba2bf38}}. Co-administration with MAO [[glossary:inhibitor|inhibitors]] increases systemic alkaloid exposure 3.6–9.9-fold and represents the most dangerous [[glossary:pharmacokinetic-interaction]]{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=a2c53dd3}}. No controlled human pharmacokinetic studies, dose-response studies, or clinical trials have been published for any ''A. peregrina'' preparation.

===Traditional and historical use=== ''Anadenanthera peregrina'' seeds have been used as psychoactive snuff — known as cohoba, yopo, jopo, and paricá — across the Caribbean and northern South America in one of the oldest documented ritual drug practices in the Americas. The first European account dates to 1496, when Friar Ramón Pané documented the Taíno of Hispaniola inhaling cohoba through Y-shaped tubes during healing and divination ceremonies{{cite|name=pane-1496|type=book|author=Pane R|year=1496|title=Relación acerca de las antigüedades de los indios|anchor=1c00265b}}. Archaeological residue analysis from a ritual bundle in the Lípez Altiplano, Bolivia (approximately 1,000 CE) identified bufotenine and [[substance:dmt]] alongside [[substance:harmine]] and [[substance:cocaine]], providing the oldest biochemically confirmed evidence of combined ''Anadenanthera'' and [[substance:ayahuasca]]-like admixture use{{cite|doi=10.1073/pnas.1902174116|anchor=d0583991}}. Traditional preparation involves toasting seeds over low heat, grinding them to fine powder, and mixing with alkaline material — calcium carbonate from shells or plant ash — then [[glossary:insufflation|insufflating]] through tubes{{cite|pubmed=12422937|anchor=57c6e4c6}}{{cite|name=iceers-yopo|type=web|author=ICEERS|year=2023|title=Yopo: Basic Info|anchor=1644bfa5}}. ===Western discovery and research=== Richard Spruce collected ''A. peregrina'' seeds at Rio Negro in 1854; these specimens were analyzed roughly 120 years later as part of the foundational alkaloid quantification study{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=97de35e4}}. Holmstedt and Lindgren first detected [[substance:5-meo-dmt]] and DMT in the seeds in 1967{{cite|name=holmstedt-lindgren-1967|type=book|author=Holmstedt B, Lindgren JE|year=1967|title=Alkaloids of Banisteriopsis and Piptadenia|anchor=fbc18df1}}. The 1977 monograph by Schultes, Holmstedt, Lindgren, and Rivier remains the definitive alkaloid quantification reference, reporting bufotenine concentrations up to 7.5% in Venezuelan seeds{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=4637d6d6}}. Torres and Repke consolidated the archaeological, ethnobotanical, and alkaloid chemistry of the genus in ''Anadenanthera: Visionary Plant of Ancient South America'' (2006){{cite|name=torres-repke-2006|type=book|author=Torres CM, Repke DB|year=2006|title=Anadenanthera: Visionary Plant of Ancient South America|anchor=0ed1018a}}. ===Modern era=== DMT was listed as [[glossary:schedule-i]] under the UN [[glossary:convention-on-psychotropic-substances]] in 1971; bufotenine and 5-MeO-DMT were not internationally scheduled{{cite|name=un-convention-1971|type=legal|author=UNODC|year=1971|title=Convention on Psychotropic Substances 1971|anchor=9767d02f}}. In the United States, bufotenine was placed on Schedule I ([[glossary:drug-enforcement-administration|DEA]] code 7433). In the United Kingdom, bufotenine and DMT were classified as [[glossary:class-a]] under the Misuse of Drugs Act 1971. No clinical trials for ''A. peregrina'', yopo, or bufotenine have been registered. {{DiscoverMore|Indigenous and traditional use}} Ethnographic records document diverse use traditions across the Orinoco basin. Yanomami shamans in Venezuela and Brazil inhale ''yakoana'' snuff to summon ''xapiripë'' spirits for healing and communal protection{{flag|citation-needed}}. Among the Piaroa, shamans add ''Banisteriopsis caapi'' cuttings to the preparation and consume ''B. caapi'' prior to insufflation to modulate vision [[glossary:intensity]]; yopo holds a central position in cosmological narratives and shamanic identity{{cite|pubmed=12422937|anchor=9643a7f5}}. Among the Cuiva of Colombia and Venezuela, yopo use has been linked to cultural resistance and assertion of indigenous identity{{cite|doi=10.1080/02791072.2011.566499|anchor=722c4baa}}. {{/DiscoverMore}}

====Discovery and early record==== ''Anadenanthera peregrina'' was originally described by Carl Linnaeus as ''Mimosa peregrina'' in ''Species Plantarum'' (1753). The species was subsequently transferred through several genera — to ''Acacia'' by Willdenow, to ''Piptadenia'' by Bentham — before Carlos Luis Spegazzini established the current binomial in 1923{{cite|name=powo-anadenanthera|type=database|author=Royal Botanic Gardens Kew|year=2024|title=Anadenanthera peregrina — Plants of the World Online|anchor=8d023ca6}}. ====Traditional use==== The use of ''A. peregrina'' seeds as psychoactive snuff — known variously as cohoba, yopo, jopo, and paricá — represents one of the oldest documented ritual drug practices in the Americas. The first European account dates to 1496, when Friar Ramón Pané, commissioned by Christopher Columbus, documented the Taíno of Hispaniola inhaling cohoba snuff through Y-shaped tubes during healing and divination rituals{{cite|name=pane-1496|type=book|author=Pane R|year=1496|title=Relación acerca de las antigüedades de los indios|anchor=b75d3bd1}}. Archaeological residue analysis from a ritual bundle in the Lípez Altiplano, Bolivia (approximately 1,000 CE) identified bufotenine and [[substance:dmt]] alongside [[substance:harmine]] and [[substance:cocaine]] in snuffing paraphernalia, providing the oldest biochemically confirmed evidence of combined ''Anadenanthera'' and [[substance:ayahuasca]]-like admixture use{{cite|doi=10.1073/pnas.1902174116|anchor=1704b355}}. Ethnographic documentation records diverse use traditions across the Orinoco basin. Yanomami shamans in Venezuela and Brazil inhale ''yakoana'' (yopo) snuff to summon ''xapiripë'' spirits for healing and communal protection{{flag|citation-needed}}. 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 [[glossary:intensity]]; yopo occupies a central position in cosmological narratives and shamanic identity{{cite|pubmed=12422937|anchor=6f2541f0}}. 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{{cite|doi=10.1080/02791072.2011.566499|anchor=f587ea94}}. Traditional preparation involves toasting seeds over low heat, grinding to fine powder, and mixing with alkaline material — calcium carbonate from shells or plant ash. The resulting powder is blown through a long tube into the recipient's nostrils by an assistant, or self-administered with a Y-shaped tube{{cite|pubmed=12422937|anchor=ef874efa}}{{cite|name=iceers-yopo|type=web|author=ICEERS|year=2023|title=Yopo: Basic Info|anchor=dcb369a6}}. ====Western scientific history==== Richard Spruce collected ''A. peregrina'' seeds at Rio Negro in 1854; these specimens were analyzed approximately 120 years later as part of the foundational alkaloid quantification study{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=673cc545}}. Holmstedt and Lindgren first detected [[substance:5-meo-dmt]] and DMT in the seeds in 1967{{cite|name=holmstedt-lindgren-1967|type=book|author=Holmstedt B, Lindgren JE|year=1967|title=Alkaloids of Banisteriopsis and Piptadenia|anchor=52f7aabe}}. The 1977 monograph by Schultes, Holmstedt, Lindgren, and Rivier remains the definitive alkaloid quantification study, reporting bufotenine concentrations up to 7.5% in Venezuelan seeds{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=c5a95d6b}}. Torres and Repke published ''Anadenanthera: Visionary Plant of Ancient South America'' in 2006, consolidating the archaeological, ethnobotanical, and alkaloid chemistry of the genus into a single reference monograph{{cite|name=torres-repke-2006|type=book|author=Torres CM, Repke DB|year=2006|title=Anadenanthera: Visionary Plant of Ancient South America|anchor=4f7cb3a7}}. ====Regulatory history==== DMT was listed as [[glossary:schedule-i]] under the UN [[glossary:convention-on-psychotropic-substances]] in 1971; bufotenine and 5-MeO-DMT were not listed, and plants containing scheduled substances are explicitly not subject to [[glossary:international-control]] under this treaty{{cite|name=un-convention-1971|type=legal|author=UNODC|year=1971|title=Convention on Psychotropic Substances 1971|anchor=6a62bf00}}. In the United States, bufotenine was placed on Schedule I of the [[glossary:controlled-substances-act]] ([[glossary:drug-enforcement-administration|DEA]] code 7433). In the United Kingdom, bufotenine and DMT were classified as [[glossary:class-a]] drugs under the Misuse of Drugs Act 1971. No clinical trials for ''A. peregrina'', yopo, or bufotenine have been registered on [[glossary:clinicaltrials-gov]].

===Traditional and historical use=== ''Anadenanthera peregrina'' seeds have been used as psychoactive snuff — cohoba, yopo, jopo, or paricá — across the Caribbean and northern South America for well over a thousand years. The first European account dates to 1496, when Friar Ramón Pané documented the Taíno of Hispaniola inhaling cohoba through Y-shaped tubes during healing and divination ceremonies{{cite|name=pane-1496|type=book|author=Pane R|year=1496|title=Relación acerca de las antigüedades de los indios|anchor=76c1bf20}}. A ritual bundle from Bolivia dated to around 1,000 CE contained bufotenine, [[substance:dmt]], and [[substance:harmine]] together — the oldest biochemical confirmation of combined yopo and [[substance:ayahuasca]]-like use in the Americas{{cite|doi=10.1073/pnas.1902174116|anchor=57ee42aa}}. ===Western discovery and research=== Western scientific interest began when Richard Spruce collected seeds at Rio Negro in 1854; Holmstedt and Lindgren first identified [[substance:5-meo-dmt]] and DMT in the seeds in 1967{{cite|name=holmstedt-lindgren-1967|type=book|author=Holmstedt B, Lindgren JE|year=1967|title=Alkaloids of Banisteriopsis and Piptadenia|anchor=27c803cf}}, and the definitive 1977 Schultes monograph documented bufotenine concentrations up to 7.5% of dry seed weight{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=5e424fca}}. Traditional preparation — toasting seeds, grinding to powder, mixing with alkaline ash, and [[glossary:insufflation|insufflating]] — remained unchanged across these centuries{{cite|pubmed=12422937|anchor=2141d38d}}{{cite|name=iceers-yopo|type=web|author=ICEERS|year=2023|title=Yopo: Basic Info|anchor=ab9ec82a}}. Torres and Repke's 2006 ethnobotanical [[glossary:synthesis]] consolidated the archaeological and chemical record{{cite|name=torres-repke-2006|type=book|author=Torres CM, Repke DB|year=2006|title=Anadenanthera: Visionary Plant of Ancient South America|anchor=c00473b2}}. ===Modern era=== DMT was listed as [[glossary:schedule-i]] under the UN [[glossary:convention-on-psychotropic-substances]] in 1971; bufotenine and 5-MeO-DMT were not internationally listed{{cite|name=un-convention-1971|type=legal|author=UNODC|year=1971|title=Convention on Psychotropic Substances 1971|anchor=20a0aac3}}. In the United States, bufotenine was separately placed on Schedule I ([[glossary:drug-enforcement-administration|DEA]] code 7433); in the United Kingdom, bufotenine and DMT became [[glossary:class-a]] under the Misuse of Drugs Act 1971. No clinical trials for yopo or bufotenine have been registered. {{DiscoverMore|Indigenous and traditional use}} Ethnographic records document diverse use traditions across the Orinoco basin. Yanomami shamans in Venezuela and Brazil inhale ''yakoana'' snuff to summon ''xapiripë'' spirits for healing and communal protection{{flag|citation-needed}}. Among the Piaroa, shamans add ''Banisteriopsis caapi'' cuttings to the preparation and consume ''B. caapi'' prior to insufflation to modulate vision [[glossary:intensity]]{{cite|pubmed=12422937|anchor=119faa6d}}. Among the Cuiva of Colombia and Venezuela, yopo use has been linked to cultural resistance and assertion of indigenous identity{{cite|doi=10.1080/02791072.2011.566499|anchor=3c0a070b}}. {{/DiscoverMore}}

'''Anadenanthera peregrina''' belongs to the family Fabaceae — the legume family. Linnaeus first described it as ''Mimosa peregrina'' in 1753; it passed through ''Acacia'' and ''Piptadenia'' before Spegazzini established the current binomial in 1923{{cite|name=powo-anadenanthera|type=database|author=Royal Botanic Gardens Kew|year=2024|title=Anadenanthera peregrina — Plants of the World Online|anchor=b5fc29e4}}. A closely related species, ''Anadenanthera colubrina'' (cebil, vilca), shares similar alkaloid chemistry and traditional use across southern South America. The tree is native to the Caribbean islands, the Orinoco basin, and the tropical savannas and dry forests of northern South America — from Colombia and Venezuela through Brazil. It grows in open woodland and disturbed forest margins from sea level to roughly 1,000 meters. It is not commercially cultivated but persists in wild and semi-managed populations across its native range. ''A. peregrina'' reaches 15–25 meters in height, with dark, rough bark often covered in conical spines. Leaves are finely compound, resembling those of other mimosoid legumes. The tree produces small spherical clusters of white or pale yellow flowers and flat, dark brown seed pods containing 3–10 glossy, lens-shaped seeds about 1–2 cm across — the only plant part used for psychoactive preparation. Bark, leaves, and roots do not contain psychoactive concentrations of the relevant alkaloids.

The genus ''Anadenanthera'' has historically been treated as containing two species — ''A. peregrina'' and ''A. colubrina'' (Vell.) Brenan{{cite|doi=10.7717/peerj.10579|anchor=befd2794}}. A 2024 molecular genetics study supports a four-species [[glossary:hypothesis]], treating the cerrado taxon (''A. peregrina'' var. ''falcata'') as a distinct species; this reclassification is not yet universally adopted{{flag|citation-needed}}. 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{{cite|pubmed=24077673|anchor=7e69d4b8}}. The basionym ''Mimosa peregrina'' L. has passed through thirteen synonyms, including ''Acacia peregrina'' (L.) Willd., ''Piptadenia peregrina'' (L.) Benth., ''Acacia niopo'' (Humb. & Bonpl. ex Willd.) Kunth, and ''Niopa peregrina'' (L.) Britton & Rose{{cite|name=powo-anadenanthera|type=database|author=Royal Botanic Gardens Kew|year=2024|title=Anadenanthera peregrina — Plants of the World Online|anchor=aabb0c0d}}. ''A. peregrina'' is a deciduous to semi-deciduous tree, typically 5–20 m tall, with bipinnate leaves bearing numerous small leaflets, spherical white flower heads, flat spirally twisted seed pods, and dark brown to black lenticular seeds. The bark contains high condensed tannin content (587 mg catechin equivalents per gram extract) alongside gallic acid, catechin, epicatechin, flavonoids, saponins, phenols, and coumarins{{cite|doi=10.1371/journal.pone.0189263|anchor=876dbb16}}{{cite|doi=10.1590/1519-6984.234476|anchor=471b34fb}}. These bark constituents are distinct from the seed alkaloid profile and are not relevant to psychoactive effects. The native range spans Bolivia, Brazil (North, Northeast, and Southeast regions), Colombia, Dominican Republic, French Guiana, Guyana, Haiti, Leeward Islands, Puerto Rico, Suriname, Trinidad-Tobago, Venezuela, and Windward Islands, with introduction to St. Helena{{cite|name=powo-anadenanthera|type=database|author=Royal Botanic Gardens Kew|year=2024|title=Anadenanthera peregrina — Plants of the World Online|anchor=72530961}}. The species inhabits seasonally dry tropical biomes, gallery forests, and savanna edges{{cite|pubmed=24077673|anchor=f26adc6e}}. No formal cultivar development has been documented. Seeds are sold commercially in Europe and North America via online retailers without standardized alkaloid content or quality controls. ====Misidentification risk==== ''A. colubrina'' (cebil, vilca) is morphologically similar, and bark anatomy differences between the two species are insufficient for reliable taxonomic identification{{cite|doi=10.1371/journal.pone.0189263|anchor=0e5119ac}}. The two species share similar alkaloid profiles but differ in geographic range: ''A. colubrina'' predominates in the Andes and southern South America, while ''A. peregrina'' occupies the Orinoco basin, Amazon, and Caribbean. No other look-alike species with distinct [[glossary:toxicity|toxicity profiles]] have been documented.

''Anadenanthera peregrina'' belongs to the family Fabaceae (legume family). Originally described by Linnaeus as ''Mimosa peregrina'' in ''Species Plantarum'' (1753), the species was transferred through ''Acacia'' and ''Piptadenia'' before Spegazzini established the current binomial in 1923{{cite|name=powo-anadenanthera|type=database|author=Royal Botanic Gardens Kew|year=2024|title=Anadenanthera peregrina — Plants of the World Online|anchor=000ee498}}. A closely related species, ''Anadenanthera colubrina'' (cebil, vilca), shares similar alkaloid chemistry and traditional use patterns in southern South America. The tree is native to the Caribbean islands, the Orinoco basin, and the tropical savannas and dry forests of northern South America, from Colombia and Venezuela through Brazil. It grows in open woodland, cerrado, and disturbed forest margins at [[glossary:elevation|elevations]] from sea level to approximately 1,000 meters. ''A. peregrina'' is not cultivated commercially but persists in wild and semi-managed populations across its native range. ''A. peregrina'' is a medium to large deciduous tree reaching 15–25 meters in height, with dark, rough bark often covered in conical spines. Leaves are bipinnately compound with numerous small leaflets, resembling those of other mimosoid legumes. The tree produces spherical clusters of white or pale yellow flowers and flat, dark brown seed pods containing 3–10 glossy, lens-shaped seeds approximately 1–2 cm in diameter. Seeds are harvested when mature pods darken and split open. The seeds are the only plant part used for psychoactive preparation — bark, leaves, and roots do not contain psychoactive concentrations of the relevant [[substance_class:chemical/tryptamine|tryptamines]]. Detailed preparation methods are described in the Preparations section.

bufotenine (5-hydroxy-''N'',''N''-dimethyltryptamine) is the dominant psychoactive alkaloid in ''A. peregrina'' seeds, present at the highest natural concentration of any documented plant source. The definitive quantification study reported bufotenine at up to 7.5% of seed dry weight in Venezuelan specimens{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=7c374acf}}. Bufotenine acts as a [[glossary:5-ht2a]] [[glossary:agonist|receptor agonist]], producing classical [[substance_class:psychoactive/psychedelic]] effects through the same serotonergic pathway as psilocybin and [[substance:dmt]]{{cite|doi=10.1016/j.ejmech.2024.117049|anchor=228e57b3}}. The seeds contain two secondary [[substance_class:chemical/tryptamine]] alkaloids — DMT (''N'',''N''-dimethyltryptamine) and [[substance:5-meo-dmt]] (5-methoxy-''N'',''N''-dimethyltryptamine) — that contribute additional psychoactive effects. 5-MeO-DMT has primary [[glossary:affinity]] for [[glossary:5-ht1a]] [[glossary:receptor|receptors]]{{cite|doi=10.1038/s41586-024-07403-2|anchor=023277a8}}, adding an [[substance_class:psychoactive/anxiolytic]] and [[substance_class:psychoactive/dissociative]] dimension. DMT acts across 5-HT₁A, 5-HT₂A, [[glossary:5-ht2c]], [[glossary:sigma-1-receptor]], and [[glossary:taar1]] [[glossary:receptor-system|receptor systems]]{{cite|doi=10.1007/s00213-022-06065-0|anchor=734c1d1f}}. All three alkaloids converge downstream on the Gq/phosphoinositide [[glossary:hydrolysis]] cascade that mediates psychedelic effects{{cite|doi=10.1124/pharmrev.120.000056|anchor=35777ec4}}. The ratio of bufotenine to DMT to 5-MeO-DMT varies dramatically with seed maturity, geographic origin, and storage duration{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=5e51fae4}}. Seeds from different provenances produce pharmacologically distinct preparations — a batch dominated by bufotenine will produce a different experience from one with a higher proportion of 5-MeO-DMT. No commercial standardization or alkaloid content testing exists for seeds sold online. [[glossary:cyp2d6]] catalyzes the O-demethylation of 5-MeO-DMT to bufotenine ''in vivo'', a metabolic conversion significantly affected by [[glossary:genetic-polymorphism]]: [[glossary:poor-metabolizer|poor metabolizers]] show 2.6–40-fold lower catalytic efficiency{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=b01b3c5e}}. [[glossary:mao-a]] is the primary [[glossary:degradation]] pathway for all three alkaloids{{cite|pubmed=20942780|anchor=2633a038}}.

====Dominant alkaloid: bufotenine==== Bufotenine (5-hydroxy-''N'',''N''-dimethyltryptamine; C₁₂H₁₆N₂O; MW 204.27) is the dominant alkaloid in mature ''A. peregrina'' seeds. Schultes, Holmstedt, Lindgren, and Rivier reported concentrations of 7.5% in southern Venezuelan seeds, with bufotenine constituting approximately 80% of total alkaloid content in mature Puerto Rico specimens (March 1975 collection){{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=1ca24860}}. Brazilian seeds yielded 1.1% bufotenine in earlier analyses. After two years of storage, Puerto Rico seeds retained 3.5% bufotenine as their sole detectable alkaloid, demonstrating bufotenine's chemical [[glossary:stability]]{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=17cfec3f}}. Average values per gram of seed have been reported as approximately 74 mg bufotenine, 1.6 mg [[substance:dmt]], and 0.4 mg [[substance:5-meo-dmt]]{{cite|name=iceers-yopo|type=web|author=ICEERS|year=2023|title=Yopo: Basic Info|anchor=c475b0e4}}. ====Secondary alkaloids: DMT and 5-MeO-DMT==== DMT (''N'',''N''-dimethyltryptamine; C₁₂H₁₆N₂; MW 188.27) was first detected in ''A. peregrina'' seeds by Holmstedt and Lindgren in 1967{{cite|name=holmstedt-lindgren-1967|type=book|author=Holmstedt B, Lindgren JE|year=1967|title=Alkaloids of Banisteriopsis and Piptadenia|anchor=b1223c35}}. In immature Puerto Rico seeds (December 1972 collection), DMT constituted 0.16% of seed weight and 75% of total alkaloid content — demonstrating that immature seeds are DMT-dominant, in sharp contrast to the bufotenine dominance of mature seeds{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=77404a52}}. In mature Puerto Rico seeds (March 1975), DMT had dropped to 19% of total alkaloid. DMT is less chemically stable than bufotenine and degrades during seed maturation and storage; in the 120-year-old Spruce collection specimen, DMT was entirely absent{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=0fdea76f}}{{cite|name=erowid-anadenanthera|type=web|author=Keeper of the Trout|year=2001|title=Anadenanthera peregrina Alkaloid Data|anchor=8405544a}}. 5-MeO-DMT (5-methoxy-''N'',''N''-dimethyltryptamine; C₁₃H₁₈N₂O; MW 218.29) was first detected in seeds from the Rio Branco region of Brazil (1953 specimens){{cite|name=holmstedt-lindgren-1967|type=book|author=Holmstedt B, Lindgren JE|year=1967|title=Alkaloids of Banisteriopsis and Piptadenia|anchor=a4137d3f}}. Maximum reported concentration is 0.04% in immature seeds, constituting approximately 1% of total alkaloid in fresh mature material. 5-MeO-DMT degrades rapidly in storage and is not detected in seeds aged beyond two years{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=627d9869}}{{cite|name=erowid-anadenanthera|type=web|author=Keeper of the Trout|year=2001|title=Anadenanthera peregrina Alkaloid Data|anchor=0f69feb6}}. ====Minor constituents==== DMT-''N''-oxide and bufotenine-''N''-oxide have been detected in some snuff preparations{{cite|name=erowid-anadenanthera|type=web|author=Keeper of the Trout|year=2001|title=Anadenanthera peregrina Alkaloid Data|anchor=8703a513}}. Trace amounts of 2-methyl-1,2,3,4-tetrahydro-β-carboline were detected in 1975 Puerto Rico seeds{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=bec4d47e}}. No β-carboline [[substance_class:pharmacological/monoamine-oxidase-inhibitor|monoamine oxidase inhibitors]] have been detected in the seeds themselves, in contrast to ''Banisteriopsis caapi''. This distinction is pharmacologically significant: the seeds alone do not provide [[glossary:monoamine-oxidase|MAO]] [[glossary:inhibition]], and oral bioactivity of the [[substance_class:chemical/tryptamine]] alkaloids would require exogenous MAO [[glossary:inhibitor]] co-administration. ====Variability==== Alkaloid concentration profiles vary substantially across three axes: geographic origin (Venezuelan seeds consistently show the highest bufotenine concentrations), seed maturity (immature seeds are DMT- and 5-MeO-DMT-rich; mature seeds are bufotenine-dominant), and storage duration (DMT and 5-MeO-DMT degrade within months to years; bufotenine remains stable for decades){{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=e4815d3d}}{{cite|name=erowid-anadenanthera|type=web|author=Keeper of the Trout|year=2001|title=Anadenanthera peregrina Alkaloid Data|anchor=ff281f45}}. Commercial seeds sold without maturity or provenance information may vary widely in alkaloid composition, and no standardized analytical testing program exists for this market. ====Preparation effects on constituent ratios==== Addition of alkaline ash (lime or plant ash) during traditional preparation converts alkaloid salts to free-base form, dramatically improving nasal mucosal [[glossary:absorption]] of all three alkaloids{{cite|name=iceers-yopo|type=web|author=ICEERS|year=2023|title=Yopo: Basic Info|anchor=6765ca55}}. Heat during seed roasting may cause partial [[glossary:degradation]] of DMT and 5-MeO-DMT relative to the more thermostable bufotenine; specific degradation data are not published. Admixture with ''Banisteriopsis caapi'' introduces [[substance:harmaline]] and [[substance:harmine]] (reversible [[glossary:mao-a]] inhibitors), which inhibit enzymatic degradation of all three alkaloids and substantially increase [[glossary:systemic-exposure]]; [[glossary:cyp2d6]]-mediated O-demethylation of 5-MeO-DMT to bufotenine is also modulated by harmaline at higher doses{{cite|doi=10.1124/dmd.112.050724|anchor=c7f3d2e4}}{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=f65223bb}}.

Bufotenine (5-hydroxy-''N'',''N''-dimethyltryptamine) is the dominant psychoactive alkaloid in ''A. peregrina'' seeds, present at the highest natural concentration of any documented plant source — up to 7.5% of seed dry weight in Venezuelan specimens{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=d766a13a}}. It acts on [[glossary:serotonin]] [[glossary:receptor|receptors]] through the same pathway as psilocybin and [[substance:dmt]]{{cite|doi=10.1016/j.ejmech.2024.117049|anchor=f157038f}}, producing the intense visual and cognitive [[glossary:disruption]] characteristic of the yopo experience. The seeds also contain two secondary [[substance_class:chemical/tryptamine|tryptamines]]: DMT (''N'',''N''-dimethyltryptamine) and [[substance:5-meo-dmt]] (5-methoxy-''N'',''N''-dimethyltryptamine). 5-MeO-DMT acts on a different serotonin pathway from bufotenine, adding an [[substance_class:psychoactive/anxiolytic]] and [[substance_class:psychoactive/dissociative]] dimension to the experience{{cite|doi=10.1038/s41586-024-07403-2|anchor=4734a91c}}. DMT engages multiple serotonin and other [[glossary:receptor-system|receptor systems]] simultaneously{{cite|doi=10.1007/s00213-022-06065-0|anchor=1cdd7c29}}. All three alkaloids converge downstream on the same cellular [[glossary:signaling-cascade]] that mediates [[substance_class:psychoactive/psychedelic]] effects{{cite|doi=10.1124/pharmrev.120.000056|anchor=ff5d89be}}. The ratio of bufotenine to DMT to 5-MeO-DMT varies substantially with seed maturity, geographic origin, and storage duration{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=dd966df1}}. A batch dominated by bufotenine produces a different experience from one with more 5-MeO-DMT. [[glossary:cyp2d6]], a liver [[glossary:enzyme]], converts 5-MeO-DMT into bufotenine in the body — individuals with slow-metabolizer genetics show dramatically lower conversion rates{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=bdf59fae}}. [[glossary:mao-a]] is the primary enzyme that clears all three alkaloids{{cite|pubmed=20942780|anchor=a73e44de}}.

===Where it acts=== Bufotenine binds the [[glossary:5-ht2a]] [[glossary:receptor]] through a hydrogen bond with residue L229 and a stable salt bridge with residue D155{{cite|doi=10.1016/j.ejmech.2024.117049|anchor=66935a81}}. It also activates [[glossary:5-ht2c]]{{cite|pubmed=8700116|anchor=a085ddea}}. The secondary alkaloids extend the pharmacological reach: [[substance:5-meo-dmt]] acts primarily at [[glossary:5-ht1a]]{{cite|doi=10.1038/s41586-024-07403-2|anchor=2d67c239}}, while [[substance:dmt]] engages 5-HT₁A, 5-HT₂A, 5-HT₂C, [[glossary:sigma-1-receptor]], and [[glossary:taar1]]{{cite|doi=10.1007/s00213-022-06065-0|anchor=273296ae}}. ===What it changes=== Early researchers questioned whether bufotenine crossed the [[glossary:blood-brain-barrier]], attributing its effects to peripheral cardiovascular actions. This has been resolved: chronic administration in mice demonstrated bufotenine [[glossary:accumulation]] in brain tissue{{cite|doi=10.1155/2018/1032638|anchor=dd63bde9}}, and 5-HT₂A binding with head twitch confirmation establishes central [[substance_class:psychoactive/psychedelic]] activity{{cite|doi=10.1016/j.ejmech.2024.117049|anchor=2d40187f}}. Microiontophoretic studies show bufotenine antagonizes [[glossary:serotonin]] excitatory effects on [[glossary:brainstem]] [[glossary:neuron|neurons]] — a mechanism of [[glossary:psychotomimetic]] action shared with [[substance:lsd]]{{cite|doi=10.1111/j.1476-5381.1974.tb09609.x|anchor=9112b7a3}}. [[substance_class:pharmacological/monoamine-oxidase-inhibitor]] co-administration dramatically reshapes the pharmacokinetic profile: [[substance:harmaline]] increases systemic 5-MeO-DMT exposure 3.6–4.4-fold and bufotenine exposure 9.9-fold{{cite|doi=10.1124/dmd.112.050724|anchor=c413bf7d}}, providing the pharmacokinetic basis for the traditional Piaroa practice of combining yopo with ''B. caapi''{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=84525204}}. {{DiscoverMore|Open Questions}} * No human pharmacokinetic studies have been published — T''max'', C''max'', and [[glossary:half-life]] for bufotenine remain unknown via any route. * The relative contribution of each alkaloid to the [[glossary:subjective-experience]] is uncharacterized; no studies have administered isolated bufotenine, DMT, and 5-MeO-DMT at yopo-equivalent ratios. * No neuroimaging studies (fMRI, PET, EEG) have been conducted with ''A. peregrina'' or yopo snuff. {{/DiscoverMore}}

===Where it acts=== Bufotenine activates [[glossary:5-ht2a]] and [[glossary:5-ht2c]] [[glossary:serotonin]] [[glossary:receptor|receptors]] in the brain's [[glossary:cortex]] — the same primary targets as psilocybin and [[substance:lsd]]{{cite|doi=10.1016/j.ejmech.2024.117049|anchor=65d62e6f}}{{cite|pubmed=8700116|anchor=d7dd278b}}. Early researchers doubted bufotenine could even reach the brain; [[glossary:animal-model|animal studies]] settled this, showing it accumulates in brain tissue and produces central [[substance_class:psychoactive/psychedelic]] effects{{cite|doi=10.1155/2018/1032638|anchor=b56b85d7}}. The secondary alkaloids extend the pharmacological reach — [[substance:5-meo-dmt]] acts on a different serotonin pathway{{cite|doi=10.1038/s41586-024-07403-2|anchor=b10c5747}}, and [[substance:dmt]] activates multiple [[substance_class:pharmacological/serotonin-system|serotonin systems]] simultaneously{{cite|doi=10.1007/s00213-022-06065-0|anchor=4d7d45c9}}. ===What it changes=== Bufotenine dampens serotonin's excitatory effects on [[glossary:brainstem]] [[glossary:neuron|neurons]] — a mechanism shared with LSD{{cite|doi=10.1111/j.1476-5381.1974.tb09609.x|anchor=7c9702b5}}. [[glossary:mao-a]] breaks down all three seed alkaloids; blocking that [[glossary:enzyme]] — whether with pharmaceutical MAOIs or with ''Banisteriopsis caapi'', which contains [[substance:harmine]] and [[substance:harmaline]] — raises bufotenine exposure up to 9.9-fold{{cite|doi=10.1124/dmd.112.050724|anchor=a6c87454}}{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=ebe96d47}}. {{DiscoverMore|Open Questions}} * No human pharmacokinetic studies have been published — T''max'', C''max'', and [[glossary:half-life]] for bufotenine remain unknown via any route. * The relative contribution of each alkaloid to the [[glossary:subjective-experience]] is uncharacterized; no studies have administered isolated bufotenine, DMT, and 5-MeO-DMT at yopo-equivalent ratios. * No neuroimaging studies (fMRI, PET, EEG) have been conducted with ''A. peregrina'' or yopo snuff. {{/DiscoverMore}}

The yopo experience is defined by its compressed arc and somatic weight. The experience arrives within minutes and ends within an hour, but onset is often overwhelming — [[effect:nausea]] and a racing heart begin before the visual phase even [[glossary:peak|peaks]]. Geometric [[glossary:hallucination|hallucinations]], [[effect:ego-dissolution]], and intense cognitive [[glossary:disruption]] unfold while the body is already under significant physical strain. Traditional ritual context consistently shapes psychological outcomes and is reported to substantially reduce panic and [[glossary:disorientation]]. Pharmacologically, yopo sits between vaporized [[substance:dmt]] and oral [[substance:ayahuasca]]. It shares the [[glossary:rapid-onset]] and short duration of smoked DMT, but the dominant bufotenine action and prominent peripheral serotonergic effects give it a heavier somatic character. Preparation method is the primary modifier: alkaline snuff, vaporized free-base bufotenine, and [[glossary:monoamine-oxidase]]-[[glossary:inhibitor]] admixtures produce pharmacologically distinct states — differing in [[glossary:intensity]], duration, and the balance between visual depth and body-load.

====Yopo snuff (nasal insufflation)==== The traditional preparation involves toasting mature ''A. peregrina'' seeds over low heat, grinding to a fine powder, and mixing with alkaline material — typically calcium carbonate from shells or plant ash{{cite|pubmed=12422937|anchor=5e3f9b0b}}{{cite|name=iceers-yopo|type=web|author=ICEERS|year=2023|title=Yopo: Basic Info|anchor=b56abf37}}. The alkaline additive converts alkaloid salts to free-base form, which is essential for efficient nasal mucosal [[glossary:absorption]]. The resulting snuff is administered by an assistant blowing the powder through a long tube into the recipient's nostrils, or self-administered with a Y-shaped tube. '''Yopo snuff (nasal insufflation):''' Threshold ~30 mg prepared snuff; light 65–300 mg; common 300–540 mg; strong 540–800 mg; heavy >800 mg. Onset 1–5 min; peak 5–20 min; total duration 20–60 min primary effects, 60–120 min including residual effects{{cite|name=iceers-yopo|type=web|author=ICEERS|year=2023|title=Yopo: Basic Info|anchor=23b33cda}}. {{Warning}}All dose values for yopo snuff derive from the ICEERS [[index:harm-reduction|harm reduction]] resource, not from peer-reviewed dose-ranging studies. No controlled human dose-response data have been published for any ''A. peregrina'' preparation. Alkaloid content varies substantially across seed batches depending on provenance, maturity, and [[glossary:storage-conditions]].{{/Warning}} [[effect:nausea]] and [[effect:vomiting]] are nearly universal at psychoactive doses. Intense cardiovascular [[effect:stimulation]] — [[glossary:tachycardia]], [[glossary:hypertension]], facial flushing — accompanies the psychoactive effects and begins within minutes of administration. See the Dose by preparation card for the full dose-tier breakdown. ====Vaporized free-base bufotenine==== Free-base bufotenine can be vaporized and inhaled. The reported [[glossary:dose-range|active dose range]] is 2–8 mg{{flag|safety-citation-needed}}, substantially lower than the nasal snuff dose range, reflecting higher [[glossary:bioavailability]] through pulmonary absorption. Onset is rapid (seconds to approximately 1 minute). Closed-eye visual phenomena — colored ring-like and swirling patterns — have been described at these doses{{flag|citation-needed}}. No published human pharmacokinetic data or controlled dose-response studies exist for this preparation. ====B. caapi admixture (Piaroa practice)==== Piaroa shamans add ''Banisteriopsis caapi'' cuttings to the yopo preparation and consume ''B. caapi'' doses prior to snuff inhalation{{cite|pubmed=12422937|anchor=2c9939ea}}. The [[substance:harmaline]] and [[substance:harmine]] content of ''B. caapi'' provides reversible [[glossary:mao-a]] [[glossary:inhibition]], which dramatically prolongs and intensifies the effects of all three seed alkaloids by inhibiting their primary metabolic inactivation pathway{{cite|doi=10.1124/dmd.112.050724|anchor=0586e536}}{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=490e777a}}. This combination produces a fundamentally different pharmacological profile compared to yopo snuff alone: duration is extended, [[glossary:intensity]] is amplified, and [[glossary:serotonin-syndrome]] risk becomes clinically significant. {{Warning}}Co-administration with [[substance_class:pharmacological/monoamine-oxidase-inhibitor|monoamine oxidase 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 risk{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=edceb5ce}}. The dose of ''B. caapi'' in this preparation is not standardized and varies by practitioner.{{/Warning}} ====Effect modifiers==== [[glossary:potency]] and effect character are modulated by seed maturity (immature seeds contain higher [[substance:dmt]] and [[substance:5-meo-dmt]] concentrations; mature seeds are predominantly bufotenine), geographic provenance, storage duration, alkaline ash quality, and the presence or absence of [[glossary:monoamine-oxidase|MAO]]-inhibiting admixtures{{cite|name=schultes-1977|type=book|author=Schultes RE, Holmstedt B, Lindgren JE, Rivier L|year=1977|title=The tryptamine alkaloids of Piptadenia peregrina|anchor=4a1c27a3}}. Traditional ritual context — including an experienced guide, structured setting, and cultural framework — is reported to reduce adverse psychological outcomes, though no controlled comparison has been published{{cite|doi=10.1080/02791072.2011.566499|anchor=ab5242d5}}{{cite|pubmed=12422937|anchor=7769a8ef}}.

The yopo experience is defined by its compressed temporal arc and somatic [[glossary:intensity]]. [[effect:nausea]], [[effect:vomiting]], and cardiovascular [[effect:stimulation]] are not incidental [[glossary:adverse-effects]] but integral to the experience — they precede and overlap with the perceptual phase, shaping its overall character. Onset is rapid and often overwhelming; geometric visuals, cognitive [[glossary:disruption]], and [[effect:ego-dissolution]] unfold within minutes, then resolve within an hour. [[glossary:set-and-setting]] [[glossary:sensitivity]] is high, and traditional ritual context is reported to substantially modulate psychological outcomes. Pharmacologically, yopo sits between vaporized [[substance:dmt]] and oral [[substance:ayahuasca]]. It shares the [[glossary:rapid-onset]] and short duration of smoked DMT, but the dominant bufotenine action, prominent peripheral serotonergic effects, and somatic weight of onset distinguish it from other [[substance_class:chemical/tryptamine]] preparations. The preparation method is the primary modifier: alkaline snuff, vaporized free-base, and [[glossary:monoamine-oxidase]]-[[glossary:inhibitor]] admixtures each produce pharmacologically distinct states.

====Toxicity==== No human [[glossary:fatality]] attributed to yopo snuff or bufotenine has been identified in peer-reviewed literature. In chronic mouse studies, [[glossary:intraperitoneal]] bufotenine at doses of 0.63, 1.05, and 2.1 mg/animal/day for 21 days produced dose-dependent mild behavioral changes with no histological organ damage; the lowest effective dose was assessed as safe{{cite|doi=10.1155/2018/1032638|anchor=0da2e67c}}. The alkaloid accumulated in heart and kidney at all doses, and in lungs and brain at higher doses{{cite|doi=10.1155/2018/1032638|anchor=807428e2}}. Cardiovascular effects are prominent and clinically significant at psychoactive doses. Historical human administration studies documented [[glossary:tachycardia]], [[glossary:hypertension]], intense [[effect:vasoconstriction|peripheral vasoconstriction]] producing facial purpling and cyanosis, chest heaviness, and increased respiratory rate{{flag|safety-citation-needed}}. [[effect:nausea]] and [[effect:vomiting]] are near-universal, mediated by peripheral serotonin₃ and 5-HT₄ [[glossary:receptor-activation]]{{cite|doi=10.2174/1570159x13666141210222409|anchor=be3a321f}}. No published analytical studies examine [[glossary:contamination|contaminant]] profiles — pesticide residues, heavy metals (lead, cadmium, arsenic, mercury), mycotoxins, or microbial load — in commercially sold ''A. peregrina'' seeds or prepared snuff. Seeds are sold online without standardized alkaloid content testing, and alkaloid concentrations vary substantially by provenance. Preparation with unverified alkaline substitutes may introduce additional contaminants. No Certificate of Analysis requirement or ISO/IEC-accredited laboratory program exists for this market. ====Psychological Risks==== The [[glossary:rapid-onset]] (1–5 minutes) and intense perceptual [[glossary:disruption]] create a high risk of acute [[effect:anxiety]] and panic, particularly for unprepared individuals outside ritual contexts. Bufotenine is [[glossary:psychotomimetic]] at psychoactive doses; the risk of acute [[glossary:psychotic-episodes]] is elevated in individuals with personal or family history of psychotic [[glossary:disorder|disorders]]{{cite|doi=10.1124/pharmrev.120.000056|anchor=74512cd3}}. [[glossary:hppd|Hallucinogen-persisting perception disorder]] (HPPD) is a documented risk of serotonergic [[substance_class:psychoactive/psychedelic]] use; yopo-specific risk has not been studied but is extrapolated from [[substance:lsd]] and psilocybin data{{cite|doi=10.1007/s00213-022-06066-z|anchor=7276c179}}. No peer-reviewed [[glossary:case-report|case reports]] of adverse psychiatric events specific to yopo snuff have been published. ====Tolerance & Dependence==== [[glossary:serotonergic-psychedelics|Classical serotonergic psychedelics]] produce rapid [[glossary:tolerance]] via [[glossary:5-ht2a]] [[glossary:downregulation]]; tolerance to the [[glossary:head-twitch-response|head twitch response]] is observed after repeated dosing, with single-dose tolerance detectable at 24 hours{{cite|doi=10.1021/acschemneuro.2c00170|anchor=518a4032}}. [[glossary:cross-tolerance]] between serotonergic psychedelics has been documented{{cite|doi=10.1021/acschemneuro.2c00170|anchor=00b20e44}}. No [[glossary:physical-dependence]], compulsive use pattern, dose-escalation syndrome, or [[glossary:withdrawal]] has been documented for bufotenine or yopo{{cite|doi=10.1124/pharmrev.120.000056|anchor=373f6141}}. The 5-HT₂A downregulation mechanism makes self-escalating use pharmacologically self-limiting. Traditional cultural frameworks further structure and limit use patterns{{cite|doi=10.1080/02791072.2011.566499|anchor=3fe2854a}}. ====Drug Interactions==== '''MAO-A inhibitors''' represent the most dangerous interaction class. [[substance:harmaline]] co-administration increases systemic [[substance:5-meo-dmt]] exposure 3.6–4.4-fold and bufotenine exposure 9.9-fold by inhibiting [[glossary:mao-a]] deamination — the primary metabolic inactivation pathway for all three seed alkaloids{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=26b35713}}{{cite|doi=10.1124/dmd.112.050724|anchor=c29fffa6}}. This includes botanical sources (''B. caapi'', Syrian rue) and pharmaceutical MAOIs (phenelzine, tranylcypromine, moclobemide). [[glossary:severity]]: '''severe'''{{cite|pubmed=20942780|anchor=dc378fb4}}. '''SSRIs and SNRIs''' present a dual risk: pharmacodynamic [[glossary:serotonergic-load]] addition raises [[glossary:serotonin-syndrome]] risk, while chronic SSRI-induced 5-HT₂A downregulation may blunt effects unpredictably. Severity: '''moderate to severe'''{{cite|doi=10.1208/s12248-008-9028-5|anchor=0d7312a1}}. '''CYP2D6 inhibitors''' (fluoxetine, paroxetine, bupropion) reduce 5-MeO-DMT conversion to bufotenine, altering alkaloid exposure in unpredictable ways. Severity: '''moderate'''{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=81892487}}{{cite|doi=10.1208/s12248-008-9028-5|anchor=7d438dfd}}. Additional [[glossary:serotonergic-drug|serotonergic agents]] — triptans, [[substance:tramadol]], [[substance:fentanyl]], linezolid — carry additive serotonin toxicity risk{{cite|doi=10.1208/s12248-008-9028-5|anchor=25611ea5}}. All severity classifications are based on pharmacokinetic mechanism from animal data and pharmacodynamic class effects. No clinical case report of serotonin syndrome from yopo combined with any pharmaceutical has been published. ====Contraindications==== '''MAO inhibitor co-administration''' is absolutely contraindicated due to multi-fold increases in alkaloid exposure and serotonin toxicity risk{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=0072dce5}}. '''Cardiovascular disease''' — including [[glossary:ischemia|ischemic]] heart disease, [[glossary:arrhythmia|arrhythmias]], and uncontrolled hypertension — is absolutely contraindicated given prominent cardiovascular [[effect:stimulation]] at psychoactive doses{{cite|doi=10.2174/1570159x13666141210222409|anchor=d752d550}}. '''Psychotic disorders or strong family history of psychosis''' are absolutely contraindicated; serotonergic psychedelics can precipitate or exacerbate psychotic episodes{{cite|doi=10.1124/pharmrev.120.000056|anchor=7586b4a3}}. '''Pregnancy''' is contraindicated; [[substance_class:chemical/tryptamine]] alkaloids are expected to cross the placenta based on structural properties{{flag|safety-citation-needed}}. '''Hepatic impairment''' may reduce MAO-A [[glossary:clearance]], increasing systemic alkaloid exposure{{flag|safety-citation-needed}}. '''SSRI or SNRI use''' requires taper and physician-supervised washout prior to use due to serotonin syndrome risk{{cite|doi=10.1208/s12248-008-9028-5|anchor=c5e59de8}}.

====Toxicity==== No human [[glossary:fatality]] attributed to yopo or bufotenine has been found in peer-reviewed literature. [[glossary:animal-model|Animal studies]] administering bufotenine daily for 21 days found dose-dependent behavioral changes but no organ damage at lower doses; the alkaloid accumulated in the heart and kidney, and at higher doses in the lungs and brain{{cite|doi=10.1155/2018/1032638|anchor=1cf62a33}}. Cardiovascular effects are clinically significant at psychoactive doses: [[glossary:tachycardia]], [[glossary:hypertension]], intense [[effect:vasoconstriction]], facial purpling, chest heaviness, and [[effect:respiratory-stimulation]] have been documented in historical human administration studies{{flag|safety-citation-needed}}. [[effect:nausea]] and [[effect:vomiting]] are near-universal, triggered by [[glossary:serotonin]] [[glossary:receptor-activation]] in the gut{{cite|doi=10.2174/1570159x13666141210222409|anchor=6c5a27fb}}. No published studies examine [[glossary:contamination|contaminant]] profiles — pesticides, heavy metals, mycotoxins, or microbial load — in commercially sold seeds or prepared snuff. Alkaloid concentrations vary substantially by provenance, and no standardized testing requirement exists for this market. ====Psychological Risks==== [[glossary:rapid-onset]] and intense perceptual [[glossary:disruption]] create a high risk of acute [[effect:anxiety]] and panic, especially for unprepared individuals outside ritual contexts. The risk of acute [[glossary:psychotic-episodes]] is elevated in people with a personal or family history of psychotic [[glossary:disorder|disorders]]{{cite|doi=10.1124/pharmrev.120.000056|anchor=e6657c55}}. Persistent visual [[glossary:disturbance|disturbances]] after the experience ends ([[glossary:hppd]]) are a documented risk of serotonergic [[substance_class:psychoactive/psychedelic]] use; yopo-specific risk has not been studied but is extrapolated from [[substance:lsd]] and psilocybin data{{cite|doi=10.1007/s00213-022-06066-z|anchor=8d275766}}. ====Tolerance & Dependence==== No [[glossary:physical-dependence]], compulsive use pattern, or [[glossary:withdrawal]] has been documented for bufotenine or yopo{{cite|doi=10.1124/pharmrev.120.000056|anchor=262e8cd5}}. Serotonin [[glossary:downregulation]] after each dose makes [[glossary:tolerance]] build quickly{{cite|doi=10.1021/acschemneuro.2c00170|anchor=b782dbbd}} — this is why self-escalating use is pharmacologically self-limiting. [[glossary:cross-tolerance]] with psilocybin, LSD, and other [[glossary:serotonergic-psychedelics]] is established{{cite|doi=10.1021/acschemneuro.2c00170|anchor=71620fbb}}. Traditional cultural frameworks further structure and limit use patterns{{cite|doi=10.1080/02791072.2011.566499|anchor=1f3b23d6}}. ====Drug Interactions==== '''MAO-A inhibitors''' are the most dangerous interaction class. [[substance:harmaline]] blocks the body's primary pathway for breaking down the seed alkaloids, raising bufotenine exposure 9.9-fold{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=dfe17be7}}{{cite|doi=10.1124/dmd.112.050724|anchor=10577615}} and creating conditions for a potentially fatal serotonergic reaction. This includes pharmaceutical MAOIs (phenelzine, tranylcypromine, moclobemide) and botanical sources (''B. caapi'', Syrian rue). [[glossary:severity]]: '''severe'''{{cite|pubmed=20942780|anchor=4cfea8e2}}. '''SSRIs and SNRIs''' add [[glossary:serotonergic-load]], raising the risk of a dangerous overheating and [[glossary:seizure]] response. Chronic SSRI use also downregulates the serotonin [[glossary:receptor]] bufotenine targets, potentially blunting effects in unpredictable ways. Severity: '''moderate to severe'''{{cite|doi=10.1208/s12248-008-9028-5|anchor=153fac72}}. '''CYP2D6 inhibitors''' (fluoxetine, paroxetine, bupropion) reduce the conversion of [[substance:5-meo-dmt]] into bufotenine, altering alkaloid exposure unpredictably. Severity: '''moderate'''{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=9fc903ca}}{{cite|doi=10.1208/s12248-008-9028-5|anchor=0363e4fd}}. Additional [[glossary:serotonergic-drug|serotonergic agents]] — triptans, [[substance:tramadol]], [[substance:fentanyl]], linezolid — carry additive [[glossary:serotonin-syndrome]] risk{{cite|doi=10.1208/s12248-008-9028-5|anchor=a50a55cb}}. All severity classifications are based on animal data and pharmacodynamic class effects. No clinical [[glossary:case-report]] of serotonin syndrome from yopo combined with any pharmaceutical has been published. ====Contraindications==== '''MAO inhibitor co-administration''' is absolutely contraindicated — multi-fold increases in alkaloid exposure make serotonin toxicity risk severe{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=9b2dd23a}}. '''Cardiovascular disease''' — [[glossary:ischemia|ischemic]] heart disease, [[glossary:arrhythmia|arrhythmias]], uncontrolled hypertension — is absolutely contraindicated given prominent cardiovascular [[effect:stimulation]] at psychoactive doses{{cite|doi=10.2174/1570159x13666141210222409|anchor=0e33ee92}}. '''Psychotic disorders or strong family history of psychosis''' are absolutely contraindicated; serotonergic psychedelics can [[glossary:trigger]] or worsen psychotic episodes{{cite|doi=10.1124/pharmrev.120.000056|anchor=f2079e63}}. '''Pregnancy''' is contraindicated; [[substance_class:chemical/tryptamine]] alkaloids are expected to cross the placenta{{flag|safety-citation-needed}}. '''Hepatic impairment''' may reduce [[glossary:mao-a]] [[glossary:clearance]], increasing systemic alkaloid exposure{{flag|safety-citation-needed}}. '''SSRI or SNRI use''' requires physician-supervised taper and washout before use due to serotonin syndrome risk{{cite|doi=10.1208/s12248-008-9028-5|anchor=39adfc18}}.

====Traditional alkaline snuff==== Seeds are toasted until they crack, ground to fine powder, and blended with an alkaline agent — typically calcium carbonate from snail shells or plant ash. The alkaline additive converts the alkaloids into free-base form for efficient [[glossary:absorption]] through nasal tissue{{cite|name=iceers-yopo|type=web|author=ICEERS|year=2023|title=Yopo: Basic Info|anchor=2ac79ea8}}. The snuff is blown into the nose through a long tube by an assistant, or self-administered through a Y-shaped tube{{cite|pubmed=12422937|anchor=be6dd70c}}. Onset: 1–5 minutes{{cite|name=iceers-yopo|type=web|author=ICEERS|year=2023|title=Yopo: Basic Info|anchor=72c72c99}}. Duration: 20–60 minutes. [[effect:nausea]] and [[effect:vomiting]] are near-universal at psychoactive doses. This is the traditional and most widely documented preparation. ====Vaporized free-base bufotenine==== Purified or semi-purified bufotenine in free-base form can be vaporized and inhaled. [[glossary:active-dose|Active doses]] are reported at 2–8 mg{{flag|citation-needed}} — substantially lower than the snuff route, suggesting more efficient pulmonary absorption. Onset is near-instantaneous. Duration is comparable: 20–60 minutes. No published pharmacokinetic data exist for this route. ====MAO-inhibitor admixture==== Some indigenous traditions, notably the Piaroa of southern Venezuela, combine yopo with ''Banisteriopsis caapi'' or consume it prior to [[glossary:insufflation]]{{cite|pubmed=12422937|anchor=e7434ba3}}. The [[substance:harmine]] and [[substance:harmaline]] in ''B. caapi'' block [[glossary:mao-a]] — the primary pathway for alkaloid breakdown — raising [[substance:5-meo-dmt]] exposure 3.6–4.4-fold and bufotenine exposure 9.9-fold in [[glossary:animal-model|animal models]]{{cite|doi=10.1124/dmd.112.050724|anchor=d3acaf83}}{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=b5a01d12}}. The resulting experience is longer, more intense, and carries substantially greater [[glossary:serotonin-syndrome]] risk. This combination is classified as '''severe''' for [[glossary:drug-interaction]] purposes. Per-preparation dose tiers, timelines, and [[glossary:bioavailability]] data are in the Dose · by preparation card on this page.

====Traditional alkaline snuff==== The traditional and most widely documented preparation. Seeds are toasted over low heat until they crack, ground to fine powder, and blended with an alkaline agent — typically calcium carbonate from snail shells or plant ash. The alkaline additive free-bases the [[substance_class:chemical/tryptamine]] alkaloids, converting them from their [[glossary:salt-form]] for efficient mucosal [[glossary:absorption]]{{cite|name=iceers-yopo|type=web|author=ICEERS|year=2023|title=Yopo: Basic Info|anchor=1b317bee}}. The snuff is [[glossary:insufflation|insufflated]] nasally, traditionally blown through a long tube by an assistant or self-administered via a Y-shaped tube{{cite|pubmed=12422937|anchor=ab01da9f}}. Onset occurs within 1–5 minutes{{cite|name=iceers-yopo|type=web|author=ICEERS|year=2023|title=Yopo: Basic Info|anchor=acb532cf}}. Duration is 20–60 minutes. [[effect:nausea]] and [[effect:vomiting]] are near-universal at psychoactive doses. The experience is intense and self-limiting; [[glossary:intensity]] [[glossary:peak|peaks]] within minutes and subsides rapidly. ====Vaporized free-base bufotenine==== Purified or semi-purified bufotenine in free-base form can be vaporized and inhaled. This route is reported active at 2–8 mg{{flag|citation-needed}}, substantially below the nasal snuff dose, suggesting higher [[glossary:bioavailability]] through pulmonary absorption. Onset is near-instantaneous. Duration is comparable to the snuff route (20–60 minutes). No published pharmacokinetic parameters exist for this route. ====MAO-inhibitor admixture==== Some indigenous traditions, notably the Piaroa of southern Venezuela, combine yopo with ''Banisteriopsis caapi'' cuttings or consume ''B. caapi'' prior to insufflation{{cite|pubmed=12422937|anchor=b038c091}}. The [[substance:harmine]] and [[substance:harmaline]] in ''B. caapi'' inhibit [[glossary:mao-a]], the primary [[glossary:degradation]] pathway for all three seed alkaloids{{cite|pubmed=20942780|anchor=39f297be}}. This increases [[glossary:systemic-exposure]] dramatically — harmaline co-administration raises [[substance:5-meo-dmt]] exposure 3.6–4.4-fold and bufotenine exposure 9.9-fold in [[glossary:animal-model|animal models]]{{cite|doi=10.1124/dmd.112.050724|anchor=36fa5da1}}{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=fc806be4}}. The resulting experience is longer, more intense, and carries substantially greater [[glossary:serotonin-syndrome]] risk. This combination is classified as '''severe''' for [[glossary:drug-interaction]] purposes. Per-preparation dose tiers, timelines, and bioavailability data are in the Dose · by preparation card on this page.

===Forms & Identification=== ''A. peregrina'' seeds are sold online as whole dried seeds, pre-ground powder, or prepared snuff. No Certificate of Analysis program or alkaloid content labeling requirement exists for any commercial product. Because bufotenine, [[substance:dmt]], and [[substance:5-meo-dmt]] concentrations vary dramatically by seed provenance and maturity, identical-looking seeds from different batches may produce substantially different experiences. [[glossary:reagent-kit|Reagent testing]] can confirm [[substance_class:chemical/tryptamine]] presence but cannot quantify individual alkaloid ratios. Starting with a small test dose from each new batch is the only reliable safeguard against unexpected [[glossary:potency]]. ===Set & Setting=== Yopo's [[glossary:rapid-onset]] and intense somatic effects — [[effect:nausea]], [[effect:vomiting]], cardiovascular [[effect:stimulation]] — make environment especially important. A calm, private, indoor setting with soft surfaces reduces injury risk during the disorienting onset phase. A sober, [[glossary:sitter|trusted companion]] should be present, ideally someone familiar with the substance and its somatic [[glossary:intensity]]. The companion's primary role is physical safety during the first 10 minutes, when nausea and perceptual [[glossary:disruption]] are most acute. Individuals experiencing significant [[effect:anxiety]], [[effect:depression]], or [[effect:emotional-lability]] should not use yopo. ===Guidelines=== {{Guideline}} * Start with a fraction of a typical dose from any new seed batch — alkaloid content is unstandardized and varies by provenance. * Have a basin or bag nearby; nausea and vomiting are near-universal and onset is rapid. * Do not use alone. A sober companion should be present for the duration. * Do not combine with [[substance_class:pharmacological/monoamine-oxidase-inhibitor|monoamine oxidase inhibitors]] (pharmaceutical or botanical) unless the pharmacokinetic consequences are fully understood — alkaloid exposure increases up to 9.9-fold. * Do not use if taking SSRIs, SNRIs, or any serotonergic [[glossary:medication]]. * Avoid use with any cardiovascular condition, including [[glossary:hypertension|uncontrolled hypertension]]. * Allow at minimum 7 days between sessions to permit [[glossary:5-ht2a]] [[glossary:receptor]] resensitization. * Ensure the alkaline preparation agent is food-grade calcium carbonate or verified plant ash — unidentified alkaline substitutes may introduce [[glossary:contamination|contaminants]]. {{/Guideline}} ===Emergency Response=== {{Emergency}} ====Recognizing an emergency==== * Sustained [[glossary:heart-rate]] above 150 bpm or [[glossary:chest-pain]] * Severe difficulty breathing * Blue or purple discoloration of lips or extremities beyond initial facial flushing * Unresponsiveness or [[glossary:loss-of-consciousness]] * Prolonged [[glossary:psychosis|psychotic symptoms]] (extreme [[glossary:agitation]], incoherent speech, [[glossary:self-harm]] behavior) persisting beyond 60 minutes ====Immediate steps==== * '''1.''' Stay with the person. Do not leave them alone. * '''2.''' Call emergency services if any red flag above is present. * '''3.''' Place the person in a [[glossary:recovery-position]] if they are vomiting and unable to sit upright. * '''4.''' Monitor breathing and pulse continuously. * '''5.''' Keep the environment calm — reduce noise, dim lights, speak in short reassuring statements. ====What to tell the dispatcher==== State: "This person has inhaled a tryptamine-containing plant snuff (yopo). Estimated dose: [amount]. Time of administration: [time]. Symptoms: [describe]." [[glossary:good-samaritan-law|Good Samaritan laws]] protect callers from [[glossary:prosecution]] in many jurisdictions. ====Reversal agents==== No specific reversal agent exists for bufotenine or tryptamine [[substance_class:psychoactive/psychedelic|psychedelics]]. Treatment is supportive. [[substance_class:chemical/benzodiazepine|Benzodiazepines]] may be administered by medical personnel for severe agitation. {{/Emergency}} ===Aftercare & Integration=== {{Aftercare}} The 1–2 hours following a yopo experience may include residual nausea, [[glossary:fatigue]], and emotional [[glossary:sensitivity]]. Hydrate and rest. Avoid operating vehicles or machinery for at least 2 hours after effects resolve. Nausea may persist beyond the psychoactive window — ginger tea or bland food can help settle the stomach. If distressing content arose during the experience, allow several days before attempting to interpret or analyze it. Persistent anxiety or perceptual [[glossary:disturbance|disturbances]] beyond 48 hours warrant professional consultation. {{/Aftercare}} ===Recovery & Support=== {{Recovery}} Yopo does not produce [[glossary:physical-dependence]], and compulsive use is rare due to the self-limiting [[glossary:tolerance]] mechanism and the intensity of somatic onset. Any pattern of escalating use frequency or use despite negative consequences warrants self-assessment. For individuals experiencing psychological difficulty after yopo use — persistent anxiety, [[effect:depersonalization]], or perceptual disturbances — professional support is available: * '''SAMHSA National Helpline''' (US): 1-800-662-4357 (free, confidential, 24/7) * '''Fireside Project''' (psychedelic [[glossary:peer-support]]): 62-FIRESIDE (623-473-7433) * '''Crisis Text Line''': Text HOME to 741741 [[glossary:therapist|Integration therapists]] with [[glossary:psychedelic-experience]] can provide structured processing for [[glossary:difficult-experience|difficult experiences]]. {{/Recovery}}

===Forms & Identification=== ''A. peregrina'' seeds are sold online as whole dried seeds, pre-ground powder, or prepared snuff. No Certificate of Analysis program, ISO-accredited laboratory testing standard, or alkaloid content labeling requirement exists for any commercial product. Because bufotenine, [[substance:dmt]], and [[substance:5-meo-dmt]] concentrations vary dramatically by seed provenance and maturity, identical-looking seeds from different batches may produce substantially different experiences. [[glossary:reagent-kit|Reagent testing]] can confirm [[substance_class:chemical/tryptamine]] presence but cannot quantify individual alkaloid ratios. This means dosing decisions carry inherent uncertainty — starting with a small test dose from each new batch is the only reliable safeguard. ===Set & Setting=== Yopo's [[glossary:rapid-onset]] (1–5 minutes) and intense somatic effects — [[effect:nausea]], [[effect:vomiting]], cardiovascular [[effect:stimulation]] — make environment especially important. A calm, private, indoor setting with soft surfaces reduces injury risk during the disorienting onset phase. A sober, [[glossary:sitter|trusted companion]] should be present, ideally someone familiar with the substance and its somatic [[glossary:intensity]]. The companion's primary role is physical safety during the first 10 minutes, when nausea and perceptual [[glossary:disruption]] are most acute. Individuals experiencing significant [[effect:anxiety]], [[effect:depression]], or [[effect:emotional-lability]] should not use yopo. ===Guidelines=== {{Guideline}} * Start with a fraction of a typical dose from any new seed batch — alkaloid content is unstandardized and varies by provenance. * Have a basin or bag nearby; nausea and vomiting are near-universal and onset is rapid. * Do not use alone. A sober companion should be present for the duration. * Do not combine with [[substance_class:pharmacological/monoamine-oxidase-inhibitor|monoamine oxidase inhibitors]] (pharmaceutical or botanical) unless the pharmacokinetic consequences are fully understood — alkaloid exposure increases up to 9.9-fold. * Do not use if taking SSRIs, SNRIs, or any serotonergic [[glossary:medication]]. * Avoid use with any cardiovascular condition, including [[glossary:hypertension|uncontrolled hypertension]]. * Allow at minimum 7 days between sessions to permit [[glossary:5-ht2a]] [[glossary:receptor]] resensitization. * Ensure the alkaline preparation agent is food-grade calcium carbonate or verified plant ash — unidentified alkaline substitutes may introduce [[glossary:contamination|contaminants]]. {{/Guideline}} ===Emergency Response=== {{Emergency}} ====Recognizing an emergency==== * Sustained [[glossary:heart-rate]] above 150 bpm or [[glossary:chest-pain]] * Severe difficulty breathing * Blue or purple discoloration of lips or extremities beyond initial facial flushing * Unresponsiveness or [[glossary:loss-of-consciousness]] * Prolonged [[glossary:psychosis|psychotic symptoms]] (extreme [[glossary:agitation]], incoherent speech, [[glossary:self-harm]] behavior) persisting beyond 60 minutes ====Immediate steps==== * '''1.''' Stay with the person. Do not leave them alone. * '''2.''' Call emergency services if any red flag above is present. * '''3.''' Place the person in a [[glossary:recovery-position]] if they are vomiting and unable to sit upright. * '''4.''' Monitor breathing and pulse continuously. * '''5.''' Keep the environment calm — reduce noise, dim lights, speak in short reassuring statements. ====What to tell the dispatcher==== State: "This person has inhaled a tryptamine-containing plant snuff (yopo). Estimated dose: [amount]. Time of administration: [time]. Symptoms: [describe]." [[glossary:good-samaritan-law|Good Samaritan laws]] protect callers from [[glossary:prosecution]] in many jurisdictions. ====Reversal agents==== No specific reversal agent exists for bufotenine or tryptamine [[substance_class:psychoactive/psychedelic|psychedelics]]. Treatment is supportive. [[substance_class:chemical/benzodiazepine|Benzodiazepines]] may be administered by medical personnel for severe agitation. {{/Emergency}} ===Aftercare & Integration=== {{Aftercare}} The 1–2 hours following a yopo experience may include residual nausea, [[glossary:fatigue]], and emotional [[glossary:sensitivity]]. Hydrate and rest. Avoid operating vehicles or machinery for at least 2 hours after effects resolve. Nausea may persist beyond the psychoactive window — ginger tea or bland food can help settle the stomach. Emotional processing is common after intense [[glossary:psychedelic-experience|psychedelic experiences]]; journaling or quiet reflection is often more useful than immediate social engagement. If distressing content arose during the experience, allow several days before attempting to interpret or analyze it. Persistent anxiety or perceptual [[glossary:disturbance|disturbances]] beyond 48 hours warrant professional consultation. {{/Aftercare}} ===Recovery & Support=== {{Recovery}} Yopo does not produce [[glossary:physical-dependence]], and compulsive use is rare due to the self-limiting [[glossary:tolerance]] mechanism and the intensity of the somatic onset. However, any pattern of escalating use frequency or use despite negative consequences warrants self-assessment. For individuals experiencing psychological difficulty after yopo use — persistent anxiety, [[effect:depersonalization]], or perceptual disturbances — professional support is available: * '''SAMHSA National Helpline''' (US): 1-800-662-4357 (free, confidential, 24/7) * '''Fireside Project''' (psychedelic [[glossary:peer-support]]): 62-FIRESIDE (623-473-7433) * '''Crisis Text Line''': Text HOME to 741741 [[glossary:therapist|Integration therapists]] with psychedelic experience can provide structured processing for [[glossary:difficult-experience|difficult experiences]]. {{/Recovery}}

''A. peregrina'' occupies a legal gray area in most countries: the plant and seeds are not controlled under international treaty, but the alkaloids they contain are scheduled in most Western legal frameworks. Under the UN [[glossary:convention-on-psychotropic-substances]] (1971), [[substance:dmt]] is [[glossary:schedule-i]]; bufotenine and [[substance:5-meo-dmt]] are not internationally listed{{cite|name=un-convention-1971|type=legal|author=UNODC|year=1971|title=Convention on Psychotropic Substances 1971|anchor=766c8eea}}. In the United States, bufotenine ([[glossary:drug-enforcement-administration|DEA]] code 7433), DMT, and 5-MeO-DMT are all federally Schedule I — the seeds themselves are not listed, but [[glossary:possession]] with intent to extract alkaloids may [[glossary:trigger]] [[glossary:structural-analog]] provisions. In the United Kingdom, bufotenine and DMT are [[glossary:class-a]], carrying maximum penalties of 7 years for possession and life for supply. In Australia, all three alkaloids are Schedule 9 (Prohibited Substance). Venezuela constitutionally protects indigenous ceremonial use; Brazil and Colombia do not specifically control the seeds, though their scheduled alkaloids remain restricted{{flag|citation-needed}}. Across the European Union, [[glossary:member-state]] laws vary — bufotenine and DMT are generally controlled under national psychotropic substance laws, with no EU-wide harmonized scheduling of the plant. Legality depends on the specific national framework, the form of possession (seeds versus extracted alkaloids), and prosecutorial intent. {{Warning}} Legal status changes frequently. This overview reflects the status as of the article's last update and is not legal advice. Verify current law in the relevant jurisdiction before acting on this information. {{/Warning}}

''A. peregrina'' occupies a jurisdictional gray area: the plant and its seeds are not controlled under international treaty, but the alkaloids they contain — bufotenine, [[substance:dmt]], and [[substance:5-meo-dmt]] — are scheduled in most Western legal frameworks. Under the UN [[glossary:convention-on-psychotropic-substances]] (1971), DMT is [[glossary:schedule-i]], while bufotenine and 5-MeO-DMT are not listed{{cite|name=un-convention-1971|type=legal|author=UNODC|year=1971|title=Convention on Psychotropic Substances 1971|anchor=bd9b1347}}. Plants containing scheduled substances are explicitly excluded from [[glossary:international-control]] under this treaty. Legality depends on the specific national framework, the form of [[glossary:possession]] (seeds versus extracted alkaloids), and prosecutorial intent.

Jurisdiction	Classification	Key provisions
United States (federal)	Bufotenine: Schedule I (DEA 7433); DMT: Schedule I; 5-MeO-DMT: Schedule I	Seeds and plant material are not federally scheduled. Possession with intent to extract may trigger analog provisions under 21 U.S.C. § 813.
United Kingdom	Bufotenine: Class A; DMT: Class A	Maximum penalties: 7 years for possession, life for supply. Seeds not specifically listed; possession may be prosecuted if intent to produce a Class A drug is established.
Australia	Bufotenine, DMT, 5-MeO-DMT: Schedule 9 (Prohibited Substance)	Also listed under Criminal Code Regulations as controlled substances.
Venezuela	Indigenous ceremonial use constitutionally protected	LOPCI protects traditional use. Seeds are not controlled for traditional purposes{{flag|citation-needed}}.
Brazil	Seeds not federally controlled; DMT listed as prohibited (ANVISA)	Extracted bufotenine is not listed on Brazil's scheduled substances list as of last available review{{flag|citation-needed}}.
Colombia	Seeds not specifically controlled	Traditional indigenous use tolerated. Alkaloid scheduling requires jurisdiction-specific legal review{{flag|citation-needed}}.
European Union	Member state laws vary	Bufotenine and DMT are generally controlled under national psychotropic substance laws. No EU-wide harmonized scheduling of the plant or its alkaloids exists beyond the Convention framework.

====Analog and treaty considerations==== ''A. peregrina'' contains alkaloids that are scheduled in most Western jurisdictions while the plant itself is not internationally controlled. Extraction, concentration, or possession with intent to produce controlled alkaloids [[glossary:trigger|triggers]] criminal [[glossary:liability]] where those alkaloids are scheduled. Traditional ceremonial use is constitutionally protected in Venezuela; the legal status of traditional use in Brazil and Colombia should not be assumed as a defense without confirmed legal advice.

====Primary receptor targets==== Bufotenine is a [[glossary:5-ht2a]] [[glossary:agonist|receptor agonist]]. The 5-hydroxyl group on the [[substance_class:chemical/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 D155{{cite|doi=10.1016/j.ejmech.2024.117049|anchor=2849f00a}}. Bufotenine elicits the [[glossary:head-twitch-response|head twitch response]] in [[glossary:rodent-model|rodents]], the validated behavioral proxy for hallucinogenic activity at 5-HT₂A{{cite|doi=10.1016/j.ejmech.2024.117049|anchor=5b2aeafa}}. Activity at [[glossary:5-ht2c]] has also been demonstrated, with lower [[glossary:selectivity]] than at 5-HT₂A{{cite|pubmed=8700116|anchor=d030aee9}}. Microiontophoretic studies in rats demonstrated that bufotenine, like [[substance:lsd]], specifically antagonizes [[glossary:serotonin]] excitatory effects on [[glossary:brainstem]] [[glossary:neuron|neurons]] — a proposed mechanism of [[glossary:psychotomimetic]] action distinct from direct cortical 5-HT₂A agonism{{cite|doi=10.1111/j.1476-5381.1974.tb09609.x|anchor=29ea588b}}. [[substance:5-meo-dmt]] shows primary [[glossary:affinity]] for [[glossary:5-ht1a]] over 5-HT₂A{{cite|doi=10.1038/s41586-024-07403-2|anchor=fb17b82e}}, contributing an [[substance_class:psychoactive/anxiolytic]] and [[substance_class:psychoactive/dissociative]] dimension to the overall pharmacological profile. [[substance:dmt]] acts as a 5-HT₁A/2A/2C agonist, [[glossary:sigma-1-receptor]] ligand, and [[glossary:taar1]] agonist{{cite|doi=10.1007/s00213-022-06065-0|anchor=6bb2dc28}}. All three alkaloids converge on the Gq/phosphoinositide [[glossary:hydrolysis]] cascade downstream of 5-HT₂A [[glossary:activation]] as the primary intracellular signaling pathway for [[substance_class:psychoactive/psychedelic]] effects{{cite|doi=10.1124/pharmrev.120.000056|anchor=b3fe6f22}}. ====CNS penetration==== Early human administration studies in the 1950s and 1960s attributed bufotenine's effects primarily to peripheral cardiovascular actions, questioning whether the molecule crossed the [[glossary:blood-brain-barrier]]{{flag|citation-needed}}. This controversy has been resolved by more recent evidence: chronic [[glossary:intraperitoneal]] administration in mice demonstrated bufotenine [[glossary:accumulation]] in brain tissue at doses of 1.05–2.1 mg/animal/day over 21 days{{cite|doi=10.1155/2018/1032638|anchor=44babe1f}}, and 5-HT₂A binding data with head twitch response confirmation establish central psychedelic activity{{cite|doi=10.1016/j.ejmech.2024.117049|anchor=32604a21}}. ====Metabolic pathways==== [[glossary:cyp2d6]] catalyzes O-demethylation of 5-MeO-DMT to bufotenine ''in vivo'', a clinically significant metabolic conversion affected by CYP2D6 [[glossary:genetic-polymorphism]]: [[glossary:poor-metabolizer|poor metabolizers]] (carrying CYP2D6*2 or *10 alleles) show 2.6–40-fold lower catalytic efficiency for this conversion{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=5d098700}}. [[glossary:mao-a]] is the primary deamination route for all three alkaloids, representing the dominant inactivation pathway{{cite|pubmed=20942780|anchor=feacd579}}. [[substance: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''{{cite|doi=10.1124/dmd.112.050724|anchor=159339ea}}. ====Pharmacokinetics by route==== Via [[glossary:insufflation|intranasal]] insufflation (the traditional route), onset occurs within 1–5 minutes. Alkaline ash free-basing is essential for efficient mucosal [[glossary:absorption]]; without alkalinization, absorption is substantially reduced{{cite|name=iceers-yopo|type=web|author=ICEERS|year=2023|title=Yopo: Basic Info|anchor=0a3fa044}}. No published human pharmacokinetic studies exist with quantified T''max'', C''max'', or [[glossary:half-life]] for bufotenine via any route. 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{{cite|doi=10.1155/2018/1032638|anchor=bfa9868c}}. Vaporized free-base bufotenine is reported active at 2–8 mg{{flag|citation-needed}}, substantially below the nasal snuff [[glossary:dose-range]], suggesting higher [[glossary:bioavailability]] through pulmonary absorption. Specific pharmacokinetic parameters for this route have not been published. The combination with [[substance_class:pharmacological/monoamine-oxidase-inhibitor|monoamine oxidase inhibitors]] fundamentally alters the pharmacokinetic profile: [[glossary:inhibition]] of MAO-A deamination dramatically increases exposure to all three alkaloids, while [[glossary:modulation]] of CYP2D6-mediated conversion shifts the 5-MeO-DMT-to-bufotenine ratio{{cite|doi=10.1124/dmd.112.050724|anchor=c3997ad1}}{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=b75c5350}}{{cite|pubmed=20942780|anchor=1559d00c}}. No neuroimaging studies (fMRI, PET, EEG) with ''A. peregrina'' or yopo snuff as administered have been published.

The yopo experience is distinguished from most [[glossary:serotonergic-psychedelics|classical psychedelics]] by its compressed temporal profile and the prominence of its somatic dimension. [[effect:nausea]], [[effect:vomiting]], and intense cardiovascular [[effect:stimulation]] are not [[glossary:adverse-effects]] but integral components of the experience at psychoactive doses — they precede and overlap with the perceptual and cognitive effects, shaping the overall character of the state. The preparation method is the primary modifier: traditionally prepared alkaline snuff produces a rapid, intense, self-limiting experience; vaporized free-base bufotenine is active at a fraction of the snuff dose; and admixture with [[glossary:monoamine-oxidase]]-inhibiting plants creates a pharmacologically distinct experience of greater duration and [[glossary:intensity]]. [[glossary:set-and-setting]] [[glossary:sensitivity]] is high, and traditional ritual context is reported to substantially modulate psychological outcomes. Pharmacologically, yopo occupies a position between smoked [[substance:dmt]] and oral [[substance:ayahuasca]]. The dominant action of bufotenine at [[glossary:5-ht2a]] places it squarely in the classical [[substance_class:psychoactive/psychedelic]] category alongside psilocybin and DMT, but its compressed duration (20–60 minutes), prominent peripheral serotonergic effects, and the somatic intensity of its onset distinguish it from longer-acting oral [[substance_class:chemical/tryptamine|tryptamines]]. The nearest pharmacological comparator is vaporized DMT, which shares the [[glossary:rapid-onset]] and short duration, though the alkaloid profiles and [[glossary:receptor]] selectivities of the two preparations differ.

===Toxicity=== No human [[glossary:lethal-dose|LD₅₀]] for bufotenine has been published. No human [[glossary:fatality]] attributed specifically to yopo snuff or bufotenine has been identified in peer-reviewed literature. 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 safe{{cite|doi=10.1155/2018/1032638|anchor=ba37d344}}. The alkaloid was detected in heart and kidney at all doses and in lungs and brain at higher doses{{cite|doi=10.1155/2018/1032638|anchor=8cc59af2}}. Cardiovascular effects are prominent and clinically significant at psychoactive doses. Historical human administration studies of bufotenine (Fabing and Hawkins, 1956; Turner and Merlis, 1959) documented [[glossary:tachycardia]], [[glossary:hypertension]], intense [[effect:vasoconstriction|peripheral vasoconstriction]] with purpling and cyanosis of the face and neck, chest heaviness, and increased respiratory rate{{flag|safety-citation-needed}}. [[effect:nausea]] and [[effect:vomiting]] are nearly universal at psychoactive doses, mediated by peripheral serotonin₃ and 5-HT₄ [[glossary:receptor-activation]] in the gastrointestinal tract{{cite|doi=10.2174/1570159x13666141210222409|anchor=0a07d8fb}}{{flag|additional-citations-needed}}. ====Contaminant and adulterant risk==== No published analytical studies exist examining [[glossary:contamination|contaminant]] profiles — pesticide residues, heavy metals (lead, cadmium, arsenic, mercury), mycotoxins, or microbial load — in commercially sold ''A. peregrina'' seeds or prepared yopo snuff. Seeds are sold online without standardized alkaloid content testing; alkaloid concentrations vary substantially by provenance and maturity. Preparation with unverified alkaline ash substitutes may introduce additional variable contaminants. No testing standard, Certificate of Analysis requirement, or ISO/IEC-accredited laboratory program exists for this market. This represents a significant and entirely unstudied safety gap. ===Psychological risks=== Acute [[effect:anxiety]] and panic are high-risk outcomes outside traditional ritual contexts. The [[glossary:rapid-onset]] (1–5 minutes) and intense perceptual [[glossary:disruption]] can produce [[glossary:distress|acute distress]], particularly for unprepared individuals. Bufotenine is [[glossary:psychotomimetic]] at psychoactive doses; the risk of acute [[glossary:psychotic-episodes]] is elevated in individuals with personal or family history of psychotic [[glossary:disorder|disorders]]{{cite|doi=10.1124/pharmrev.120.000056|anchor=11b3636f}}{{flag|additional-citations-needed}}. [[effect:delirium]] may occur at very high doses, consistent with the classical [[substance_class:psychoactive/psychedelic]] [[glossary:toxidrome]]. [[glossary:hppd|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 [[substance:lsd]] and psilocybin data{{cite|doi=10.1007/s00213-022-06066-z|anchor=490ea3cd}}{{flag|additional-citations-needed}}. No peer-reviewed [[glossary:case-report|case reports]] of adverse psychiatric events specific to yopo snuff have been identified. Anxiety, panic, and psychotic episodes are reported anecdotally in non-traditional use contexts but lack published [[glossary:case-series]] documentation. ===Tolerance and dependence=== [[glossary:serotonergic-psychedelics|Classical serotonergic psychedelics]] produce rapid [[glossary:tolerance]] via [[glossary:5-ht2a]] [[glossary:downregulation]] in the frontal [[glossary:cortex]]; tolerance to the [[glossary:head-twitch-response|head twitch response]] is observed after repeated 4-day dosing, with single-dose tolerance detectable at 24 hours{{cite|doi=10.1021/acschemneuro.2c00170|anchor=97c38822}}. [[glossary:cross-tolerance]] between serotonergic psychedelics (demonstrated between LSD and [[substance:doi]]) has been documented{{cite|doi=10.1021/acschemneuro.2c00170|anchor=63eaf698}}. No bufotenine-specific tolerance studies have been published; the tolerance profile is extrapolated from the class mechanism. Classical psychedelics are characterized as having very low physical dependence potential. No compulsive use syndrome, dose-escalation pattern, or [[glossary:withdrawal]] has been documented for bufotenine or yopo{{cite|doi=10.1124/pharmrev.120.000056|anchor=dbae2b86}}. The 5-HT₂A downregulation mechanism makes self-escalating use pharmacologically self-limiting. Traditional cultural frameworks among indigenous communities further structure and limit use patterns{{cite|doi=10.1080/02791072.2011.566499|anchor=be251de6}}. ===Drug interactions=== The most dangerous interaction class involves [[glossary:mao-a]] [[glossary:inhibitor|inhibitors]]. [[substance:harmaline]] co-administration increases systemic [[substance:5-meo-dmt]] exposure 3.6–4.4-fold and bufotenine exposure 9.9-fold in [[glossary:animal-model|animal models]], through [[glossary:inhibition]] of MAO-A deamination — the primary metabolic inactivation pathway for all three seed alkaloids{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=a2c3ff7a}}{{cite|doi=10.1124/dmd.112.050724|anchor=496f651e}}. This class includes botanical sources (''B. caapi'', Syrian rue) and pharmaceutical MAOIs (phenelzine, tranylcypromine, moclobemide). The interaction is classified as '''severe''' based on the magnitude of pharmacokinetic change and the mechanism of [[glossary:serotonin-syndrome]] risk{{cite|pubmed=20942780|anchor=38790c5b}}. SSRIs and SNRIs present a dual risk: pharmacodynamic addition of [[glossary:serotonergic-load]] raises serotonin syndrome risk, while chronic SSRI-induced 5-HT₂A downregulation may blunt hallucinogenic effects unpredictably. This interaction is classified as '''moderate to severe''' based on pharmacodynamic mechanism; no clinical case report specific to yopo exists{{cite|doi=10.1208/s12248-008-9028-5|anchor=6561097b}}{{flag|additional-citations-needed}}. [[glossary:cyp2d6]] inhibitors (fluoxetine, paroxetine, bupropion) reduce 5-MeO-DMT O-demethylation to bufotenine, altering the alkaloid exposure profile in unpredictable and potentially dangerous ways. This interaction is classified as '''moderate''' based on pharmacokinetic mechanism{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=e543fe2a}}{{cite|doi=10.1208/s12248-008-9028-5|anchor=6850509c}}. Additional [[glossary:serotonergic-drug|serotonergic agents]] — triptans, [[substance:tramadol]], [[substance:fentanyl]], linezolid — carry additive serotonin toxicity risk through [[glossary:pharmacodynamic-interaction]]{{cite|doi=10.1208/s12248-008-9028-5|anchor=b286093d}}{{flag|additional-citations-needed}}. All interaction [[glossary:severity]] classifications are based on pharmacokinetic mechanism from animal data and pharmacodynamic class effects. No clinical case report of serotonin syndrome from yopo combined with any pharmaceutical has been identified in the literature. ===Contraindications=== '''MAO inhibitor co-administration''' is absolutely contraindicated due to severe [[glossary:pharmacokinetic-interaction]] producing multi-fold increases in alkaloid exposure and serotonin toxicity risk{{cite|doi=10.1016/j.bcp.2010.02.020|anchor=4afc211e}}{{flag|additional-citations-needed}}. '''Cardiovascular disease''' — including [[glossary:ischemia|ischemic]] heart disease, [[glossary:arrhythmia|arrhythmias]], and uncontrolled hypertension — is absolutely contraindicated given the prominent cardiovascular [[effect:stimulation]] (tachycardia, hypertension, peripheral vasoconstriction) documented at psychoactive doses{{cite|doi=10.2174/1570159x13666141210222409|anchor=3356144b}}{{flag|additional-citations-needed}}. '''Psychotic disorders or strong family history of psychosis''' constitute an absolute [[glossary:contraindication]]; serotonergic psychedelics can precipitate or exacerbate psychotic episodes in predisposed individuals{{cite|doi=10.1124/pharmrev.120.000056|anchor=3c23bccb}}{{flag|additional-citations-needed}}. '''Pregnancy''' is contraindicated in the absence of published safety data; [[substance_class:chemical/tryptamine]] alkaloids are expected to cross the placenta based on structural properties and molecular weight{{flag|safety-citation-needed}}. '''Hepatic impairment''' may reduce MAO-A [[glossary:clearance]] of the alkaloids, increasing systemic exposure; no substance-specific data exist to quantify this risk{{flag|safety-citation-needed}}. '''SSRI or SNRI use''' requires taper and physician-supervised washout prior to yopo administration due to serotonin syndrome risk and unpredictable pharmacodynamic interaction{{cite|doi=10.1208/s12248-008-9028-5|anchor=2cf33e5b}}{{flag|additional-citations-needed}}.

Under the UN [[glossary:convention-on-psychotropic-substances]] (1971), [[substance:dmt]] is listed as [[glossary:schedule-i]]{{cite|name=un-convention-1971|type=legal|author=UNODC|year=1971|title=Convention on Psychotropic Substances 1971|anchor=2b7a558f}}. Bufotenine and [[substance:5-meo-dmt]] are not listed under this convention. Plants containing scheduled substances are explicitly not subject to [[glossary:international-control]] under the 1971 Convention framework. The 1961 Single Convention on Narcotic Drugs and the 1988 Convention against Illicit Traffic do not apply to ''A. peregrina''. The plant therefore occupies a legal gray area in most jurisdictions: the [[glossary:plant-material]] is not internationally controlled, but its constituent alkaloids (bufotenine, DMT, 5-MeO-DMT) are scheduled in many national frameworks.

Jurisdiction	Classification	Key provisions
United States (federal)	Bufotenine: Schedule I (DEA code 7433); DMT: Schedule I; 5-MeO-DMT: Schedule I	''A. peregrina'' seeds and plant material are not federally scheduled. Possession with intent to extract scheduled alkaloids may trigger federal analog provisions under 21 U.S.C. § 813. No state-level analog statutes specifically targeting yopo have been identified.
United Kingdom	Bufotenine: Class A; DMT: Class A (Misuse of Drugs Act 1971)	Maximum penalties: 7 years for possession, life for supply. Seeds are not specifically listed; possession may be prosecuted if intent to produce a Class A drug is established.
Australia	Bufotenine: Schedule 9 (Prohibited Substance); DMT and 5-MeO-DMT: Schedule 9	Poisons Standard classification; also listed under Criminal Code Regulations as controlled substances.
Venezuela	Indigenous ceremonial use constitutionally protected	Organic Law on Indigenous Peoples and Communities (LOPCI) protects traditional use. ''A. peregrina'' seeds are not controlled for traditional purposes{{flag|citation-needed}}.
Brazil	Seeds not federally controlled; DMT listed by ANVISA as prohibited	Extracted bufotenine is not listed on Brazil's scheduled substances list as of last available review{{flag|citation-needed}}.
Colombia	Seeds not specifically controlled	Traditional indigenous use tolerated. Alkaloid scheduling requires jurisdiction-specific legal review{{flag|citation-needed}}.
European Union	Member state laws vary	Bufotenine and DMT are generally controlled under national psychotropic substance laws implementing the 1971 Convention. Individual member state schedules require case-by-case verification; no EU-wide harmonized scheduling of the plant or its alkaloids exists beyond the Convention framework.

====Analog and treaty considerations==== ''A. peregrina'' contains alkaloids (bufotenine, DMT) that are scheduled in most Western jurisdictions, while the plant itself is not controlled under international treaty. Extraction, concentration, or [[glossary:possession]] with intent to produce controlled alkaloids would [[glossary:trigger]] criminal [[glossary:liability]] in jurisdictions where the alkaloids are scheduled. Traditional and ceremonial use is constitutionally protected in Venezuela; the legal status of traditional use in Brazil and Colombia requires jurisdiction-specific legal review and should not be assumed as a defense in the absence of confirmed legal advice.