Banisteriopsis caapi
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'''Banisteriopsis caapi''' (Malpighiaceae) — caapi, yagé, [[substance:ayahuasca]] vine — is a woody Amazonian liana whose bark and stems are brewed into psychoactive preparations. Its alkaloids are β-carbolines, dominated by [[substance:harmine]], which block [[glossary:mao-a]] — the [[glossary:enzyme]] that breaks down [[glossary:serotonin]]. Combined with a [[substance:dmt]]-containing plant, this [[glossary:blockade]] allows DMT to survive digestion and reach the brain.
Amazonian indigenous peoples have used B. caapi in ceremony and healing for millennia{{cite|doi=10.3390/plants14071149|anchor=bc2de89d}}. The 1996 Hoasca Project provided the first human pharmacokinetic data for ritual ayahuasca{{cite|pubmed=8889686|anchor=f0ab4e23}}, and 20th-century Brazilian syncretic religions — Santo Daime and União do Vegetal — spread ceremonial use worldwide. Brazil has recognized religious ayahuasca use since 1987{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=f0cb9ffc}}, and a 2018 clinical trial found significant [[substance_class:psychoactive/antidepressant]] effects in treatment-resistant patients{{cite|doi=10.1017/s0033291718001356|anchor=ce7b921a}}.
[[index:effects|Subjective effects]] include vivid visual and [[effect:auditory-hallucinations]], [[effect:emotional-enhancement]], deep [[glossary:introspection]], and somatic [[glossary:intensity]]. Whether a DMT-containing admixture plant is present determines the experience's character — B. caapi alone produces mainly mild introspective and somatic effects, while classic ayahuasca produces a dense, multi-layered altered state. [[effect:nausea]] and [[effect:vomiting]] occur in most users{{cite|doi=10.1590/1516-4446-2020-0913|anchor=407c9bb3}} and are regarded as characteristic, not incidental.
No [[glossary:physical-dependence]] or [[glossary:withdrawal]] has been documented{{cite|doi=10.1371/journal.pone.0042421|anchor=903d36b6}}, and no autopsy has attributed death to ayahuasca alone{{cite|doi=10.3390/jcm11041147|anchor=59408ce0}}. The dominant risk is '''serotonin syndrome''' — a dangerous overheating and [[glossary:seizure]] response — when B. caapi's MAO-A blockade combines with serotonergic [[glossary:medication|medications]] like SSRIs{{cite|doi=10.3390/biom12111618|anchor=9e69cfe8}}. Nearly all clinical evidence derives from ayahuasca preparations containing a DMT admixture; no pharmacokinetic data exist for B. caapi-only preparations.
'''Banisteriopsis caapi''' (''Ayahuasca'', ''Caapi'', ''Yagé'') is a woody liana of the family Malpighiaceae, native to lowland Amazonian rainforest across Bolivia, Brazil, Colombia, Ecuador, Peru, and Venezuela. Its pharmacology is driven by three β-carboline alkaloids — [[substance:harmine]], [[substance:harmaline]], and tetrahydroharmine — which act as reversible [[glossary:mao-a]] (MAO-A) [[glossary:inhibitor|inhibitors]]. The vine is most commonly prepared as an oral decoction, either alone or combined with [[substance:dmt]]-containing admixture plants to produce the preparation known as [[substance:ayahuasca]], with effects lasting 4–6 hours.
B. caapi has been used for ceremonial, healing, and divinatory purposes by Amazonian indigenous peoples for millennia{{cite|doi=10.3390/plants14071149|anchor=b510ba69}}. Richard Spruce first collected the species in the 1850s; Grisebach described it as ''Banisteria caapi'', and Morton reclassified it to ''Banisteriopsis'' in 1931{{cite|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:29180-2|anchor=76ca044e}}. The 1996 Hoasca Project produced the first human [[glossary:plasma]] pharmacokinetic data{{cite|pubmed=8889686|anchor=e295e9dc}}, and a 2018 [[glossary:placebo-controlled-trial]] demonstrated significant rapid [[substance_class:psychoactive/antidepressant]] effects in treatment-resistant [[effect:depression]]{{cite|doi=10.1017/s0033291718001356|anchor=28308ceb}}. Religious use is legally protected in Brazil since 1987 and in the United States under a 2006 Supreme Court RFRA ruling{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=311559db}}.
Harmine, the dominant alkaloid (mean 4.79 mg/g dried liana, RSD 170%), is a potent reversible MAO-A inhibitor at low nanomolar concentrations{{cite|doi=10.3390/plants9070870|anchor=399ffa39}}{{cite|doi=10.1093/toxsci/kfaf118|anchor=b7abb253}}. In ayahuasca preparations, this [[glossary:inhibition]] prevents gastrointestinal and hepatic deamination of DMT from the admixture plant, enabling oral [[glossary:bioavailability]] of an otherwise orally inactive [[substance_class:chemical/tryptamine]]{{cite|pubmed=12660312|anchor=179cfe94}}. Tetrahydroharmine contributes secondary [[substance_class:pharmacological/serotonin-reuptake-inhibitor]], while harmaline provides weaker MAO-A inhibition{{cite|doi=10.3390/biom12111618|anchor=5d6f27c6}}.
When combined with a DMT source, B. caapi produces intense visual and auditory perceptual [[glossary:modification]], cognitive and emotional intensification, and pronounced [[effect:nausea]] and [[effect:vomiting]]. B. caapi alone reportedly produces somatic and introspective effects without intense visual [[glossary:hallucination|hallucinations]], though no published clinical data exist for this preparation. Alkaloid concentrations show extreme batch variability (RSD 78.9–170%), making preparation source the primary practical modifier{{cite|doi=10.3390/plants9070870|anchor=70a7095a}}.
The principal safety concern is MAO-A inhibition by harmine and harmaline, creating mechanistic risk for '''serotonin syndrome''' with concurrent serotonergic [[glossary:medication|medications]]{{cite|doi=10.3390/biom12111618|anchor=f939a62a}}. No post-mortem study has attributed [[glossary:fatality|lethality]] to ayahuasca alone{{cite|doi=10.3390/jcm11041147|anchor=2a22b23d}}. Long-term ritual users show no [[effect:cognitive-impairment]], [[glossary:physical-dependence]], or [[glossary:addiction]]-related problems{{cite|doi=10.1371/journal.pone.0042421|anchor=2fbbc53f}}. Acute psychological [[glossary:adverse-effects]] — [[effect:anxiety]], [[effect:confusion]], and panic — occur commonly, with elevated risk in individuals with psychotic or bipolar [[glossary:disorder]] history{{cite|doi=10.2174/1570159x16666180125095902|anchor=1c3df4a8}}. No systematic data exist on [[glossary:contamination|contaminant]] risk in commercial B. caapi products, and no [[glossary:withdrawal]] has been characterized.
'''Ayahuasca vine''' (''Banisteriopsis caapi'', Malpighiaceae) — caapi, yagé — is a woody liana native to Amazonian rainforest whose stems and bark are prepared as psychoactive decoctions. Its primary active constituents are β-carboline alkaloids, principally [[substance:harmine]], which act as potent reversible [[glossary:mao-a]] [[glossary:inhibitor|inhibitors]]. Harmine produces its principal effects by blocking monoamine oxidase A, preventing [[glossary:serotonin]] breakdown and — in combination preparations — enabling oral [[glossary:bioavailability]] of co-administered [[substance:dmt]].
B. caapi has been used for ceremonial and healing purposes by Amazonian indigenous peoples for millennia{{cite|doi=10.3390/plants14071149|anchor=d54a3cff}}. The 1996 Hoasca Project provided the first human pharmacokinetic data for ritual [[substance:ayahuasca]]{{cite|pubmed=8889686|anchor=65eca27f}}, and a 2018 trial demonstrated significant [[substance_class:psychoactive/antidepressant]] effects in treatment-resistant [[effect:depression]]{{cite|doi=10.1017/s0033291718001356|anchor=4768d4ad}}. Religious use is legally protected in Brazil since 1987 and in the United States under a 2006 Supreme Court ruling{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=06c23c0e}}.
When combined with a DMT-containing admixture plant, B. caapi produces intense visual and auditory perceptual [[glossary:modification]], cognitive amplification, emotional intensification, and deep [[glossary:introspection]]. The experience is distinctly multi-layered — a convergence of somatic, perceptual, and psychological effects shaped by set, setting, and ceremonial context. Pronounced [[effect:nausea]] and [[effect:vomiting]] are characteristic unsought effects, occurring in a majority of users{{cite|doi=10.1590/1516-4446-2020-0913|anchor=0438570b}}.
No [[glossary:physical-dependence]] or [[glossary:withdrawal]] has been documented; long-term ritual users show no [[effect:cognitive-impairment]] or [[glossary:addiction]]-related problems{{cite|doi=10.1371/journal.pone.0042421|anchor=45808770}}. The principal safety concern is MAO-A [[glossary:inhibition]] creating mechanistic risk for '''serotonin syndrome''' with concurrent serotonergic [[glossary:medication|medications]]{{cite|doi=10.3390/biom12111618|anchor=3c6c77ec}}. Clinical evidence derives almost entirely from ayahuasca preparations containing DMT admixture; no published pharmacokinetic data exist for B. caapi-only preparations.
===Traditional and historical use===
Amazonian indigenous peoples — Shipibo-Conibo, Shuar, Cofán, and others — have used B. caapi for ceremony, healing, and divination for millennia{{cite|doi=10.3390/plants14071149|anchor=4d70f9ee}}{{cite|doi=10.2174/1570159x16666180125095902|anchor=97cbd642}}. The vine was managed rather than domesticated. Preparation involves boiling pounded vine with [[substance:dmt]]-containing plants; healers called ''curanderos'' guide the session within a prescribed dietary regimen known as a ''dieta''{{cite|doi=10.3389/fphar.2016.00035|anchor=0b1724de}}.
===Western discovery and research===
Richard Spruce collected the vine during Amazonian expeditions in the 1850s{{flag|citation-needed}}; it was formally classified by Morton in 1931{{cite|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:29180-2|anchor=a0e48cf5}} and the ethnobotanical record consolidated by Schultes in 1957{{cite|name=schultes-1957|type=book|author=Schultes RE|year=1957|title=The Identity of the Malpighiaceous Narcotics of South America|anchor=3c331430}}. The 1996 Hoasca Project produced the first human pharmacokinetic data from ritual [[substance:ayahuasca]] use{{cite|pubmed=8889686|anchor=8744032b}}.
===Modern era===
Brazilian syncretic religions — '''Santo Daime''' (founded 1930s) and '''União do Vegetal''' (founded 1961) — spread ceremonial ayahuasca use globally{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=edc11b31}}. Brazil recognized religious use in 1987; Peru declared it national cultural heritage in 2008{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=c67ef216}}. A 2018 [[glossary:placebo-controlled-trial]] found significant [[substance_class:psychoactive/antidepressant]] effects in treatment-resistant [[effect:depression]]{{cite|doi=10.1017/s0033291718001356|anchor=eafe6b13}}.
===Traditional and historical use===
'''Banisteriopsis caapi''' has been used for ceremonial, healing, and divinatory purposes by numerous Amazonian indigenous peoples. Phylogenetic evidence supports millennia-old exchange of use among Amazonian populations, with no [[glossary:indication]] of human manipulation in the species' diversification — suggesting management of a [[glossary:naturally-occurring|naturally occurring]] plant rather than deliberate domestication{{cite|doi=10.3390/plants14071149|anchor=c0e8ec1a}}. Traditional names reflect broad geographic distribution: ''ayahuasca'' (Quechua: "vine of the soul"), ''caapi'' (Tupí), ''yajé'' or ''yagé'' (Colombian indigenous groups), and ''natema'' (Shuar). Documented user populations include the Shipibo-Conibo, Shuar, Siona-Secoya, Cofán, and many other Amazonian nations{{cite|doi=10.2174/1570159x16666180125095902|anchor=d946a5ce}}.
The traditional preparation involves extended boiling of pounded B. caapi vine stalks and bark, usually combined with leaves of ''Psychotria viridis'' or other [[substance:dmt]]-containing plants to produce the classic [[substance:ayahuasca]] decoction. ''Curanderos'' and ''vegetalistas'' (Mestizo-tradition healers) integrate B. caapi into healing practices alongside prescribed dietary regimens known as ''dietas''{{cite|doi=10.2174/1570159x16666180125095902|anchor=72560a7d}}{{cite|doi=10.3389/fphar.2016.00035|anchor=4d55ead5}}.
===Western discovery and research===
The British botanist Richard Spruce first collected B. caapi during Amazonian expeditions in the early 1850s{{flag|citation-needed}}. August Grisebach formally described the specimen as ''Banisteria caapi'', and Conrad Vernon Morton reclassified it to ''Banisteriopsis'' in 1931{{cite|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:29180-2|anchor=b7fd0bbe}}. Schultes consolidated the ethnobotanical record in 1957, establishing B. caapi's central role in Amazonian psychoactive plant use{{cite|name=schultes-1957|type=book|author=Schultes RE|year=1957|title=The Identity of the Malpighiaceous Narcotics of South America|anchor=e5054c47}}.
The '''Hoasca Project''' (1996) — a collaboration between McKenna, Callaway, Grob, and colleagues — measured harmala alkaloid and DMT [[glossary:plasma-concentration|plasma levels]] in 15 members of the Brazilian União do Vegetal church, producing the first human pharmacokinetic data for ritual ayahuasca{{cite|pubmed=8889686|anchor=82703f23}}. Riba and colleagues in Barcelona subsequently conducted the first [[glossary:double-blind]] [[glossary:placebo|placebo-controlled]] studies of ayahuasca in healthy volunteers{{cite|pubmed=12660312|anchor=dbcb9dd1}}{{cite|pubmed=16149336|anchor=51bef5f5}}.
===Modern era===
The 20th century saw the emergence of Brazilian syncretic religions centred on ayahuasca as a sacrament. '''Santo Daime''', founded by Raimundo Irineu Serra in the 1930s, and '''União do Vegetal''' (UDV), founded by José Gabriel da Costa in 1961, have exported ayahuasca ceremony to North America, Europe, and beyond{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=f34c97dd}}.
* 1987 — Brazil's CONAD formally recognized ayahuasca for religious use{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=d14120b3}}
* 2006 — US Supreme Court upheld RFRA exemption for UDV in ''Gonzales v. O Centro Espírita Beneficente União do Vegetal''{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=c82f2f0b}}
* 2008 — Peru declared ayahuasca part of national cultural heritage{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=13dd16a9}}
* 2018 — First placebo-controlled randomized trial demonstrated significant [[substance_class:psychoactive/antidepressant]] effects in treatment-resistant [[effect:depression]]{{cite|doi=10.1017/s0033291718001356|anchor=22711c0d}}
* 2023 — Church of Gaia received [[glossary:drug-enforcement-administration|DEA]] religious exemption for sacramental ayahuasca use in the United States{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=fa9b5a60}}
===Discovery and early record===
'''Banisteriopsis caapi''' was first collected by the British botanist Richard Spruce during his Amazonian expeditions in the early 1850s{{flag|citation-needed}}. The specimen was formally described by the German botanist August Grisebach as ''Banisteria caapi'' Spruce ex Griseb. In 1931, the American botanist Conrad Vernon Morton reclassified the species into the genus ''Banisteriopsis'', establishing the currently accepted binomial ''Banisteriopsis caapi'' (Spruce ex Griseb.) C.V.Morton, published in the ''Journal of the Washington Academy of Sciences''{{cite|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:29180-2|anchor=9f1d42e1}}. Schultes produced foundational ethnobotanical work in 1957 identifying B. caapi and related Malpighiaceae as the primary psychoactive plants of South America{{cite|name=schultes-1957|type=book|author=Schultes RE|year=1957|title=The Identity of the Malpighiaceous Narcotics of South America|anchor=8374de1e}}.
===Traditional use===
B. caapi has been used for ceremonial, healing, and divinatory purposes by numerous Amazonian indigenous peoples. Phylogenetic evidence supports millennia-old exchange of use among Amazonian populations, with no evidence of human manipulation in the species' diversification — indicating management of a [[glossary:naturally-occurring|naturally occurring]] plant rather than deliberate domestication{{cite|doi=10.3390/plants14071149|anchor=092bda1d}}. Traditional names reflect broad geographic distribution: ''ayahuasca'' (Quechua: "vine of the soul" or "vine of the dead"), ''caapi'' (Tupí), ''yajé'' or ''yagé'' (Colombian indigenous groups), and ''natema'' (Shuar). Documented user populations include the Shipibo-Conibo, Shuar, Siona-Secoya, Cofán, and numerous other Amazonian nations{{cite|doi=10.2174/1570159x16666180125095902|anchor=c8f744c0}}.
The traditional preparation involves extended boiling (typically 8–12+ hours) of pounded or mashed B. caapi vine stalks and bark, usually combined with leaves of ''Psychotria viridis'' or other [[substance:dmt]]-containing admixture plants. This two-plant combination constitutes the classic [[substance:ayahuasca]] decoction, though B. caapi-only preparations are also documented among some indigenous groups. ''Curanderos'' and ''vegetalistas'' (Mestizo-tradition healers) in the western Amazon integrate B. caapi into healing traditions alongside prescribed dietary regimens known as ''dietas''{{cite|doi=10.2174/1570159x16666180125095902|anchor=78152185}}{{cite|doi=10.3389/fphar.2016.00035|anchor=dc5b1bfa}}.
===Western encounter and research===
Spruce's botanical work brought B. caapi to Western scientific attention in the mid-19th century. Schultes consolidated the ethnobotanical record in 1957, establishing B. caapi's central role in Amazonian psychoactive plant use{{cite|name=schultes-1957|type=book|author=Schultes RE|year=1957|title=The Identity of the Malpighiaceous Narcotics of South America|anchor=a0993f59}}. The pharmacological significance of the vine was established in the late 20th century with the '''Hoasca Project''' (1996) — a collaboration between McKenna, Callaway, Grob, and colleagues that measured DMT and harmala alkaloid [[glossary:plasma-concentration|plasma levels]] in 15 members of the Brazilian União do Vegetal (UDV) church, producing the first published human [[glossary:plasma]] pharmacokinetic data for ritual ayahuasca [[glossary:ingestion]]{{cite|pubmed=8889686|anchor=ed42058f}}. Riba and colleagues in Barcelona subsequently conducted the first [[glossary:double-blind]] [[glossary:placebo|placebo-controlled]] clinical pharmacology studies of encapsulated ayahuasca in healthy volunteers{{cite|pubmed=12660312|anchor=7a55b887}}{{cite|pubmed=16149336|anchor=71efa775}}.
===Brazilian syncretic churches===
The 20th century saw the emergence of Brazilian syncretic religions using ayahuasca as a sacrament. '''Santo Daime''', founded by Raimundo Irineu Serra in the 1930s, and '''União do Vegetal''' (UDV), founded by José Gabriel da Costa in 1961, both center their ritual practice on ayahuasca consumption. These movements have exported ayahuasca ceremony to North America, Europe, and other regions{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=a2eab5e4}}.
===Regulatory milestones===
* 1987 — Brazil's CONAD (National Council on Drug Policy) formally recognized ayahuasca for religious use{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=a3ec5ac1}}
* 1996 — Hoasca Project published first human plasma pharmacokinetic data for ritual ayahuasca ingestion{{cite|pubmed=8889686|anchor=91c58786}}
* 2006 — US Supreme Court upheld RFRA exemption for UDV church ayahuasca use in ''Gonzales v. O Centro Espírita Beneficente União do Vegetal''{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=14f02a3e}}
* 2008 — Peru declared ayahuasca part of national cultural heritage{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=f3957573}}
* 2010 — Brazil CONAD issued clarifying resolution for religious ayahuasca use{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=fa86a7b5}}
* 2018 — First placebo-controlled randomized trial demonstrated significant [[substance_class:psychoactive/antidepressant]] effects in treatment-resistant [[effect:depression]]{{cite|doi=10.1017/s0033291718001356|anchor=66ae402c}}
* 2023 — Church of Gaia received [[glossary:drug-enforcement-administration|DEA]] religious exemption for sacramental ayahuasca use in the United States{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=b650288b}}
| Family | Malpighiaceae |
| Genus | ''Banisteriopsis'' |
| Species | ''Banisteriopsis caapi'' (Spruce ex Griseb.) C.V.Morton |
| Native range | South Tropical America: Bolivia, Brazil (North, West-Central), Colombia, Ecuador, Peru, Venezuela, Argentina (Northwest) |
| Cultivation status | Both wild-harvested and cultivated |
| POWO accepted name | ''Banisteriopsis caapi'' (Spruce ex Griseb.) C.V.Morton{{cite|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:29180-2|anchor=612b9f1b}} |
'''Banisteriopsis caapi''' (Spruce ex Griseb.) C.V.Morton belongs to the family Malpighiaceae. Originally described as ''Banisteria caapi'' by Grisebach, it was reclassified into ''Banisteriopsis'' by Morton in 1931{{cite|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:29180-2|anchor=e2c63d2b}}. Indigenous growers recognize multiple cultivar varieties distinguished by bark colour and stem diameter, though formal subspecies classification is not well established.
The vine grows across the lowland tropical rainforests of Bolivia, Brazil, Colombia, Ecuador, Peru, and Venezuela. It thrives in moist, shaded conditions, climbing canopy trees on large woody stems that can reach several centimetres in diameter. B. caapi is actively cultivated by indigenous communities and at [[substance:ayahuasca]] retreat sites; wild populations face pressure from Amazonian deforestation but the species is not considered endangered.
B. caapi has smooth to lightly fissured bark, opposite ovate leaves, and small pink to pale flowers. A distinctive cross-section pattern in the woody stem — sometimes described as a "ladder" or "staircase" — helps indigenous harvesters distinguish it from similar Malpighiaceae lianas growing in the same forest.
'''Banisteriopsis caapi''' (Spruce ex Griseb.) C.V.Morton is a large woody liana (climbing vine) of the family Malpighiaceae. Originally described as ''Banisteria caapi'' by Grisebach, it was reclassified into the genus ''Banisteriopsis'' by Morton in 1931{{cite|url=https://powo.science.kew.org/taxon/urn:lsid:ipni.org:names:29180-2|anchor=c9feac26}}. Multiple cultivar varieties are recognized by indigenous growers — distinguished primarily by bark colour, stem diameter, and growth habit — though formal taxonomic subdivision below the species level is not well established.
The vine is native to lowland tropical rainforest across Bolivia, Brazil, Colombia, Ecuador, Peru, and Venezuela. It thrives in moist, shaded conditions, climbing canopy trees as a large woody stem that can reach several centimetres in diameter and extend high into the forest canopy. B. caapi is actively cultivated throughout its native range by indigenous communities and at [[substance:ayahuasca]]-retreat sites; wild populations are affected by broader Amazonian habitat loss but the species is not considered endangered.
B. caapi is identified by smooth to lightly fissured bark, opposite ovate leaves, and clusters of small pink to pale flowers. A distinctive cross-section pattern — sometimes described as a "ladder" or "staircase" motif in the woody interior — is used by indigenous harvesters to distinguish B. caapi from superficially similar Malpighiaceae lianas in the same habitat.
For psychoactive preparation, sections of mature stem and bark are harvested and typically pounded or shredded to expose inner tissue before boiling. Stem age and harvest timing influence alkaloid content; further preparation details are covered in the Preparations section.
[[substance:harmine]] is the dominant alkaloid in B. caapi, present at a mean concentration of 4.79 mg/g dried vine{{cite|doi=10.3390/plants9070870|anchor=69985b69}}. It reversibly blocks [[glossary:mao-a]] at very low concentrations{{cite|doi=10.1093/toxsci/kfaf118|anchor=019e6c6f}}, raising [[glossary:serotonin]] levels and — in [[substance:ayahuasca]] preparations — preventing the gut from destroying [[substance:dmt]], making it orally active{{cite|pubmed=12660312|anchor=e56c4610}}.
B. caapi's alkaloid profile works as a system. tetrahydroharmine (THH) adds [[substance_class:pharmacological/serotonin-reuptake-inhibitor]] through an SSRI-like mechanism{{cite|doi=10.3390/biom12111618|anchor=0702baa3}}. [[substance:harmaline]] contributes weaker MAO-A [[glossary:inhibition]] and has anti-inflammatory properties through several pathways{{cite|doi=10.1007/s00210-025-04220-w|anchor=e43966dd}}{{cite|doi=10.3390/biom12111618|anchor=72be3072}}. Harmine also activates serotonin [[glossary:receptor|receptors]] at higher concentrations and increases [[glossary:dopamine]] release in brain [[glossary:reward]] areas through a separate pathway{{cite|doi=10.1177/0269881112463125|anchor=f98e75c9}}.
Alkaloid concentrations vary enormously across batches — relative standard deviations of 78.9–170% have been documented{{cite|doi=10.3390/plants9070870|anchor=840337f7}}. Cultivar, growing conditions, stem age, and harvest timing all affect concentration. A dose calibrated on one batch may deliver substantially different alkaloid quantities from the next.
[[substance:harmine]] is the dominant alkaloid in B. caapi, present at a mean concentration of 4.79 mg/g dried liana{{cite|doi=10.3390/plants9070870|anchor=7b15d968}}. It functions as a potent reversible [[glossary:mao-a]] [[glossary:inhibitor]] at low nanomolar concentrations{{cite|doi=10.1093/toxsci/kfaf118|anchor=d601c247}}. In [[substance:ayahuasca]] preparations, this MAO-A [[glossary:inhibition]] prevents gastrointestinal and hepatic deamination of [[substance:dmt]] contributed by the admixture plant, enabling oral [[glossary:bioavailability]] of an otherwise orally inactive [[substance_class:chemical/tryptamine]]{{cite|pubmed=12660312|anchor=9397d9d9}}.
The B. caapi alkaloid profile operates as a functional system rather than a single-compound action. Harmine provides the primary MAO-A [[glossary:blockade]]; tetrahydroharmine (THH) contributes secondary [[substance_class:pharmacological/serotonin-reuptake-inhibitor]] with an SSRI-like mechanism; and [[substance:harmaline]] adds weaker MAO-A inhibition{{cite|doi=10.3390/biom12111618|anchor=71046fe6}}. This three-alkaloid combination produces a layered pharmacological effect — harmine and harmaline block the [[glossary:enzyme]] that would destroy orally [[glossary:ingestion|ingested]] DMT, while THH modulates mood through an independent serotonergic pathway.
Beyond the MAO-A axis, harmine acts as a [[glossary:5-ht2a]] [[glossary:agonist|receptor agonist]] at higher concentrations and augments [[glossary:efflux|dopamine efflux]] in the [[glossary:nucleus-accumbens]] via a presynaptic 5-HT₂A-dependent mechanism that is independent of its MAOI activity{{cite|doi=10.1177/0269881112463125|anchor=e2cddc88}}. Harmaline exhibits anti-inflammatory activity through COX inhibition, nitric oxide pathway suppression, and Nrf-2/[[substance_class:pharmacological/antioxidant]] signalling [[glossary:activation]]{{cite|doi=10.1007/s00210-025-04220-w|anchor=f53cbe07}}. Harmine is also a potent inhibitor of DYRK1A, a kinase of potential relevance to neurodevelopmental and neurodegenerative disease research{{flag|citation-needed}}.
Alkaloid concentrations in B. caapi are extremely variable. Relative standard deviations of 78.9–170% across batches have been documented{{cite|doi=10.3390/plants9070870|anchor=4d7bae36}}, meaning a dose calibrated from one batch may deliver substantially different alkaloid quantities from another. Cultivar, growing conditions, harvest timing, and stem age all influence concentration. This variability is the primary practical challenge for dosing accuracy with any B. caapi preparation.
===Primary β-carboline alkaloids===
B. caapi contains three primary psychoactive β-carboline alkaloids, all sharing a pyrido[3,4-b][[substance_class:chemical/indole]] core structure and differing in their degree of ring saturation:
* '''Harmine''' (7-methoxy-1-methyl-9H-pyrido[3,4-b]indole; C₁₃H₁₂N₂O; MW 212.25 g/mol) — the dominant alkaloid; fully aromatic β-carboline
* '''Harmaline''' (7-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indole; C₁₃H₁₄N₂O; MW 214.26 g/mol) — dihydro-β-carboline
* '''Tetrahydroharmine''' (THH; (1R)-7-methoxy-1-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole; C₁₃H₁₆N₂O; MW 216.28 g/mol) — tetrahydro-β-carboline
===Quantified concentrations===
The largest quantification study to date analyzed 159 B. caapi liana samples and 33 [[substance:ayahuasca]] preparations from multiple Brazilian regions via LC-MS/MS{{cite|doi=10.3390/plants9070870|anchor=01f103fc}}:
====Dried B. caapi liana====
RSD values of 78.9–170% represent extreme variability across samples — a structural challenge for standardization and consistent dosing in any preparation derived from this [[glossary:plant-material]].
====Ayahuasca brew====
Measured across 33 traditional preparations and validated in an independent 38-sample Brazilian [[glossary:cohort]]{{cite|doi=10.3390/plants9070870|anchor=d9f344fc}}{{cite|doi=10.1016/j.jchromb.2019.06.014|anchor=39c4ef34}}:
Validated [[glossary:analytical-method|analytical methods]] for these alkaloids include GC{{cite|doi=10.1002/pca.1110|anchor=1799eedd}}, HPLC with limit-of-quantification values of 0.3–1.0 ng/mL in [[glossary:plasma]]{{cite|pubmed=12361741|anchor=bc2f6300}}, and LC-MS/MS{{cite|doi=10.1016/j.jchromb.2019.06.014|anchor=39eb95fb}}. Wang and colleagues confirmed the dominant constituents and characterized their [[glossary:monoamine-oxidase]]-inhibitory and antioxidative activities{{cite|doi=10.1016/j.jep.2010.02.013|anchor=83772f4f}}.
===Chemotype and cultivar variation===
Native (wild-harvested) B. caapi demonstrates significantly higher [[substance:harmine]] concentrations than cultivated material{{cite|doi=10.3390/plants9070870|anchor=8a39ff24}}. Regional variation is also documented: samples from the Federal District/Goiás region of Brazil showed higher THH content than samples from the state of Acre. This geographic and cultivation-status variation has direct implications for the pharmacological [[glossary:potency]] of any preparation derived from different source material.
===Preparation-dependent alkaloid changes===
Extended boiling during traditional ayahuasca preparation reduces harmine to [[substance:harmaline]] and further to tetrahydroharmine via progressive ring reduction{{cite|doi=10.3390/plants9070870|anchor=be0c7d9a}}. Ayahuasca brews therefore show proportionally less harmine and more THH relative to raw plant material — a chemically predictable shift that alters the balance of [[glossary:mao-a]] [[glossary:inhibition]] (harmine-dominated) versus [[substance_class:pharmacological/serotonin-reuptake-inhibitor]] (THH-dominated) in the final preparation.
===Minor alkaloids===
B. caapi extracts yield additional compounds beyond the three primary β-carbolines. HPLC-DAD and high-resolution LC-MS/MS isolation identified five bioactive fractions with masses consistent with alkaloid [[glossary:derivative|derivatives]] (exact [M+H]⁺ masses: 174.09, 233.13, 353.17, 304.30, 188.11, 205.08){{cite|doi=10.3390/molecules27082500|anchor=307d5554}}. Harmol and harmalol — O-demethylation [[glossary:metabolite|metabolites]] of harmine and harmaline respectively — have been identified in human plasma after ayahuasca [[glossary:ingestion]]{{cite|pubmed=12361741|anchor=e79fef6f}}. The [[glossary:in-vivo|in vivo]] pharmacological significance of these minor alkaloids remains limited to preliminary [[glossary:in-vitro|in vitro]] characterization.
| Alkaloid | Mean (mg/g) | RSD (%) |
|---|---|---|
| Harmine | 4.79 | 170 |
| Harmaline | 0.451 | 107 |
| Tetrahydroharmine | 2.18 | 78.9 |
| Compound | Range (mg/mL) |
|---|---|
| Harmine | 0.109–7.11 |
| Harmaline | 0.012–0.945 |
| Tetrahydroharmine | 0.09–3.05 |
| DMT (from admixture plant) | 0.10–3.12 |
===Where it acts===
B. caapi's β-carbolines target the [[glossary:monoamine-oxidase]] system. [[substance:harmine]]'s reversible [[glossary:mao-a]] [[glossary:inhibition]] raises [[glossary:serotonin|synaptic serotonin]], [[glossary:norepinephrine]], and [[glossary:dopamine]] by preventing their enzymatic breakdown{{cite|doi=10.1093/toxsci/kfaf118|anchor=1b2bc29c}}{{cite|doi=10.3390/biom12111618|anchor=d84bb8a1}}. In full [[substance:ayahuasca]], this peripheral MAO-A [[glossary:blockade]] enables [[substance:dmt]] to survive [[glossary:first-pass-metabolism]] and reach the brain, where it activates [[glossary:5-ht2a]] [[glossary:receptor|receptors]] across the [[glossary:cortex]]{{cite|pubmed=12660312|anchor=c7d3f743}}. THH adds a second serotonergic layer through SSRI-like [[glossary:reuptake-inhibitor]]{{cite|doi=10.3390/biom12111618|anchor=fbd4276f}}.
===What it changes===
Functional MRI studies show that ayahuasca decreases [[glossary:default-mode-network]] (DMN) activity — including the posterior cingulate cortex and medial [[glossary:prefrontal-cortex]] — with reduced connectivity within the precuneus{{cite|doi=10.1371/journal.pone.0118143|anchor=a0205ba3}}. Broader neuroimaging review confirms acute excitation of frontolateral cortex, medial temporal lobe, and occipital cortex alongside this DMN suppression{{cite|doi=10.1016/j.neubiorev.2016.10.026|anchor=c47323f7}}, a pattern that may underlie the dissolution of habitual [[glossary:self-referential-thought]] and vivid internal imagery.
B. caapi alkaloids (harmine, THH, [[substance:harmaline]], and the harmine [[glossary:metabolite]] harmol) stimulate adult [[glossary:neurogenesis]] [[glossary:in-vitro|in vitro]] — promoting neural stem cell proliferation, migration, and differentiation{{cite|doi=10.1038/s41598-017-05407-9|anchor=044a92e7}}. Post-acute enhancements in mindfulness capacity and persistent DMN [[glossary:modification|modifications]] have been documented at 24 hours after administration{{cite|doi=10.1093/ijnp/pyx036|anchor=68c6e2e4}}.
{{DiscoverMore|Open Questions}}
* No pharmacokinetic data exist for B. caapi-only preparations — all published human data derive from ayahuasca or standardized DMT+harmine formulations.
* The clinical significance of harmine's [[glossary:cyp2d6]] and [[glossary:cyp3a4]] inhibition relative to its MAO-A inhibition remains uncharacterized.
* Whether the neurogenesis observed in vitro translates to clinically relevant structural [[glossary:neuroplasticity]] in humans has not been established.
{{/DiscoverMore}}
===Where it acts===
B. caapi's β-carbolines target the brain's [[substance_class:pharmacological/monoamine-system]]. [[substance:harmine]] blocks the [[glossary:enzyme]] that breaks down [[glossary:serotonin]], [[glossary:norepinephrine]], and [[glossary:dopamine]] — raising all three{{cite|doi=10.1093/toxsci/kfaf118|anchor=b61a5fdb}}{{cite|doi=10.3390/biom12111618|anchor=d4fab46f}}. In full [[substance:ayahuasca]], this enables [[substance:dmt]] to reach the brain and activate serotonin [[glossary:receptor|receptors]] across the [[glossary:cortex]]{{cite|pubmed=12660312|anchor=d9ec8228}}, while THH independently adds a second serotonergic effect{{cite|doi=10.3390/biom12111618|anchor=81d83a6b}}.
===What it changes===
Brain imaging shows ayahuasca quiets the [[glossary:default-mode-network]] — the brain's background activity tied to [[glossary:self-referential-thought]] — with reduced connectivity in key regions{{cite|doi=10.1371/journal.pone.0118143|anchor=1006ffe2}}{{cite|doi=10.1016/j.neubiorev.2016.10.026|anchor=66b06ac2}}. This likely underlies the dissolution of habitual thinking and the vivid internal imagery. B. caapi alkaloids stimulate new neural growth in lab studies{{cite|doi=10.1038/s41598-017-05407-9|anchor=a595ac90}}, and [[effect:mindfulness-enhancement]] capacity has been measured 24 hours after administration{{cite|doi=10.1093/ijnp/pyx036|anchor=ba9dc16f}}.
{{DiscoverMore|Open Questions}}
* No pharmacokinetic data exist for B. caapi-only preparations — all published human data derive from ayahuasca or standardized DMT+harmine formulations.
* The clinical significance of harmine's [[glossary:cyp2d6]] and [[glossary:cyp3a4]] [[glossary:inhibition]] relative to its [[glossary:mao-a]] inhibition remains uncharacterised.
* Whether the [[glossary:neurogenesis]] observed [[glossary:in-vitro|in vitro]] translates to clinically relevant structural [[glossary:neuroplasticity]] in humans has not been established.
{{/DiscoverMore}}
The experiential character of B. caapi preparations depends fundamentally on whether [[substance:dmt]]-containing admixture plants are present. Classic [[substance:ayahuasca]] — B. caapi combined with ''Psychotria viridis'' — produces a dense, multi-layered state integrating intense visual and auditory perceptual shifts, [[effect:emotional-enhancement]], introspective depth, and prominent gastrointestinal [[glossary:activation]]. B. caapi alone reportedly produces primarily somatic and introspective effects without intense visual [[glossary:hallucination]], though no controlled clinical data exist for this preparation. Set, setting, and ceremonial container exert unusually strong influence on experience quality; batch-to-batch alkaloid variability (RSD 78.9–170%) further ensures that no two sessions are pharmacologically identical{{cite|doi=10.3390/plants9070870|anchor=6a673efa}}.
Ayahuasca occupies a distinct position among [[glossary:serotonergic-psychedelics]]. Where psilocybin or [[substance:lsd]] acts primarily through direct [[glossary:5-ht2a]] agonism, ayahuasca's pharmacology is a multi-compound interaction — reversible [[glossary:mao-a]] [[glossary:inhibition]] enabling oral DMT activity, layered with THH's [[substance_class:pharmacological/serotonin-reuptake-inhibitor]]. This mechanistic complexity, combined with the pronounced [[effect:nausea]] and purging, distinguishes it from all [[glossary:synthetic]] [[substance_class:chemical/tryptamine]] and [[substance_class:chemical/lysergamide]] experiences.
===Classic ayahuasca (B. caapi + ''Psychotria viridis'' — oral decoction)===
The archetypal preparation combines pounded or mashed B. caapi vine stalks with leaves of ''Psychotria viridis'' (or other [[substance:dmt]]-containing admixture plants) in water, boiled for 8–12+ hours and concentrated by continued evaporation. The resulting decoction is an opaque, dark-brown liquid with a characteristically bitter taste.
'''Dose:''' In controlled research settings, standardized [[substance:ayahuasca]] has been administered at '''0.6–0.85 mg DMT/kg body weight''' (encapsulated freeze-dried material){{cite|pubmed=12660312|anchor=95ffdc79}}. Traditional ceremonial servings are typically 50–100 mL of liquid, but [[glossary:potency]] varies enormously — measured [[substance:harmine]] concentrations range from 0.109 to 7.11 mg/mL, and DMT from 0.10 to 3.12 mg/mL, across Brazilian samples{{cite|doi=10.1016/j.jchromb.2019.06.014|anchor=5b0f0d13}}{{cite|doi=10.3390/plants9070870|anchor=749f7468}}. Traditional healers calibrate dose empirically based on experience and participant characteristics; standardized mg/kg dosing is not feasible outside research contexts.
* '''Onset:''' 20–60 min
* '''Peak:''' 1.5–2 h
* '''Total duration:''' 4–6 h{{cite|pubmed=12660312|anchor=e6f9009c}}
'''Effect character:''' Intense visual and auditory perceptual [[glossary:modification]], cognitive and emotional intensification, [[glossary:introspection]], and pronounced gastrointestinal effects ([[effect:nausea]] and [[effect:vomiting]] are commonly reported and are culturally contextualized as "purge" in ceremonial settings). Mild cardiovascular effects include diastolic [[glossary:blood-pressure]] increase (~9 mmHg at higher doses) and mild [[effect:pupil-dilation]]{{cite|pubmed=12660312|anchor=abbf3530}}{{cite|doi=10.1097/JCP.0b013e31823607f6|anchor=9faf3c68}}. Transient neuroendocrine effects include prolactin and cortisol [[glossary:elevation]], and transient immunological shifts (NK cell increase, CD4 and CD3 decrease returning to baseline within 24 hours){{cite|doi=10.1097/JCP.0b013e31823607f6|anchor=e226a14f}}.
Potency variability is extreme: alkaloid content shows RSD of 78.9–170% across batches{{cite|doi=10.3390/plants9070870|anchor=b78570b3}}. A dose calibrated on one batch may deliver substantially different alkaloid quantities from another. See the Dose by preparation card for structured reference.
===B. caapi alone (oral decoction)===
B. caapi-only preparations — sometimes called "caapi solo" — involve boiling B. caapi vine without DMT-containing admixture plants. This preparation is documented among some indigenous groups and is described in traditional-use accounts as producing primarily somatic and introspective effects without the intense visual [[glossary:hallucination|hallucinations]] attributed to DMT{{cite|doi=10.2174/1570159x16666180125095902|anchor=e57a9595}}{{cite|doi=10.3389/fphar.2016.00035|anchor=3f580cda}}.
'''No published dose, onset, duration, or pharmacokinetic data exist for B. caapi-only preparations.''' All published quantitative parameters derive from ayahuasca (B. caapi combined with DMT admixture) or standardized harmine formulations. Traditional-use accounts are the sole evidence source for this preparation's effect character{{flag|safety-citation-needed}}.
===Buccal DMT+harmine formulation (investigational)===
A [[glossary:pharmaceutical-grade|pharmaceutical-grade]] buccal formulation combining DMT (0–120 mg) with harmine (0–180 mg) has been evaluated in a factorial dose-escalation study{{cite|doi=10.1016/j.biopha.2025.117908|anchor=2e9765c0}}. This preparation produces [[index:effects|subjective effects]] lasting 4–5 h, with peak DMT cmax of 33 ng/mL and harmine cmax of 49 ng/mL. [[glossary:tmax]] increases with [[glossary:dose-escalation]] for both compounds. This formulation is investigational and not commercially available.
The character of B. caapi preparations depends almost entirely on whether a [[substance:dmt]]-containing admixture plant is present. Classic [[substance:ayahuasca]] — brewed with ''Psychotria viridis'' — produces intense visual and auditory changes, [[effect:emotional-enhancement]], deep [[glossary:introspection]], and strong [[effect:nausea]]. B. caapi alone produces mainly somatic and mildly introspective effects without intense [[glossary:hallucination]], though no controlled data exist for this preparation. Set, setting, and ceremonial context shape the experience significantly; batch-to-batch alkaloid variation ensures no two sessions are pharmacologically identical{{cite|doi=10.3390/plants9070870|anchor=ff1b3d12}}.
Ayahuasca occupies a distinct place among [[glossary:serotonergic-psychedelics]]. Psilocybin and [[substance:lsd]] act mainly through direct [[glossary:serotonin]] [[glossary:receptor-activation]]; ayahuasca's effects arise from a more complex interaction — [[substance:harmine]] and [[substance:harmaline]] block the [[glossary:enzyme]] that would destroy DMT, while THH independently modulates serotonin. The result is a longer, more somatic, and more emotionally confrontational experience than typical [[glossary:synthetic]] [[substance_class:psychoactive/psychedelic|psychedelics]], shaped by multi-compound chemistry rather than a single active molecule.
====Traditional ayahuasca decoction====
'''Traditional ayahuasca''' is prepared by extended boiling (typically 8–12+ hours) of pounded or shredded B. caapi stems and bark, combined with leaves of ''Psychotria viridis'' or other [[substance:dmt]]-containing admixture plants{{cite|doi=10.2174/1570159x16666180125095902|anchor=b86120c7}}{{cite|doi=10.3389/fphar.2016.00035|anchor=bf2129bd}}. The resulting brew varies widely in alkaloid concentration depending on [[glossary:plant-material]] quantity, boiling duration, and water volume. Onset occurs within 30–60 minutes; effects peak at approximately 1.5–2 hours and resolve within 4–6 hours{{cite|pubmed=12660312|anchor=e3c551f5}}. [[effect:nausea]] and [[effect:vomiting]] are expected and occur in a majority of users. Traditional preparations are dose-calibrated by experienced practitioners (''curanderos'' or ''vegetalistas''), not by standardized measurement.
====B. caapi-only decoction====
'''B. caapi-only''' decoctions, prepared without DMT-containing admixture, are documented among some indigenous groups. These preparations produce primarily somatic and mild introspective effects without the intense visual [[glossary:hallucination|hallucinations]] characteristic of full [[substance:ayahuasca]]. No published pharmacokinetic data or controlled dose-ranging studies exist for this preparation form; dosing relies entirely on traditional practitioner judgment.
====Standardized research formulations====
'''Encapsulated ayahuasca''' at standardized doses (0.6–0.85 mg DMT/kg body weight) has been used in controlled clinical trials{{cite|pubmed=12660312|anchor=9e663fd9}}. '''Buccal DMT+harmine''' formulations (DMT 0–120 mg, [[substance:harmine]] 0–180 mg) have also been studied, producing comparable effect timelines of 4–5 hours with more consistent alkaloid delivery than traditional decoctions{{cite|doi=10.1016/j.biopha.2025.117908|anchor=86957f1f}}. Buccal administration produced peak DMT cmax of 33 ng/mL and harmine cmax of 49 ng/mL{{cite|doi=10.1016/j.biopha.2025.117908|anchor=5632ca40}}.
====Commercial vine products====
'''Commercial B. caapi products''' — dried shredded vine, vine extract, and pre-prepared brew concentrates — are sold through online botanical retailers. No standardization framework, Certificate of Analysis requirement, or accredited testing program exists for these products{{cite|doi=10.3390/jcm11041147|anchor=7bd59002}}{{cite|doi=10.1016/j.jchromb.2019.06.014|anchor=b3f887f0}}. Alkaloid content is variable and typically unlabelled. Batch-to-batch variability (RSD 78.9–170%) means a dose calibrated on one product may deliver substantially different alkaloid quantities from another{{cite|doi=10.3390/plants9070870|anchor=2cb557ec}}.
Per-preparation dose tiers, timelines, and [[glossary:bioavailability]] data are in the Dose · by preparation card on this page.
====Traditional ayahuasca decoction====
'''Traditional ayahuasca''' is prepared by boiling pounded or shredded B. caapi stems with leaves of ''Psychotria viridis'' or another [[substance:dmt]]-containing plant for 8–12 hours or more{{cite|doi=10.2174/1570159x16666180125095902|anchor=6e52fe91}}{{cite|doi=10.3389/fphar.2016.00035|anchor=3dc3469b}}. Alkaloid concentration varies widely depending on plant quantity, boiling time, and water volume.
* '''Onset:''' 30–60 minutes
* '''Peak:''' approximately 1.5–2 hours
* '''Duration:''' 4–6 hours{{cite|pubmed=12660312|anchor=4246b501}}
* [[effect:nausea]] and [[effect:vomiting]] are expected; they occur in most users
* Dose is calibrated by the practitioner (''curandero'' or ''vegetalista''), not by standardized measurement
====B. caapi-only decoction====
'''B. caapi-only''' decoctions — without a DMT admixture plant — produce primarily somatic and mildly introspective effects, without intense visual [[glossary:hallucination]]. No pharmacokinetic or controlled dose-ranging data exist for this preparation; dosing relies entirely on traditional practitioner judgment.
====Standardized research formulations====
'''Encapsulated ayahuasca''' at 0.6–0.85 mg DMT/kg body weight has been used in controlled clinical trials{{cite|pubmed=12660312|anchor=eb29c947}}. '''Buccal DMT+harmine''' formulations (DMT 0–120 mg, [[substance:harmine]] 0–180 mg) produce comparable effects over 4–5 hours with more consistent alkaloid delivery than traditional brews{{cite|doi=10.1016/j.biopha.2025.117908|anchor=6bb01693}}. [[glossary:peak]] levels measured with buccal administration: DMT 33 ng/mL, harmine 49 ng/mL{{cite|doi=10.1016/j.biopha.2025.117908|anchor=cb24c13f}}.
====Commercial vine products====
'''Commercial B. caapi''' — dried vine, extract, or pre-prepared concentrate — is sold through online retailers. No Certificate of Analysis requirement, standardization framework, or accredited testing program exists for these products{{cite|doi=10.3390/jcm11041147|anchor=cf193c67}}{{cite|doi=10.1016/j.jchromb.2019.06.014|anchor=0aecd097}}. Alkaloid content is variable and typically unlabelled. Batch-to-batch variation of 78.9–170% means a dose calibrated on one batch may deliver very different alkaloid quantities from the next{{cite|doi=10.3390/plants9070870|anchor=5d73dbc9}}.
====Toxicity====
No death has been attributed to [[substance:ayahuasca]] alone in toxicological autopsy{{cite|doi=10.3390/jcm11041147|anchor=42080c47}}, and cell-level harm appears only at concentrations far above typical use{{cite|doi=10.3390/molecules27082500|anchor=46471426}}{{cite|pubmed=8889686|anchor=e825435b}}. [[effect:nausea]] and [[effect:vomiting]] occur in most users{{cite|doi=10.1590/1516-4446-2020-0913|anchor=52d0c05d}}. Higher doses raise diastolic [[glossary:blood-pressure]] by approximately 9 mmHg, dilate pupils, and elevate cortisol{{cite|pubmed=12660312|anchor=4508629d}}{{cite|doi=10.1097/JCP.0b013e31823607f6|anchor=b8dbb5fb}}. Long-term users consuming ayahuasca at least twice monthly show no liver [[glossary:enzyme]] changes{{cite|doi=10.1080/02791072.2018.1557355|anchor=0a73a4ac}}. Commercial preparations have no standardization framework or Certificate of Analysis requirement{{cite|doi=10.3390/jcm11041147|anchor=af22a071}}{{cite|doi=10.1016/j.jchromb.2019.06.014|anchor=77eae578}}; [[glossary:contamination]] by pesticides or heavy metals has not been systematically studied{{flag|safety-citation-needed}}.
====Psychological Risks====
Acute [[effect:anxiety]], [[effect:confusion]], and panic are common even at standard doses{{cite|pubmed=16149336|anchor=089ba823}}. A survey of 614 religious users found gastrointestinal symptoms were most frequent; a minority reported lasting [[glossary:adverse-effects]]{{cite|doi=10.1590/1516-4446-2020-0913|anchor=843f7d0a}}. Risk is elevated for people with personal or family history of [[glossary:psychosis]], bipolar [[glossary:disorder]] type I, or severe psychiatric illness{{cite|doi=10.1016/j.tmaid.2021.102206|anchor=48ed8f6b}}{{cite|doi=10.2174/1570159x16666180125095902|anchor=61547250}}. Non-ceremonial settings without experienced facilitation carry elevated risk of psychological crisis{{cite|doi=10.1016/j.tmaid.2021.102206|anchor=9206df0e}}.
====Tolerance & Dependence====
No [[glossary:physical-dependence]] or [[glossary:withdrawal]] has been documented for B. caapi or ayahuasca{{cite|doi=10.2174/1570159x16666180125095902|anchor=e5cecc9e}}{{cite|doi=10.1371/journal.pone.0042421|anchor=28e2a8c2}}. Long-term ritual users show no [[effect:cognitive-impairment]]{{cite|doi=10.1371/journal.pone.0042421|anchor=f31e94b6}}, and enhanced working memory has been confirmed in long-term users{{cite|doi=10.1007/s00406-024-01817-9|anchor=52f91920}}. First-time users assessed at 1 and 6 months after initial use showed improvements in mental health measures{{cite|doi=10.1038/s41598-020-61169-x|anchor=9342e757}}. [[substance:dmt]] [[glossary:tolerance]] develops with repeated acute dosing; tolerance to [[substance:harmine]]'s [[glossary:mao-a]] [[glossary:inhibition]] has not been systematically studied.
====Drug Interactions====
The dominant risk involves serotonergic [[glossary:medication|medications]]. Harmine and [[substance:harmaline]] block MAO-A — the enzyme that normally clears [[glossary:serotonin]] from synapses. Combining this with SSRIs, SNRIs, triptans, [[substance:tramadol]], or [[substance:dextromethorphan]] raises serotonin to dangerous levels, producing '''serotonin syndrome''' — [[glossary:hyperthermia]], [[glossary:agitation]], [[glossary:muscle-rigidity]], and [[glossary:seizure|seizures]]{{cite|doi=10.3390/biom12111618|anchor=4a146d8c}}{{cite|doi=10.1093/toxsci/kfaf118|anchor=b6b8c8ce}}.
Tyramine-rich foods (aged cheese, cured meats) are normally broken down by the same enzyme; its inhibition could in principle raise blood pressure, though no hypertensive crises were recorded among 614 religious users{{cite|doi=10.1590/1516-4446-2020-0913|anchor=054bac72}}. The risk appears lower with reversible MAO-A inhibition than with pharmaceutical MAOIs{{flag|safety-citation-needed}}.
[[substance:amphetamine|Amphetamines]] and [[substance:cocaine]] may produce amplified effects through reduced MAO-A catabolism{{flag|safety-citation-needed}}. Harmine inhibits [[glossary:liver-enzymes]] that metabolize certain [[substance_class:psychoactive/antipsychotic|antipsychotics]], [[substance_class:psychoactive/antidepressant|antidepressants]], and [[substance_class:psychoactive/opioid|opioids]] — potentially raising their blood levels{{flag|safety-citation-needed}}. Anecdotal reports suggest [[substance:lithium]] combined with [[substance_class:psychoactive/psychedelic|psychedelics]] may carry seizure and cardiac risk{{flag|safety-citation-needed}}.
====Contraindications====
'''''Absolute:'''''
* '''Personal history of psychotic disorders or bipolar disorder type I:''' elevated risk of psychosis precipitation and acute adverse reactions{{cite|doi=10.1016/j.tmaid.2021.102206|anchor=66654391}}{{cite|doi=10.2174/1570159x16666180125095902|anchor=616fd64b}}
* '''Concurrent serotonergic medication''' (SSRIs, SNRIs, triptans, tramadol, dextromethorphan): mechanistic risk of [[glossary:serotonin-syndrome]] via MAO-A inhibition{{cite|doi=10.3390/biom12111618|anchor=647a18ab}}
'''''Relative:'''''
* '''Severe cardiovascular disease:''' diastolic blood pressure increase (~9 mmHg) and [[glossary:sympathomimetic|sympathomimetic effects]] documented at standard doses{{cite|pubmed=12660312|anchor=ff08c025}}
* '''Family history of psychotic disorders:''' elevated [[glossary:psychological-risk]]{{cite|doi=10.2174/1570159x16666180125095902|anchor=937c2e65}}
* '''Concurrent lithium use:''' anecdotal reports of seizure and cardiac risk in the broader psychedelic literature{{flag|safety-citation-needed}}
* '''Pregnancy:''' no reproductive safety data exist; MAO-A inhibition and serotonergic [[glossary:modulation]] present theoretical fetal risk{{flag|safety-citation-needed}}
* '''Hepatic impairment:''' risk of altered harmine [[glossary:metabolism]] and prolonged MAO-A inhibitory effect{{flag|safety-citation-needed}}
'''''Detection:'''''
Harmala alkaloids (harmine, harmaline, THH) are more reliable [[glossary:biomarker|biomarkers]] than DMT for identifying ayahuasca exposure in forensic urine screens, as DMT clears quickly from [[glossary:plasma]]{{cite|doi=10.1093/jat/bky105|anchor=0fa86bfd}}. Hair analysis can detect all four alkaloids at very low concentrations{{cite|doi=10.1016/j.talanta.2026.129455|anchor=3abbc9a2}}.
====Toxicity====
No published human [[glossary:lethal-dose|LD50]] data exist for B. caapi or [[substance:ayahuasca]]. A [[glossary:systematic-review]] found no case in which autopsy and toxicological examination together attributed death to ayahuasca alone{{cite|doi=10.3390/jcm11041147|anchor=a509aed4}}. [[glossary:in-vitro]] cytotoxicity appeared only at [[substance:harmine]] concentrations far exceeding therapeutic [[glossary:plasma-concentration|plasma levels]]{{cite|doi=10.3390/molecules27082500|anchor=18d5dd83}}{{cite|pubmed=8889686|anchor=6c3d4e70}}.
The most frequently reported acute physiological effect is '''nausea and vomiting''', occurring in a majority of users{{cite|doi=10.1590/1516-4446-2020-0913|anchor=0ee4a189}}. At higher doses, a diastolic [[glossary:blood-pressure]] increase of approximately 9 mmHg has been observed, along with mild [[glossary:sympathomimetic|sympathomimetic effects]] including [[effect:pupil-dilation]], prolactin [[glossary:elevation]], and cortisol elevation{{cite|pubmed=12660312|anchor=2a711647}}{{cite|doi=10.1097/JCP.0b013e31823607f6|anchor=524a12d4}}. Transient lymphocyte [[glossary:modulation]] (NK cell increase, CD4 and CD3 decrease) has been documented, returning to baseline within 24 hours{{cite|doi=10.1097/JCP.0b013e31823607f6|anchor=64a6036f}}.
No significant alteration in liver function tests was found in chronic users consuming ayahuasca twice monthly for at least one year{{cite|doi=10.1080/02791072.2018.1557355|anchor=16276a65}}.
No systematic studies on pesticide [[glossary:contamination]], heavy metal content (lead, cadmium, arsenic, mercury), or mycotoxin contamination in commercial B. caapi preparations have been published{{flag|safety-citation-needed}}. No standardization framework, Certificate of Analysis requirement, or ISO/IEC-accredited testing program exists for commercial products{{cite|doi=10.3390/jcm11041147|anchor=6cda40d3}}{{cite|doi=10.1016/j.jchromb.2019.06.014|anchor=1b402d16}}. Commercially sold preparations may contain variable and unlabelled amounts of active alkaloids. This constitutes a practical safety gap, particularly for non-ceremonial use where experienced dose calibration by a traditional practitioner is absent.
====Psychological Risks====
Acute [[effect:anxiety]], transient [[effect:confusion]], and panic reactions are commonly reported even at standard ayahuasca doses{{cite|pubmed=16149336|anchor=bb056139}}. In a cross-sectional study of 614 religious users, the most frequent [[glossary:adverse-effects]] were transient gastrointestinal symptoms; a minority reported being "very negatively affected" by persistent adverse effects{{cite|doi=10.1590/1516-4446-2020-0913|anchor=f41223e3}}. Adverse effects were more frequent in participants with pre-existing psychiatric diagnoses, although psychiatric [[glossary:medication]] use was not statistically associated with increased adverse effect frequency in this sample{{cite|doi=10.1590/1516-4446-2020-0913|anchor=db434c80}}.
Risk of acute psychological crisis is elevated in individuals with personal or family history of psychotic [[glossary:disorder|disorders]], bipolar disorder type I, or severe psychiatric illness{{cite|doi=10.1016/j.tmaid.2021.102206|anchor=f4cdf5b6}}{{cite|doi=10.2174/1570159x16666180125095902|anchor=6f0357f5}}. A scoping review identified psychological adverse reactions as the primary documented concern for travellers using ayahuasca in non-ceremonial settings{{cite|doi=10.1016/j.tmaid.2021.102206|anchor=ee0654c5}}.
====Tolerance & Dependence====
No physical dependence or [[glossary:withdrawal]] has been documented for B. caapi or ayahuasca{{cite|doi=10.2174/1570159x16666180125095902|anchor=00fcae79}}{{cite|doi=10.1371/journal.pone.0042421|anchor=7cb0315a}}. Long-term ritual users consuming ayahuasca at least twice monthly show no [[effect:cognitive-impairment]] and no addiction-related problems{{cite|doi=10.1371/journal.pone.0042421|anchor=d6cc267a}}. Preserved or improved cognitive function — including enhanced working memory — has been confirmed in long-term users compared with beginners{{cite|doi=10.1007/s00406-024-01817-9|anchor=8bac44d1}}.
Naive users assessed at 1 and 6 months after first use showed improvements in mental health measures{{cite|doi=10.1038/s41598-020-61169-x|anchor=17b7a411}}. [[glossary:tolerance]] to [[substance:dmt]]'s [[substance_class:psychoactive/psychedelic]] effects develops with repeated acute dosing; tolerance to MAO-A [[glossary:inhibition]] by harmine has not been systematically studied.
====Drug Interactions====
B. caapi's harmine and [[substance:harmaline]] are reversible MAO-A [[glossary:inhibitor|inhibitors]]. This mechanism creates the primary herb-[[glossary:drug-interaction]] risk.
'''Serotonergic agents:''' MAO-A inhibition combined with [[substance_class:pharmacological/serotonin-reuptake-inhibitor]] or [[glossary:serotonin-release]] increases [[glossary:serotonin|synaptic serotonin]], creating mechanistic risk for '''serotonin syndrome''' — a potentially life-threatening condition characterised by [[glossary:hyperthermia]], [[glossary:agitation]], clonus, and hyperreflexia. Affected drug classes include SSRIs, SNRIs, triptans, [[substance:tramadol]], meperidine, and [[substance:dextromethorphan]]{{cite|doi=10.3390/biom12111618|anchor=31f14605}}{{cite|doi=10.1093/toxsci/kfaf118|anchor=440ba5b8}}. The interaction [[glossary:severity]] is based on mechanistic [[glossary:inference]] from the MAOI pharmacology class{{flag|safety-citation-needed}}.
'''Tyramine-containing foods:''' MAO-A normally catabolises dietary tyramine; inhibition may produce hypertensive crisis. B. caapi produces reversible (not irreversible) MAO-A inhibition, and no hypertensive crises were documented among 614 religious users{{cite|doi=10.1590/1516-4446-2020-0913|anchor=f56806d8}}. The magnitude of tyramine interaction from reversible MAO-A inhibition versus irreversible pharmaceutical MAOIs remains uncharacterised{{flag|safety-citation-needed}}.
'''Sympathomimetics:''' [[substance:amphetamine|Amphetamines]], [[substance:cocaine]], and other sympathomimetic agents may produce augmented dopaminergic and noradrenergic effects via reduced MAO-A catabolism{{flag|safety-citation-needed}}.
'''CYP2D6 and CYP3A4 substrates:''' Harmine inhibits [[glossary:cyp2d6]] and [[glossary:cyp3a4]] in vitro, potentially elevating plasma levels of co-administered medications including certain [[substance_class:psychoactive/antipsychotic|antipsychotics]], [[substance_class:psychoactive/antidepressant|antidepressants]], and [[substance_class:psychoactive/opioid|opioids]]{{flag|safety-citation-needed}}.
'''Lithium:''' Anecdotal reports in the broader psychedelic literature suggest [[glossary:seizure]] and cardiac risk with [[substance:lithium]] combined with psychedelics{{flag|safety-citation-needed}}.
====Contraindications====
'''''Absolute:'''''
* '''Personal history of psychotic disorders or bipolar disorder type I:''' Elevated risk of [[glossary:psychosis]] precipitation and acute adverse psychological reactions{{cite|doi=10.1016/j.tmaid.2021.102206|anchor=e2bd0fd6}}{{cite|doi=10.2174/1570159x16666180125095902|anchor=a82b8df8}}
* '''Concurrent serotonergic medication''' (SSRIs, SNRIs, triptans, tramadol, dextromethorphan): Mechanistic risk of [[glossary:serotonin-syndrome]] via MAO-A inhibition combined with [[glossary:reuptake|serotonin reuptake]] [[glossary:blockade]] or release{{cite|doi=10.3390/biom12111618|anchor=97a5c6c6}}
'''''Relative:'''''
* '''Severe cardiovascular disease:''' Diastolic blood pressure increase (~9 mmHg) and sympathomimetic [[glossary:activation]] documented at standard doses{{cite|pubmed=12660312|anchor=6df31d9a}}
* '''Family history of psychotic disorders:''' Elevated [[glossary:psychological-risk]] based on clinical risk assessment literature{{cite|doi=10.2174/1570159x16666180125095902|anchor=f6455834}}
* '''Concurrent lithium use:''' Uncharacterised seizure and cardiac risk reported anecdotally in the broader psychedelic literature{{flag|safety-citation-needed}}
* '''Pregnancy:''' No reproductive safety data exist for B. caapi or ayahuasca; MAO-A inhibition and serotonergic modulation present theoretical fetal risk{{flag|safety-citation-needed}}
* '''Hepatic impairment:''' Potential for altered harmine [[glossary:metabolism]] and prolonged MAO-A inhibitory effect{{flag|safety-citation-needed}}
'''''Detection:'''''
Harmala alkaloids (harmine, harmaline, THH) serve as more reliable biomarkers than DMT for identifying ayahuasca exposure in forensic urine screens, due to DMT's short [[glossary:plasma]] [[glossary:half-life]]{{cite|doi=10.1093/jat/bky105|anchor=a6831c01}}. Hair analysis via dispersive liquid-liquid microextraction can detect DMT, harmine, harmaline, and THH at pg/mg concentrations, with β-carbolines detected at higher concentrations than DMT{{cite|doi=10.1016/j.talanta.2026.129455|anchor=a6e52e32}}.
===Forms & Identification===
B. caapi is sold as dried shredded vine, whole vine sections, powdered bark, and pre-prepared liquid concentrates. No Certificate of Analysis requirement or accredited testing program exists for any commercial product. Alkaloid concentrations vary by 78.9–170% across batches{{cite|doi=10.3390/plants9070870|anchor=e8c028a8}} — a mild batch may be followed by a significantly stronger one. Request lab-tested preparations with specified [[substance:harmine]], [[substance:harmaline]], and THH concentrations where available.
===Set & Setting===
[[substance:ayahuasca]] ceremonies are traditionally conducted in controlled environments with experienced facilitators managing both physical and psychological dimensions. The prolonged [[effect:nausea]], vivid perceptual shifts, and emotional [[glossary:intensity]] are strongly shaped by environment and mental state. Non-ceremonial settings without experienced facilitation carry elevated risk of adverse psychological reactions{{cite|doi=10.1016/j.tmaid.2021.102206|anchor=390fd725}}.
{{Guideline}}
===Guidelines===
* Start with a small portion of any new preparation source before committing to a full dose — alkaloid content is unpredictable across batches{{cite|doi=10.3390/plants9070870|anchor=858719a2}}
* Observe a washout period of at least 2 weeks from any serotonergic [[glossary:medication]] (5 weeks for fluoxetine) before using any B. caapi preparation
* Follow traditional dietary precautions (''dieta''): avoid tyramine-rich foods (aged cheese, cured meats, fermented products) for at least 24 hours before and after use
* Do not combine with [[substance:alcohol]], [[substance_class:psychoactive/stimulant|stimulants]], or other psychoactive substances
* Ensure access to water and a comfortable space where nausea and [[effect:vomiting]] can be managed safely
* Have a sober, [[glossary:sitter|trusted companion]] present for the full [[glossary:duration-of-action|duration of effects]]
* Allow 4–6 hours for the experience; do not drive or operate machinery until effects have fully resolved
{{/Guideline}}
{{Emergency}}
===Emergency Response===
====Recognising an emergency====
Red flags requiring immediate medical attention:
* Sustained rigid muscle contractions or [[glossary:tremor]] with high fever (signs of '''serotonin syndrome''')
* Unresponsiveness, [[glossary:seizure]], or [[glossary:loss-of-consciousness]]
* Severe [[glossary:chest-pain]], rapid irregular heartbeat, or difficulty breathing
* Prolonged psychotic episode — the person cannot recognise surroundings, is a danger to themselves or others, or is in severe uncontrollable panic
====Immediate steps====
* 1. Move the person to a calm, safe environment
* 2. If [[glossary:serotonin-syndrome]] is suspected ([[glossary:muscle-rigidity]], [[glossary:hyperthermia]], [[glossary:agitation]]), call emergency services immediately — this is a medical emergency
* 3. Do not physically restrain the person unless they are at immediate risk of [[glossary:self-harm]]
* 4. Keep the person cool if [[glossary:body-temperature]] is elevated; remove excess clothing
* 5. If conscious and oriented, reassure them calmly that the effects are temporary and time-limited
====What to tell the dispatcher====
State that the person consumed ayahuasca (a brew containing [[substance_class:pharmacological/monoamine-oxidase-inhibitor|monoamine oxidase inhibitors]] and possibly [[substance:dmt]]), the approximate time of [[glossary:ingestion]], any medications taken in the preceding weeks, and current symptoms. [[glossary:good-samaritan-law|Good Samaritan laws]] in many jurisdictions protect callers who report drug-related emergencies.
No reversal agent exists for B. caapi alkaloids or DMT. Treatment is supportive.
{{/Emergency}}
{{Aftercare}}
===Aftercare & Integration===
Ayahuasca experiences can be psychologically intense, and residual emotional processing commonly continues for days afterward. Maintain adequate [[glossary:hydration]] and eat bland, easily digestible food following the session. Expect [[glossary:fatigue]] and emotional [[glossary:sensitivity]] for 24–48 hours.
[[glossary:integration]] — processing [[glossary:insight|insights]] and emotional material that arose during the experience — benefits from journaling, conversation with a trusted person, or work with a [[glossary:therapist]] familiar with [[glossary:psychedelic-experience|psychedelic experiences]]. Avoid major decisions or high-stress situations in the days following use. Post-acute enhancements in mindfulness capacity have been documented{{cite|doi=10.1093/ijnp/pyx036|anchor=ae6379d2}}, but challenging emotional content may also resurface and warrant professional support.
{{/Aftercare}}
{{Recovery}}
===Recovery & Support===
B. caapi and ayahuasca do not produce [[glossary:physical-dependence]] or a characterised [[glossary:withdrawal]]{{cite|doi=10.2174/1570159x16666180125095902|anchor=48dfb247}}. However, if use has become compulsive or is interfering with daily functioning, reduce frequency gradually and seek professional support.
* '''SAMHSA National Helpline:''' 1-800-662-4357 (free, confidential, 24/7)
* '''Fireside Project:''' 62-FIRESIDE ([[substance_class:psychoactive/psychedelic]] [[glossary:peer-support]] line)
* '''ICEERS:''' International Center for Ethnobotanical Education, Research and Security — legal and safety resources for ayahuasca users
If persistent psychological [[glossary:disturbance]] follows use — including [[effect:anxiety]], [[effect:depersonalization|depersonalisation]], or mood instability lasting more than two weeks — consult a mental health professional with experience in psychedelic-related concerns.
{{/Recovery}}
===Forms & Identification===
B. caapi is sold as dried shredded vine, whole vine sections, powdered bark, and pre-prepared liquid concentrates. No ISO/IEC-accredited testing program or Certificate of Analysis standard exists for any commercial B. caapi product. Because alkaloid concentrations vary by 78.9–170% RSD across batches{{cite|doi=10.3390/plants9070870|anchor=ca88fe22}}, a product that appeared mild in one batch may be significantly stronger in the next. When purchasing commercial products, request lab-tested preparations with specified [[substance:harmine]], [[substance:harmaline]], and THH concentrations where available. For traditional ceremonial preparations, alkaloid consistency depends entirely on the preparer's experience and the sourcing of vine material.
===Set & Setting===
[[substance:ayahuasca]] ceremonies are traditionally conducted in controlled environments with experienced facilitators who manage both the physical and psychological dimensions of the experience. The intense effects — prolonged [[effect:nausea]], vivid perceptual shifts, and [[effect:emotional-enhancement]] — are strongly modulated by environment and mental state. First-time users should ensure a trusted, sober companion is present throughout. Avoid use during periods of [[glossary:distress|acute psychological distress]], bereavement, or mental health instability. Non-ceremonial settings without experienced facilitation carry elevated risk of psychological adverse reactions{{cite|doi=10.1016/j.tmaid.2021.102206|anchor=ea522e51}}.
{{Guideline}}
===Guidelines===
* Start with a small portion of any new preparation source before committing to a full dose — alkaloid content is unpredictable across batches{{cite|doi=10.3390/plants9070870|anchor=a1d044a3}}
* Observe a washout period of at least 2 weeks from any serotonergic [[glossary:medication]] (5 weeks for fluoxetine) before using any B. caapi preparation
* Follow traditional dietary precautions (''dieta''): avoid tyramine-rich foods (aged cheese, cured meats, fermented products) for at least 24 hours before and after use
* Do not combine with [[substance:alcohol]], [[substance_class:psychoactive/stimulant|stimulants]], or other psychoactive substances
* Ensure access to water and a comfortable space where nausea and [[effect:vomiting]] can be managed safely
* Have a sober, [[glossary:sitter|trusted companion]] present for the full [[glossary:duration-of-action|duration of effects]]
* Allow 4–6 hours for the experience; do not drive or operate machinery until effects have fully resolved
{{/Guideline}}
{{Emergency}}
===Emergency Response===
====Recognising an emergency====
Red flags requiring immediate medical attention:
* Sustained rigid muscle contractions or [[glossary:tremor]] with high fever (signs of '''serotonin syndrome''')
* Unresponsiveness, [[glossary:seizure]], or [[glossary:loss-of-consciousness]]
* Severe [[glossary:chest-pain]], rapid irregular heartbeat, or difficulty breathing
* Prolonged psychotic episode — the person cannot recognise surroundings, is a danger to themselves or others, or is in severe uncontrollable panic
====Immediate steps====
* 1. Move the person to a calm, safe environment
* 2. If [[glossary:serotonin-syndrome]] is suspected ([[glossary:muscle-rigidity]], [[glossary:hyperthermia]], [[glossary:agitation]]), call emergency services immediately — this is a medical emergency
* 3. Do not physically restrain the person unless they are at immediate risk of [[glossary:self-harm]]
* 4. Keep the person cool if [[glossary:body-temperature]] is elevated; remove excess clothing
* 5. If conscious and oriented, reassure them calmly that the effects are temporary and time-limited
====What to tell the dispatcher====
State that the person consumed ayahuasca (a brew containing [[substance_class:pharmacological/monoamine-oxidase-inhibitor|monoamine oxidase inhibitors]] and possibly [[substance:dmt]]), the approximate time of [[glossary:ingestion]], any medications taken in the preceding weeks, and current symptoms. [[glossary:good-samaritan-law|Good Samaritan laws]] in many jurisdictions protect callers who report drug-related emergencies.
No reversal agent exists for B. caapi alkaloids or DMT. Treatment is supportive.
{{/Emergency}}
{{Aftercare}}
===Aftercare & Integration===
Ayahuasca experiences can be psychologically intense, and residual emotional processing commonly continues for days afterward. Maintain adequate [[glossary:hydration]] and eat bland, easily digestible food following the session. Expect [[glossary:fatigue]] and emotional [[glossary:sensitivity]] for 24–48 hours.
[[glossary:integration]] — processing [[glossary:insight|insights]] and emotional material that arose during the experience — benefits from journaling, conversation with a trusted person, or work with a [[glossary:therapist]] familiar with [[glossary:psychedelic-experience|psychedelic experiences]]. Avoid major decisions or high-stress situations in the days following use. Post-acute enhancements in mindfulness capacity have been documented{{cite|doi=10.1093/ijnp/pyx036|anchor=e3f94cbe}}, but challenging emotional content may also resurface and warrant professional support.
{{/Aftercare}}
{{Recovery}}
===Recovery & Support===
B. caapi and ayahuasca do not produce [[glossary:physical-dependence]] or a characterised [[glossary:withdrawal]]{{cite|doi=10.2174/1570159x16666180125095902|anchor=f4d180be}}. However, if use has become compulsive or is interfering with daily functioning, reduce frequency gradually and seek professional support.
* '''SAMHSA National Helpline:''' 1-800-662-4357 (free, confidential, 24/7)
* '''Fireside Project:''' 62-FIRESIDE ([[substance_class:psychoactive/psychedelic]] [[glossary:peer-support]] line)
* '''ICEERS:''' International Center for Ethnobotanical Education, Research and Security — legal and safety resources for ayahuasca users
If persistent psychological [[glossary:disturbance]] follows use — including [[effect:anxiety]], [[effect:depersonalization|depersonalisation]], or mood instability lasting more than two weeks — consult a mental health professional with experience in psychedelic-related concerns.
{{/Recovery}}
===Receptor targets of B. caapi alkaloids===
'''Harmine''' is a potent, reversible [[glossary:mao-a]] [[glossary:inhibitor]] with Ki in the low nanomolar range — the primary [[glossary:mechanism-of-action|pharmacological action]] of B. caapi{{cite|doi=10.1093/toxsci/kfaf118|anchor=9baa982e}}{{cite|doi=10.3390/biom12111618|anchor=01934817}}. At higher concentrations, [[substance:harmine]] acts as a [[glossary:5-ht2a]] [[glossary:agonist|receptor agonist]] and augments electrically evoked [[glossary:efflux|dopamine efflux]] in the [[glossary:nucleus-accumbens]] shell via a presynaptic 5-HT₂A [[glossary:receptor]]-dependent mechanism that is independent of its MAOI activity{{cite|doi=10.1177/0269881112463125|anchor=7cae2011}}. Harmine is also a potent inhibitor of DYRK1A (dual-specificity tyrosine-phosphorylated and regulated kinase 1A), a target of potential relevance to neurodevelopmental and neurodegenerative disease research{{flag|citation-needed}}.
'''Harmaline''' is a weaker reversible MAO-A inhibitor{{cite|doi=10.1093/toxsci/kfaf118|anchor=a645854e}}{{cite|doi=10.3390/biom12111618|anchor=a7d30993}} with documented [[glossary:5-ht1a]] receptor involvement in animal [[glossary:hypothermia]] models{{cite|pubmed=8577810|anchor=457e72af}}. It also exhibits anti-inflammatory activity via COX [[glossary:inhibition]], nitric oxide pathway suppression, and Nrf-2/[[substance_class:pharmacological/antioxidant]] signaling [[glossary:activation]], with reductions in IL-1β documented in preclinical models{{cite|doi=10.1007/s00210-025-04220-w|anchor=509f2435}}.
'''Tetrahydroharmine''' (THH) is a weak MAO-A inhibitor and a [[substance_class:pharmacological/serotonin-reuptake-inhibitor]] (SSRI-like action), contributing to mood [[glossary:modulation]] within the [[substance:ayahuasca]] alkaloid complex{{cite|doi=10.3390/biom12111618|anchor=15a2e170}}.
===MAO-A inhibition and oral DMT activation===
MAO-A normally deaminates [[substance:dmt]] rapidly in the gastrointestinal tract and liver, rendering it orally inactive. Harmine from B. caapi inhibits this [[glossary:enzyme]], enabling DMT from admixture plants to reach systemic circulation and cross the [[glossary:blood-brain-barrier]]{{cite|pubmed=12660312|anchor=f908e620}}{{cite|doi=10.1093/toxsci/kfaf118|anchor=9348ea14}}. [[glossary:plasma]] data indicate that this action is predominantly peripheral (gastrointestinal and hepatic) — harmine [[glossary:plasma-concentration|plasma levels]] were negligible after oral ayahuasca administration, suggesting that peripheral MAO-A inhibition alone suffices to enable DMT [[glossary:absorption]]{{cite|pubmed=12660312|anchor=09e28d7a}}. The DMT–harmine [[glossary:pharmacokinetic-interaction]] is bidirectional: harmine reduces DMT [[glossary:first-pass-metabolism]] while DMT alters harmine [[glossary:pharmacokinetics]]{{cite|doi=10.1016/j.biopha.2025.117908|anchor=b22a6d26}}.
===Pharmacokinetics===
====Oral ayahuasca====
From a [[glossary:double-blind]] [[glossary:placebo|placebo-controlled]] study (n=18, doses of 0.6 and 0.85 mg DMT/kg body weight){{cite|pubmed=12660312|anchor=51fda46c}}:
* '''DMT Cmax:''' 12.14 ng/mL (low dose); 17.44 ng/mL (high dose)
* '''DMT Tmax:''' 1.5 h (median, both doses)
* '''Subjective effects:''' peak at 1.5–2 h; resolution within 4–6 h
From ritual ayahuasca [[glossary:ingestion]] (n=15){{cite|pubmed=8889686|anchor=f611863f}}:
* '''Harmine Cmax:''' up to 222.3 ng/mL
* '''THH Cmax:''' up to 134.5 ng/mL
* '''Harmaline Cmax:''' up to 9.4 ng/mL (consistently the lowest β-carboline)
Saliva and serum analysis (n=14 religious users) demonstrated that β-carboline cmax values were higher in saliva than in serum, with mean [[glossary:receptor-residence-time|residence time]] in serum 1.5–3.0× longer than in saliva{{cite|doi=10.1002/dta.2955|anchor=5b1e5c9d}}.
====Buccal DMT+harmine formulation====
A factorial dose-escalation study of buccal DMT (0–120 mg) combined with harmine (0–180 mg) reported peak DMT cmax of 33 ng/mL and harmine [[glossary:cmax]] of 49 ng/mL, with [[index:effects|subjective effects]] lasting 4–5 hours and tmax increasing with [[glossary:dose-escalation]] for both compounds{{cite|doi=10.1016/j.biopha.2025.117908|anchor=97e1e798}}.
====CYP involvement====
Harmine inhibits [[glossary:cyp2d6]] and [[glossary:cyp3a4]] [[glossary:in-vitro|in vitro]], providing a mechanistic basis for herb-[[glossary:drug-interaction|drug interactions]] beyond MAO-A inhibition. The clinical significance of this CYP inhibition relative to the MAO-A inhibitory effect has not been established in published clinical pharmacokinetic studies{{flag|safety-citation-needed}}.
===Neurogenesis===
Harmine, THH, [[substance:harmaline]], and the harmine [[glossary:metabolite]] harmol all stimulate adult [[glossary:neurogenesis]] in vitro — promoting neural stem cell proliferation, migration, and differentiation in mouse brain neurospheres from both the subventricular zone and subgranular zone{{cite|doi=10.1038/s41598-017-05407-9|anchor=1d3adbf0}}. This [[glossary:neuroplasticity]] mechanism provides a candidate biological [[glossary:substrate]] for the [[substance_class:psychoactive/antidepressant]] effects observed with ayahuasca and its constituent β-carbolines.
===Neuroimaging===
Functional MRI studies demonstrate that ayahuasca produces significant decreases in [[glossary:default-mode-network]] (DMN) activity — including the posterior cingulate [[glossary:cortex]] (PCC)/precuneus and medial [[glossary:prefrontal-cortex]] — with decreased connectivity within the PCC/precuneus{{cite|doi=10.1371/journal.pone.0118143|anchor=6cf8c585}}. [[glossary:systematic-review]] of classical [[substance_class:psychoactive/hallucinogen]] neuroimaging confirms acute excitation of frontolateral and frontomedial cortex, medial temporal lobe, and occipital cortex alongside DMN inhibition{{cite|doi=10.1016/j.neubiorev.2016.10.026|anchor=07546fb3}}. Post-acute neurometabolic changes, including [[effect:mindfulness-enhancement]] capacities and persistent default mode network [[glossary:modification|modifications]], have been documented at 24 hours post-administration{{cite|doi=10.1093/ijnp/pyx036|anchor=954101a4}}.
===Open questions===
* No pharmacokinetic data exist for B. caapi-only preparations (without DMT admixture). All published human PK data derive from ayahuasca or standardized DMT+harmine formulations.
* The clinical significance of harmine's CYP2D6 and CYP3A4 inhibition relative to its MAO-A inhibition for herb-drug interaction profiling remains uncharacterized.
* Whether the neurogenesis stimulated by B. caapi alkaloids in vitro translates to clinically relevant structural neuroplasticity in humans has not been established.
[[substance:dmt]] — the primary psychoactive compound in full [[substance:ayahuasca]] preparations, contributed by admixture plants — is a '''Schedule I substance''' under the 1971 United Nations [[glossary:convention-on-psychotropic-substances]]{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=8588f4fe}}. The β-carboline alkaloids in B. caapi ([[substance:harmine]], [[substance:harmaline]], tetrahydroharmine) are [[glossary:unscheduled|not scheduled]] under any international treaty. The ayahuasca brew itself is not explicitly named in [[glossary:drug-control|international drug control]] conventions. This creates complex jurisdictional variation: the vine is uncontrolled, but preparations containing DMT from admixture plants fall under national drug laws in most countries. Religious exemption jurisprudence provides the primary legal pathway for authorised use.
===Treaty considerations===
The disjunction between international scheduling of DMT and the unscheduled status of B. caapi and the ayahuasca brew creates the principal legal ambiguity. B. caapi vine contains no DMT — its β-carboline alkaloids are not controlled under any international treaty. However, traditional preparations combining B. caapi with DMT-containing plants yield a brew containing a [[glossary:schedule-i]] substance, placing it under national drug control frameworks in most jurisdictions. Religious exemption jurisprudence (US RFRA, Brazilian CONAD, Canadian Section 56) provides the primary legal pathway for authorised use.
| Jurisdiction | Status | Notes |
|---|---|---|
| United States (federal) | DMT: Schedule I | Ayahuasca illegal via DMT content. B. caapi vine not federally scheduled. RFRA upheld for UDV in ''Gonzales v. O Centro'' (2006). Church of Gaia received DEA religious exemption (2023).{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=4fe1de19}} |
| United States (state) | Variable | No state has independently scheduled B. caapi vine. Federal DMT scheduling supersedes state-level permissiveness.{{flag|citation-needed}} |
| Brazil | Legal for religious use | CONAD recognised ayahuasca for religious use (1987); 2010 resolution clarified rules. Commercial and non-religious use remain prohibited.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=8278bb39}} |
| Peru | National cultural heritage | Declared cultural heritage in 2008. Significant legal protection for traditional use; ayahuasca tourism operates commercially.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=8be62fba}} |
| Colombia | No specific legislation | No specific legislation regulating ayahuasca. Retreats operate without legal interference in practice.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=9b445703}} |
| Canada | DMT: Schedule III (CDSA) | Ayahuasca illegal by default. Religious exemption possible via Section 56 of CDSA.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=725b669d}} |
| United Kingdom | DMT: Class A | All DMT-containing preparations strictly prohibited. No religious exemption established.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=21ef9aaf}} |
| Spain | Personal possession decriminalised | Import, sale, and cultivation remain illegal. Highest number of ayahuasca-related legal incidents in Europe.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=6d2598e0}} |
| Portugal | Possession decriminalised | All drug possession decriminalised (2001). Import, sale, and cultivation of ayahuasca remain illegal.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=482556c9}} |
| France | Prohibited | Regulatory lists include ayahuasca preparation plants. Full prohibition in effect.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=77a55ac9}} |
| Netherlands | DMT: List I (Opium Act) | B. caapi vine not scheduled. Legal status of ayahuasca brew ambiguous; court outcomes have varied.{{flag|citation-needed}} |
| Germany | DMT controlled (BtMG) | Ayahuasca illegal. No religious exemption established.{{flag|citation-needed}} |
| Australia | DMT: Schedule 9 | Ayahuasca illegal. State-level enforcement variation may exist.{{flag|citation-needed}} |
[[substance:dmt]] — the primary psychoactive in full [[substance:ayahuasca]] preparations — is a [[glossary:schedule-i]] substance under the 1971 UN [[glossary:convention-on-psychotropic-substances]]{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=d20fd176}}. B. caapi's β-carboline alkaloids ([[substance:harmine]], [[substance:harmaline]], tetrahydroharmine) are [[glossary:unscheduled|not scheduled]] under any international treaty. The brew occupies a legal grey zone in most countries: the vine is uncontrolled, but the DMT it enables via admixture plants falls under national drug law.
Brazil has recognized religious ayahuasca use since 1987; Peru declared it national cultural heritage in 2008{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=69c9bd23}}. In the United States, ayahuasca is federally illegal as a DMT preparation, though the 2006 Supreme Court ruling in ''Gonzales v. O Centro Espírita Beneficente União do Vegetal'' upheld religious exemptions, and the Church of Gaia received a [[glossary:drug-enforcement-administration|DEA]] exemption in 2023{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=3ab8ab3c}}. In the UK and France, DMT-containing preparations are fully prohibited. Spain and Portugal have decriminalized [[glossary:possession|personal possession]]; import, sale, and cultivation remain illegal{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=535380c5}}. Canada classifies DMT as a controlled substance but allows religious exemptions via Section 56 of the [[glossary:controlled-drugs-and-substances-act|CDSA]]{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=cb651860}}.
{{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}}
===Treaty considerations===
B. caapi vine contains no DMT and its alkaloids are not internationally scheduled. Traditional preparations combining it with DMT-containing plants produce a brew containing a Schedule I substance, placing it under national [[glossary:drug-control]] in most countries. Religious exemption frameworks — the US RFRA, Brazilian CONAD recognition, and Canadian Section 56 — provide the primary legal pathway for authorised use.
The experiential character of B. caapi preparations diverges sharply depending on whether [[substance:dmt]]-containing admixture plants are present. Classic [[substance:ayahuasca]] (B. caapi combined with ''Psychotria viridis'') produces a dense, multi-layered state integrating intense perceptual [[glossary:modification]], emotional and cognitive amplification, prominent gastrointestinal [[glossary:activation]], and introspective depth — a combination unlike any single-compound [[glossary:psychedelic-experience]]. B. caapi alone, by contrast, is described in traditional accounts as producing primarily somatic and introspective effects without prominent visual [[glossary:hallucination]]. Set, setting, and the ceremonial container exert unusually strong influence on experience quality; batch-to-batch alkaloid variability (RSD 78.9–170%) further ensures that no two administrations are pharmacologically identical.
Ayahuasca occupies a distinct position among [[glossary:serotonergic-psychedelics]]. Where oral psilocybin or [[substance:lsd]] produces effects primarily through direct [[glossary:5-ht2a]] agonism, ayahuasca's pharmacology is a multi-compound interaction — reversible [[glossary:mao-a]] [[glossary:inhibition]] enabling oral DMT activity, layered with THH's SSRI-like [[substance_class:pharmacological/serotonin-reuptake-inhibitor]]. This mechanistic complexity, combined with the pronounced somatic and emetic component, distinguishes it from all [[glossary:synthetic]] [[substance_class:chemical/tryptamine]] and [[substance_class:chemical/lysergamide]] experiences.
===Toxicity===
No published human [[glossary:lethal-dose|LD50]] data exist for B. caapi or [[substance:ayahuasca]]. A systematic review found no post-mortem study in which toxicological examination and autopsy findings together suggested [[glossary:fatality|lethality]] from ayahuasca alone{{cite|doi=10.3390/jcm11041147|anchor=0ad151e5}}. Cytotoxicity studies in microglial cell lines showed concentration-dependent reduction in cell viability at [[substance:harmine]] concentrations of 75.5–302 µM{{cite|doi=10.3390/molecules27082500|anchor=1c279325}}, but these concentrations far exceed therapeutic [[glossary:plasma-concentration|plasma levels]] (harmine Cmax in vivo: up to 222.3 ng/mL, approximately 1 µM){{cite|pubmed=8889686|anchor=6c7bf3e4}}.
====Acute adverse effects====
The most frequently reported acute physiological effect is '''nausea and vomiting''', occurring in a majority of users in some surveys{{cite|doi=10.1590/1516-4446-2020-0913|anchor=f62f3279}}. In controlled clinical settings, a diastolic [[glossary:blood-pressure]] increase of approximately 9 mmHg was observed at higher doses (0.85 mg [[substance:dmt]]/kg), along with mild [[glossary:sympathomimetic|sympathomimetic effects]] including [[effect:pupil-dilation]], prolactin [[glossary:elevation]], and cortisol elevation{{cite|pubmed=12660312|anchor=5828368c}}{{cite|doi=10.1097/JCP.0b013e31823607f6|anchor=7c0cc1f3}}. Transient lymphocyte [[glossary:modulation]] (NK cell increase, CD4 and CD3 decrease) has been documented, returning to baseline within 24 hours{{cite|doi=10.1097/JCP.0b013e31823607f6|anchor=c149b249}}.
A [[glossary:case-report]] documented [[glossary:intoxication]] following ayahuasca consumption with altered perception and thought processes{{cite|doi=10.1016/j.rcpeng.2025.10.009|anchor=6920dfc7}}{{flag|additional-citations-needed}}.
====Hepatic safety====
No significant alteration in liver function tests (ALT, AST, bilirubin, creatinine, urea, LDH, alkaline phosphatase, GGT) was found in 22 chronic ayahuasca users consuming the preparation twice monthly for at least one year{{cite|doi=10.1080/02791072.2018.1557355|anchor=080221eb}}{{flag|additional-citations-needed}}.
====Contaminant and adulterant risk====
No systematic studies on pesticide contamination, heavy metal content (lead, cadmium, arsenic, mercury), or mycotoxin contamination in commercial B. caapi preparations have been published{{flag|safety-citation-needed}}. Batch-to-batch alkaloid variability is extreme (RSD 78.9–170%), meaning a dose calibrated on one batch may deliver substantially different alkaloid quantities from another{{cite|doi=10.3390/plants9070870|anchor=8743a566}}. No standardization framework, Certificate of Analysis requirement, or ISO/IEC-accredited testing program exists for commercial B. caapi products. Commercially sold preparations may contain variable and unlabeled amounts of active alkaloids{{cite|doi=10.3390/jcm11041147|anchor=44c02e92}}{{cite|doi=10.1016/j.jchromb.2019.06.014|anchor=5c5c3ffd}}. This constitutes a practical safety gap — particularly for non-ceremonial use where experienced dose calibration by a traditional practitioner is absent.
===Psychological risks===
Acute [[effect:anxiety]], transient [[effect:confusion]], and panic reactions are commonly reported even at standard ayahuasca doses{{cite|pubmed=16149336|anchor=01cbd24d}}. In a cross-sectional study of 614 religious users, the most frequent [[glossary:adverse-effects]] were transient gastrointestinal symptoms; a minority reported being "very negatively affected" by persistent adverse effects{{cite|doi=10.1590/1516-4446-2020-0913|anchor=fad76507}}. Adverse effects were more frequent in participants with pre-existing psychiatric diagnoses ([[effect:depression]], anxiety), although psychiatric [[glossary:medication]] use was not statistically associated with increased adverse effect frequency in this sample{{cite|doi=10.1590/1516-4446-2020-0913|anchor=817daed3}}.
Risk of acute adverse psychological reactions is elevated in individuals with personal or family history of psychotic [[glossary:disorder|disorders]], bipolar disorder type I, or severe psychiatric illness{{cite|doi=10.1016/j.tmaid.2021.102206|anchor=adb08002}}{{cite|doi=10.2174/1570159x16666180125095902|anchor=cd29f67b}}. A scoping review of traveller risks identified psychological adverse reactions as the primary documented concern in non-ceremonial settings{{cite|doi=10.1016/j.tmaid.2021.102206|anchor=c65ef7c2}}. No documented cases of HPPD (HPPD) specific to ayahuasca were identified in the literature reviewed{{flag|citation-needed}}.
===Tolerance and dependence===
====Tolerance====
Long-term ritual users consuming ayahuasca at least twice monthly for years show no [[effect:cognitive-impairment]] and no pattern of addiction-related problems{{cite|doi=10.1371/journal.pone.0042421|anchor=dff42f7e}}. Preserved or improved cognitive function — including enhanced working memory — has been confirmed in cross-sectional study of long-term users versus beginners{{cite|doi=10.1007/s00406-024-01817-9|anchor=c002d831}}. Naive users assessed at 1 and 6 months after first ayahuasca use showed improvements in mental health measures{{cite|doi=10.1038/s41598-020-61169-x|anchor=7e3f5ca6}}.
[[glossary:tolerance]] to the [[substance_class:psychoactive/psychedelic]] effects of DMT (the primary visionary component in full ayahuasca) develops with repeated acute dosing. Tolerance to MAO-A [[glossary:inhibition]] by harmine has not been systematically studied.
====Dependence====
No published evidence of physical dependence or [[glossary:withdrawal]] from B. caapi or ayahuasca exists{{cite|doi=10.2174/1570159x16666180125095902|anchor=3f8f7fcd}}{{cite|doi=10.1371/journal.pone.0042421|anchor=cd0bf65e}}. Regular ayahuasca use does not produce the addiction-related problems characteristic of substances of abuse. No withdrawal timeline has been characterized in published literature.
===Drug interactions===
B. caapi's harmine and [[substance:harmaline]] are reversible MAO-A [[glossary:inhibitor|inhibitors]]. This mechanism creates the primary herb-[[glossary:drug-interaction]] risk profile for any preparation containing B. caapi.
====Serotonergic agents====
MAO-A inhibition combined with [[substance_class:pharmacological/serotonin-reuptake-inhibitor]] or serotonin release increases [[glossary:serotonin|synaptic serotonin]] concentrations, creating a mechanistic basis for '''serotonin syndrome''' ([[glossary:serotonin-syndrome]]) — a potentially life-threatening condition characterized by [[glossary:hyperthermia]], [[glossary:agitation]], clonus, and hyperreflexia. Affected drug classes include SSRIs, SNRIs, triptans, [[substance:tramadol]], meperidine, and [[substance:dextromethorphan]]{{cite|doi=10.3390/biom12111618|anchor=766fb995}}{{cite|doi=10.1093/toxsci/kfaf118|anchor=f97e0458}}. Clinical case reports for serotonin syndrome specifically from B. caapi combined with SSRIs were not confirmed in the literature reviewed; the interaction [[glossary:severity]] rating is based on mechanistic [[glossary:inference]] from the MAOI pharmacology class{{flag|safety-citation-needed}}.
====Tyramine-containing foods====
MAO-A normally catabolizes dietary tyramine (present in aged cheeses, cured meats, fermented products); inhibition may produce excessive sympathomimetic response and hypertensive crisis. B. caapi produces reversible rather than irreversible MAO-A inhibition, and its MAOI effect is relatively transient. In a risk assessment of 614 religious users, no hypertensive crises were documented{{cite|doi=10.1590/1516-4446-2020-0913|anchor=fd3ed424}}{{flag|additional-citations-needed}}. The traditional dietary restrictions (''dieta'') observed before ayahuasca ceremonies are partly grounded in this interaction mechanism. The magnitude of tyramine interaction specific to reversible MAO-A inhibition from B. caapi versus irreversible pharmaceutical MAOIs remains uncharacterized{{flag|safety-citation-needed}}.
====Sympathomimetics====
[[substance:amphetamine|Amphetamines]], [[substance:cocaine]], and other sympathomimetic agents may produce augmented dopaminergic and noradrenergic effects via reduced MAO-A catabolism. This is a mechanistic inference; no clinical case reports specific to ayahuasca combined with sympathomimetics were retrieved{{flag|safety-citation-needed}}.
====CYP2D6 and CYP3A4 substrates====
Harmine inhibits [[glossary:cyp2d6]] and CYP3A4 in vitro, potentially elevating plasma levels of co-administered medications metabolized by these [[glossary:enzyme|enzymes]] — including certain [[substance_class:psychoactive/antipsychotic|antipsychotics]], [[substance_class:psychoactive/antidepressant|antidepressants]], and [[substance_class:psychoactive/opioid|opioids]]. Clinical significance has not been established in published pharmacokinetic studies{{flag|safety-citation-needed}}.
====Lithium====
Anecdotal reports in the broader psychedelic literature suggest [[glossary:seizure]] and cardiac risk with [[substance:lithium]] combined with psychedelics. No clinical case report for lithium combined with ayahuasca was retrieved in this literature review{{flag|safety-citation-needed}}.
===Contraindications===
====Absolute====
* '''Personal history of psychotic disorders or bipolar disorder type I:''' Elevated risk of acute adverse psychological reactions, including [[glossary:psychosis]] precipitation{{cite|doi=10.1016/j.tmaid.2021.102206|anchor=86dd10f9}}{{cite|doi=10.2174/1570159x16666180125095902|anchor=e8170af3}}
* '''Concurrent serotonergic medication use''' (SSRIs, SNRIs, triptans, tramadol, dextromethorphan, and other serotonergic agents): Mechanistic risk of serotonin syndrome via MAO-A inhibition combined with [[glossary:reuptake|serotonin reuptake]] [[glossary:blockade]] or release{{cite|doi=10.3390/biom12111618|anchor=eb308010}}
====Relative====
* '''Severe cardiovascular disease:''' Mild diastolic blood pressure increase (~9 mmHg) and sympathomimetic [[glossary:activation]] documented at standard doses{{cite|pubmed=12660312|anchor=dc21f416}}
* '''Family history of psychotic disorders:''' Elevated [[glossary:psychological-risk]] based on clinical risk assessment literature{{cite|doi=10.2174/1570159x16666180125095902|anchor=9736d815}}
* '''Concurrent lithium use:''' Uncharacterized seizure and cardiac risk reported anecdotally in the broader psychedelic literature{{flag|safety-citation-needed}}
* '''Pregnancy:''' No reproductive safety data exist for B. caapi or ayahuasca; MAO-A inhibition and serotonergic modulation present theoretical fetal risk{{flag|safety-citation-needed}}
* '''Hepatic impairment affecting CYP2D6/CYP3A4 metabolism:''' Potential for altered harmine [[glossary:metabolism]] and prolonged MAO-A inhibitory effect{{flag|safety-citation-needed}}
====Detection====
DMT's short [[glossary:plasma]] [[glossary:half-life]] limits direct urinary detection. Harmala alkaloids (harmine, harmaline, THH) serve as more reliable biomarkers for identifying ayahuasca exposure in forensic urine drug screens{{cite|doi=10.1093/jat/bky105|anchor=3c166053}}. Hair analysis via dispersive liquid-liquid microextraction can detect DMT, harmine, harmaline, and THH at pg/mg concentrations, with β-carbolines detected at higher concentrations than DMT in hair samples{{cite|doi=10.1016/j.talanta.2026.129455|anchor=2afd41b0}}.
[[substance:dmt]] — the primary psychoactive compound in full [[substance:ayahuasca]] preparations contributed by admixture plants — is a '''Schedule I substance''' under the 1971 United Nations [[glossary:convention-on-psychotropic-substances]]{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=f74dc84f}}. The β-carboline alkaloids in B. caapi ([[substance:harmine]], [[substance:harmaline]], tetrahydroharmine) are '''not scheduled''' under the 1971 Convention. The ayahuasca brew itself is not explicitly scheduled under [[glossary:drug-control|international drug control]] treaties. The B. caapi vine and [[glossary:plant-material]] are not controlled under the 1961 UN Single Convention on Narcotic Drugs or the 1988 Convention Against Illicit Traffic. This creates complex jurisdictional variation in which the plant is uncontrolled but preparations containing DMT from admixture plants fall under national drug laws.
===Treaty considerations===
The disjunction between international scheduling of DMT and the [[glossary:unscheduled|unscheduled status]] of both B. caapi and the ayahuasca brew itself creates the principal legal ambiguity. B. caapi vine contains no DMT — its β-carboline alkaloids are not controlled under any international treaty. However, the traditional preparation combining B. caapi with DMT-containing admixture plants yields a brew that contains a [[glossary:schedule-i]] substance, placing it under national drug control frameworks in most jurisdictions. Religious exemption jurisprudence (US RFRA, Brazilian CONAD, Canadian Section 56) provides the primary legal pathway for authorized use.
| Jurisdiction | Classification | Key provisions |
|---|---|---|
| United States (federal) | DMT: Schedule I (Controlled Substances Act) | Ayahuasca is federally illegal via DMT content. B. caapi vine itself is not federally scheduled; its sale as a botanical product exists in a legal grey area. RFRA provides constitutional basis for religious exemption — upheld in ''Gonzales v. O Centro Espírita Beneficente União do Vegetal'' (2006). Church of Gaia received DEA religious exemption in 2023.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=8ade4084}} |
| United States (state-level) | Variable | Some states may have analog act implications for B. caapi preparations{{flag|citation-needed}}. No state has independently scheduled the B. caapi vine. Federal scheduling of DMT supersedes state-level permissiveness where applicable. |
| Brazil | Legal for religious use | CONAD recognized ayahuasca for religious and ritual use in 1987; 2010 resolution established clearer rules. Commercial sale and non-religious use remain prohibited.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=a69a6b13}} |
| Peru | National cultural heritage | Ayahuasca declared part of national cultural heritage in 2008. Significant legal protection for traditional use; ayahuasca tourism operates as a major industry. Specific regulations for non-indigenous commercial use are evolving.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=600eaaf3}} |
| Colombia | No specific legislation | No specific legislation regulating ayahuasca. Ayahuasca retreats operate without legal interference in practice.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=d8b95e84}} |
| Canada | DMT: Schedule III (Controlled Drugs and Substances Act) | Ayahuasca illegal by default. Religious exemption possible via Section 56 of CDSA; some Canadian religious groups have pursued this pathway.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=41678c71}} |
| United Kingdom | DMT: Class A (Misuse of Drugs Act 1971) | Ayahuasca and all DMT-containing preparations strictly prohibited. No religious exemption established.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=0674d3c1}} |
| Spain | Personal possession decriminalized | Possession decriminalized under Spanish drug policy. Import, sale, and cultivation remain illegal. Spain has the highest number of legal incidents related to ayahuasca in Europe.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=6547c8cf}} |
| Portugal | Possession decriminalized | All drug possession decriminalized under 2001 law. Import, sale, and cultivation of ayahuasca remain illegal.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=fcc1e6e0}} |
| France | Prohibited | Regulatory lists include plants used in ayahuasca preparation. Full prohibition in effect.{{cite|url=https://www.iceers.org/ayahuasca-legal-status/|anchor=b7cf2598}} |
| Netherlands | DMT: List I (Opium Act) | B. caapi vine not scheduled. Legal status of ayahuasca brew is ambiguous; court cases have produced varying outcomes.{{flag|citation-needed}} |
| Germany | DMT controlled (Betäubungsmittelgesetz) | Ayahuasca illegal. No religious exemption established.{{flag|citation-needed}} |
| Australia | DMT: Schedule 9 (Poisons Standard) | Ayahuasca illegal. State-level variation in enforcement may exist.{{flag|citation-needed}} |
Evidence Changes38 added
+Santos TAC et al. 2025— Dated Phylogeny of Banisteriopsis (Malpighiaceae) Suggests an Ancient Colonization of the Cerrado and No Evidence of Human Manipulation in the Origin of B. caapi
+Callaway JC et al. 1996— Quantitation of N,N-dimethyltryptamine and harmala alkaloids in human plasma after oral dosing with ayahuasca
+ICEERS (International Center for Ethnobotanical Education, Research and Service) 2024— Ayahuasca Legal Status by Country
+Palhano-Fontes F, Barreto D, Onias H, Andrade KC, Novaes MM, et al. 2018— Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression: a randomized placebo-controlled trial
+Durante I, Dos Santos RG, Bouso JC, Hallak JE 2021— Risk assessment of ayahuasca use in a religious context: self-reported risk factors and adverse effects
+Bouso JC, González D, Fondevila S, et al. 2012— Personality, psychopathology, life attitudes and neuropsychological performance among ritual users of Ayahuasca: a longitudinal study
+Nižnanský Ľ et al. 2022— Ayahuasca as a Decoction Applied to Human: Analytical Methods, Pharmacology and Potential Toxic Effects
+Rossi GN, Guerra LTL, Baker GB, Dursun SM, Saiz JCB, Hallak JEC, Dos Santos RG 2022— Molecular Pathways of the Therapeutic Effects of Ayahuasca
+Santos BWL et al. 2020— Biodiversity of β-Carboline Profile of Banisteriopsis caapi and Ayahuasca, a Plant and a Brew with Neuropharmacological Potential
+Wittayakarn N, Tan YM, Choomalaiwong P, et al. 2025— Development of a physiologically based pharmacokinetic model of N,N-dimethyltryptamine, harmine, and their interactions from ayahuasca in rats and humans
+Riba J, Valle M, Urbano G, Yritia M, Morte A, Barbanoj MJ 2003— Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics
+Hamill J, Hallak JEC, Dursun SM, Baker GB 2018— Ayahuasca: Psychological and Physiologic Effects, Pharmacology and Potential Uses in Addiction and Mental Illness
+Frecska E, Bokor P, Winkelman M 2016— The Therapeutic Potentials of Ayahuasca: Possible Effects against Various Diseases of Civilization
+Riba J, Barbanoj MJ 2005— Bringing ayahuasca to the clinical research laboratory
+Davis CC, Anderson WR 2010— A complete generic phylogeny of Malpighiaceae inferred from nucleotide sequence data and morphology
+Chaubey S, Singh L 2025— Harmaline attenuates pain and inflammation: role of IL-1beta, oxidative stress, nitric oxide and cyclo-oxygenase
+Brierley DI, Davidson C 2013— Harmine augments electrically evoked dopamine efflux in the nucleus accumbens shell
+Souza RCZ, Zandonadi FS, Freitas DP, Tofoli LFF, Sussulini A 2019— Validation of an analytical method for the determination of the main ayahuasca active compounds
+Pires AP et al. 2009— Gas chromatographic analysis of dimethyltryptamine and beta-carboline alkaloids in ayahuasca, an Amazonian psychoactive plant beverage
+Yritia M, Riba J, Ortuño J, Ramirez A, Castillo A, et al. 2002— Determination of N,N-dimethyltryptamine and beta-carboline alkaloids in human plasma following oral administration of Ayahuasca
+Wang YH, Samoylenko V, Tekwani BL, et al. 2010— Composition, standardization and chemical profiling of Banisteriopsis caapi, a plant for the treatment of neurodegenerative disorders relevant to Parkinson's disease
+Santos BWL, Moreira DC, Bordes TKDS, Caldas ED 2022— Components of Banisteriopsis caapi, a Plant Used in the Preparation of the Psychoactive Ayahuasca, Induce Anti-Inflammatory Effects in Microglial Cells
+Palhano-Fontes F, Andrade KC, Tofoli LF, et al. 2015— The psychedelic state induced by ayahuasca modulates the activity and connectivity of the default mode network
+Dos Santos RG, Osório FL, Crippa JAS, Hallak JEC 2016— Classical hallucinogens and neuroimaging: A systematic review of human studies
+Morales-Garcia JA, de la Fuente Revenga M, Alonso-Gil S, et al. 2017— The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro
+Sampedro F, de la Fuente Revenga M, Valle M, et al. 2017— Assessing the Psychedelic After-Glow in Ayahuasca Users: Post-Acute Neurometabolic and Functional Connectivity Changes Are Associated with Enhanced Mindfulness Capacities
+Dos Santos RG, Valle M, Bouso JC, et al. 2011— Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine
+Egger K, Jareño Redondo J, Müller J, et al. 2025— Examining the pharmacokinetic and pharmacodynamic interaction of N,N-dimethyltryptamine and harmine in healthy volunteers: a factorial dose-escalation study
+Mello SM, Soubhia PC, Silveira G et al. 2019— Effect of Ritualistic Consumption of Ayahuasca on Hepatic Function in Chronic Users
+Houle SKD et al. 2021— Ayahuasca and the traveller: A scoping review of risks and possible benefits
+Fonseca AM, Dos Santos RG, de Medeiros LS, et al. 2025— Long-term ayahuasca use is associated with preserved global cognitive function and improved memory: a cross-sectional study with ritual users
+Jiménez-Garrido DF et al. 2020— Effects of ayahuasca on mental health and quality of life in naïve users: A longitudinal and cross-sectional study combination
+Santos FP et al. 2026— A dispersive liquid-liquid microextraction method for the determination of ayahuasca alkaloids in human hair
+Abdel-Fattah AF et al. 1995— Hypothermic effect of harmala alkaloid in rats: involvement of serotonergic mechanism
+Lanaro R, Mello SM, da Cunha KF, Silveira G et al. 2021— Kinetic profile of N,N-dimethyltryptamine and beta-carbolines in saliva and serum after oral administration of ayahuasca
+Estrella-Parra EA et al. 2025— Intoxication Associated with Ayahuasca Consumption, Characterization, and Comparative Analysis of the Beverage's Components: A Case Report
Data Field Changes1 changed · 15 unchanged
| Field | r1 | r2 | |
|---|---|---|---|
| Summary | (empty) | → | Banisteriopsis caapi is a South American liana (Malpighiaceae) whose β-carboline alkaloids act as reversible MAO-A inhibitors. It is the base vine of the ayahuasca decoction, where this MAO-A inhibition enables oral DMT bioavailability. |
Effects Profile Changes62 added
Added (62)
Temperature dysregulationbody
0.400.50
Dreaming enhancementperception
0.600.60
External hallucinationsperception
0.400.30
Geometryperception
0.500.40
Internal hallucinationsperception
0.500.40
Sleep-transition hallucinationsperception
0.500.40
Spatial disorientationperception
0.500.50
Vestibular distortionperception
0.500.50
Body highbody
0.500.60
Diarrheabody
0.600.70
Dizzinessbody
0.600.70
Excessive sweatingbody
0.400.50
Headachebody
0.300.30
Heart rate perception changesbody
0.400.40
Involuntary body movementsbody
0.600.70
Motor control impairmentbody
0.600.60
Nauseabody
0.800.90
Nystagmus (eye wobbles)body
0.500.60
Pain suppressionbody
0.300.30
Physical fatiguebody
0.500.70
Restlessnessbody
0.400.40
Salivationbody
0.400.50
Sedationbody
0.500.60
Spontaneous body sensationsbody
0.500.60
Stimulationbody
0.400.50
Tingling / electric sensationsbody
0.400.50
Tremblingbody
0.600.70
Vibrations / buzzingbody
0.500.50
Vomitingbody
0.700.80
Aesthetic enhancementthinking
0.500.40
Cognitive euphoriathinking
0.500.50
Cognitive fatiguethinking
0.500.60
Cognitive impairmentthinking
0.400.50
Confusionthinking
0.400.40
Creativity enhancementthinking
0.400.40
Decision impairmentthinking
0.400.40
Increased nature relatednessthinking
0.500.50
Introspection enhancementthinking
0.600.60
Openness enhancementthinking
0.500.50
Anxietyfeeling
0.500.40
Catharsisfeeling
0.600.50
Dysphoriafeeling
0.500.40
Emotional enhancementfeeling
0.600.60
Emotional labilityfeeling
0.500.50
Euphoriafeeling
0.500.50
Paranoiafeeling
0.400.30
Boundary dissolutionself
0.400.30
Depersonalizationself
0.400.30
Derealizationself
0.400.30
Emotional susceptibilityself
0.500.50
Present-moment absorptiontime
0.500.40
Temporal disorientationtime
0.400.40
Time alterationtime
0.500.50
Existential realizationtranspersonal
0.500.40
Noetic insighttranspersonal
0.500.40
Transpersonal feelingstranspersonal
0.500.40
Transpersonal visionstranspersonal
0.500.30
Unity and interconnectednesstranspersonal
0.500.40
Lucid dreaming enhancementawareness
0.500.40
Lucidity enhancementawareness
0.400.40
Personal insightawareness
0.600.60
Reality testing impairmentawareness
0.400.40