β‑Carbolines and Tryptamines in Ayahuasca

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This article is part of the Yaogará Ark, a living archive of Amazonian teacher plants and allied knowledge.

Abstract

Ayahuasca, a psychoactive brew originating in Western Amazonia, is central to the spiritual and medicinal practices of diverse Indigenous societies and, more recently, to transnational healing movements. Its distinctive psychoactivity arises from the synergy of two classes of plant-derived alkaloids: β-carbolines (notably harmine, harmaline, and tetrahydroharmine from Banisteriopsis caapi) and tryptamines (such as N,N-dimethyltryptamine [DMT] from Psychotria viridis or related species) (McKenna 1984a; Callaway et al. 2005 [1]; [2]). Scientifically, their interaction—specifically, the β-carboline-induced reversible inhibition of monoamine oxidase-A (MAO-A), facilitating DMT’s oral psychoactivity—has become emblematic of Amazonian plant knowledge’s biochemical sophistication ([1]; [3]; [4]).

This article synthesizes botanical classification, biogeography, cultural practice, and pharmacology with an emphasis on mechanism, traditional preparation, and contemporary conservation-ethics debates. It outlines how β-carboline inhibition of MAO-A and complementary serotonergic actions of tetrahydroharmine shape both the acute psychophysiological profile and emerging antidepressant interpretations of the brew ([1]; [2]; [3]; [4]; [8]; [9]). It also situates these findings within Indigenous knowledge transmission, ritual care, and current pressures on forest resources and intellectual sovereignty.

Botanical Classification

Primary taxa associated with β-carboline and tryptamine sources in ayahuasca contexts include:

  • Banisteriopsis caapi

    • Kingdom: Plantae
    • Family: Malpighiaceae
    • Genus: Banisteriopsis
    • Species: Banisteriopsis caapi
    • Common names: Ayahuasca vine, yagé, caapi
    • Role: Principal β-carboline source (harmine, harmaline, tetrahydroharmine) ([2]; [5])

  • Psychotria viridis

    • Kingdom: Plantae
    • Family: Rubiaceae
    • Genus: Psychotria
    • Species: Psychotria viridis
    • Common names: Chakruna, chacrona
    • Role: Primary DMT source in many cultural lineages ([1]; [4]; [5])

  • Diplopterys cabrerana

    • Kingdom: Plantae
    • Family: Malpighiaceae
    • Genus: Diplopterys
    • Species: Diplopterys cabrerana
    • Common names: Chaliponga, chagropanga
    • Role: Alternative or complementary DMT source in some regions (McKenna 1984a; [2])

While ayahuasca frequently denotes the ritual decoction itself, many Indigenous languages also apply the term to the vine Banisteriopsis caapi. In several traditions, the vine alone is prepared and administered, recognizing its psychoactivity and medicinal value independent of DMT admixtures ([1]).

Geographical Distribution and Habitat

Banisteriopsis caapi is native to the lowland rainforests of the Western and Northwestern Amazon, distributed across Brazil, Peru, Colombia, Ecuador, and adjacent regions. A robust woody liana, it thrives in humid tropical forest margins, secondary growth, and canopy gaps where climbing support and filtered light are available. Local cultivars and landraces are propagated clonally by cuttings in Indigenous and mestizo gardens, reflecting long-term co-management and domestication.

Psychotria viridis, a shrub of the Rubiaceae, is cultivated and semi-wild throughout overlapping regions of the Western Amazon. It prefers shaded understory habitats and enriched soils, frequently maintained near dwellings or in agroforestry mosaics to ensure a stable supply of young leaves with consistent alkaloid content. Diplopterys cabrerana (Malpighiaceae), another liana native to the western Amazon basin, occupies similar climbing habitats and is selected for leaves used as an alternative DMT source, with preference varying across linguistic and ritual lineages (McKenna 1984a; [2]).

Beyond their Amazonian centers of diversity, these taxa—and the brew’s practice—have diffused transnationally through networks of Indigenous exchange, mestizo curanderismo, and global ceremonial communities. This expansion has increased ex situ cultivation in subtropical and greenhouse environments and raised new questions about genetic provenance, alkaloid variability, and sustainable sourcing ([1]; [4]; [6]). Throughout, habitat considerations remain critical: wild harvesting of mature lianas can be ecologically disruptive due to slow regrowth, while garden-based cultivation supports resilience and continuity of ceremonial practice ([1]).

Ethnobotanical Context

Among Amazonian Indigenous peoples—such as the Shipibo-Conibo, Kichwa, Tukano, Yawanawá, and others—ayahuasca is traditionally used in collective healing, shamanic initiation, divination, and as an instrument for accessing non-ordinary states of consciousness ([1]). The mestizo populations of the region, as well as participants in expanding urban and neo-shamanic movements, have also incorporated ayahuasca in therapeutic and spiritual modalities, with local interpretations adapting to new contexts (Labate & Cavnar 2014).

Preparation practices, ceremonial frameworks, and interpretations of efficacy differ but all revolve around the drink’s vision-inducing potential. The effect is attributed both to the spiritual agency of the plants and, increasingly in biomedical explanations, to their neurochemical properties. Notably, some traditional applications involve B. caapi alone, recognizing its own psychoactivity and medicinal value ([1]).

Transmission of ayahuasca knowledge involves both vertical (parent to child, apprentice to shaman) and horizontal (peer, intracommunity) mechanisms. Storytelling, direct apprenticeship, and ritual participation facilitate knowledge retention in Indigenous contexts, while formal certification, publications, and intercultural workshops have emerged among mestizo and global practitioners (Labate & Cavnar 2014). In many communities, dietas and song traditions (icaros) are the principal pedagogical media; they encode plant-specific instructions, healing protocols, and ethical orientations. The contemporary movement—clinical researchers, churches, and retreat centers—contributes new vocabularies (neurochemistry, psychiatry) while drawing on ancestral frameworks of ritual care, protection, and reciprocity.

Phytochemistry and Pharmacology

The ayahuasca pharmacological profile derives from an interplay between β-carbolines in the vine and tryptamines in the leaf admixture.

  • β-Carbolines: Harmine, harmaline, and tetrahydroharmine (THH) are the principal alkaloids in Banisteriopsis caapi ([2]; [5]). These compounds are reversible inhibitors of monoamine oxidase-A (MAO-A), an enzyme responsible for degrading monoamines in the gut and brain ([1]; [3]; [4]). By inhibiting intestinal and hepatic MAO-A, β-carbolines allow orally administered DMT to enter systemic circulation and access the central nervous system ([1]; [3]; [4]). THH also weakly inhibits MAO-A and acts on the serotonin transporter (SERT), increasing synaptic serotonin ([4]; [3]).

  • Tryptamines: N,N-Dimethyltryptamine (DMT), abundant in Psychotria viridis and sometimes Diplopterys cabrerana, acts primarily as a potent agonist at serotonin 5-HT2A receptors, which mediate psychedelic effects ([4]). DMT also interacts with additional serotonin receptor subtypes, sigma-1, and trace amine-associated receptors ([4]).

β-Carbolines

Harmine is typically the most abundant β-carboline in B. caapi, with strong, reversible MAO-A inhibitory activity. Harmaline, often present at lower concentrations, contributes similarly to MAO-A inhibition. Tetrahydroharmine (THH) is a weaker MAO-A inhibitor but displays additional pharmacology through SERT inhibition, potentially modulating mood and sensory gating ([1]; [3]; [4]).

  • Harmine: Most abundant β-carboline; strong MAO-A inhibitor; implicated in neural stem cell proliferation and possible antidepressant effects ([2]).
  • Harmaline: Similar in action to harmine; also inhibits MAO-A, though found at lower concentrations.
  • Tetrahydroharmine (THH): Less potent MAO-A inhibitor. Crucially, THH also inhibits the serotonin transporter (SERT), increasing synaptic serotonin ([4]; [3]).

In vitro and preclinical work suggests β-carbolines can influence adult neurogenesis and synaptic plasticity, offering mechanistic hypotheses for reported antidepressant effects and cognitive-emotional restructuring during and after ceremonies ([2]; [5]). These actions add to the central “enabling” role β-carbolines play in protecting DMT from first-pass deamination.

Tryptamines

DMT’s pharmacodynamics are dominated by 5-HT2A receptor agonism, a property shared across classical psychedelics. Its rapid onset and short half-life when administered parenterally contrast with the prolonged, phase-structured phenomenology of ayahuasca sessions. In the brew, DMT’s time course is shaped by co-administered β-carbolines—through MAO-A inhibition, possible transporter interactions, and pharmacokinetic modulation—producing a multi-hour experience with alternating somatic, visual, and cognitive-emotional waves ([3]; [4]; [8]; [9]).

Interaction

The crux of ayahuasca’s pharmacological action is the additive effect of β-carboline-induced MAO-A inhibition and DMT’s 5-HT2A agonism ([3]). Independently, DMT is rapidly deaminated and inactive orally; β-carbolines, in sufficient quantities, enable its central psychoactivity ([1]; [3]). Evidence suggests each compound also contributes separately, with β-carbolines exerting neurogenic, antidepressant, and mild CNS-stimulant actions ([2]).

Human pharmacokinetic studies with ritual brews indicate characteristic absorption, metabolism, and elimination profiles for harmine, THH, and DMT, with interindividual variability linked to brew composition and body mass ([8]). Clinical and neuroimaging literature further implicates serotonergic network modulation and salience network dynamics in the subjective and therapeutic effects observed under ceremonial conditions ([9]). The composite profile—MAO-A inhibition, SERT effects, and 5-HT2A agonism—helps explain both the intense visionary character and the reports of post-acute mood and cognitive changes.

Finally, while not part of Amazonian ayahuasca practice, Peganum harmala (Syrian rue) seeds are a noted Old World source of harmala alkaloids with pharmacological and toxicological profiles that parallel several actions of B. caapi β-carbolines ([10]). This comparative point underscores the broader ethnopharmacological significance of β-carbolines across cultures while highlighting ayahuasca’s distinctive synergy and ceremonial framing.

Traditional Preparation and Use

Ayahuasca is made by slow-boiling torn sections of B. caapi vine with the leaves of P. viridis (or substitutes) for hours to days. The resulting decoction is thick, brown, and bitter. Recipes and proportions vary across cultural lineages but generally ensure sufficient concentrations of both β-carbolines and DMT ([4]).

Several technical details and ritual norms are widely observed:

  • Plant selection and preparation

    • Vine sections are cleaned, pounded, or shredded to increase surface area. Leaf material is layered with vine in the pot.
    • Some lineages prefer particular vine morphotypes or maturities, linked to perceived “strength” and spiritual character.
    • Water is replenished repeatedly; the liquid is reduced to a concentrated brew, sometimes decanted and combined from multiple pots.

  • Adjuvants and adjustments

    • Mineral content and pH of water, length of reduction, and temperature control can influence alkaloid extraction.
    • Additional plants may be included according to lineage-specific purposes; some traditions prepare single-vine brews, recognizing the vine’s independent efficacy ([1]).

  • Ceremonial setting and conduct

    • Ceremonies are led by experienced practitioners (curandero, yachak, pajé), with sequenced dosing, attentive oversight, and the use of ritual songs (icaros), perfume, and tobacco.
    • Purging (vomiting) is interpreted as cleansing; visions, somatic sensations, and emotional catharsis are integrated into diagnosis and healing.
    • Safety protocols center on screening for contraindicated medications, preparing participants with dietary/behavioral guidelines, and providing post-session integration (Labate & Cavnar 2014; [9]).

Across traditions, practitioners emphasize that the “effect” arises from both biochemical synergy and the intentional, relational work of ceremony. Apprenticeship involves learning how to balance brew composition with the needs of a patient or group, including considerations of dose, timing, and song to guide the experience.

Conservation and Ethical Considerations

Demand for ayahuasca has increased markedly, raising concerns about overharvesting of B. caapi and biocultural appropriation ([1]). In some regions, wild lianas have been cut at unsustainable rates to supply urban and export markets, undermining local availability and forest structure. Conservation responses emphasize:

  • Sustainable cultivation

    • Community-managed gardens and agroforestry plots can supply vine and leaf material, reducing pressure on wild stands.
    • Clonal propagation preserves lineage-specific traits while enabling scaled cultivation for ceremonial and research contexts.

  • Biocultural equity

    • Respect for Indigenous intellectual property, support for community governance over ritual pharmacopoeia, and formal recognition of ceremonial expertise are central.
    • Ethical guidelines call for acknowledging the central role of Indigenous knowledge, securing informed consent, and supporting equitable benefit-sharing ([1]; [6]).

  • Safety and public health

    • Transparent screening for contraindicated pharmaceuticals (notably serotonergic agents), attention to set and setting, and practitioner training are strategic priorities in transnational contexts ([9]).
    • Research collaborations should align with community priorities, share data accessibly, and invest in local health and education capacity.

Broader policy frameworks—community protocols, access-and-benefit-sharing mechanisms, and place-based conservation—can help ensure that the expansion of ayahuasca interest supports, rather than displaces, the forest cultures that sustain it. Ultimately, the brew’s pharmacological sophistication is inseparable from ethical relationships with land, plants, and knowledge holders.

References

  1. Cumming, P. (2022). Monoamine Oxidase Inhibition by Plant-Derived β-Carbolines. Frontiers in Pharmacology. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.886408/full
  2. Morales-Garcia, J.A., et al. (2017). The alkaloids of Banisteriopsis caapi, the plant source of the Amazonian hallucinogen Ayahuasca, stimulate adult neurogenesis in vitro. Scientific Reports, 7, 5307. https://www.nature.com/articles/s41598-017-05407-9
  3. Riba, J., et al. (2003). The pharmacological interaction of compounds in ayahuasca. Revista Brasileira de Psiquiatria, 25(4), 363-370. https://www.scielo.br/j/rbp/a/s6rDBPvF99z7JccZf3gHNdz/?lang=en
  4. de Castro, A.L.S., et al. (2022). New Insights into the Chemical Composition of Ayahuasca. ACS Omega, 7(12), 10653–10667. https://pubs.acs.org/doi/10.1021/acsomega.2c00795
  5. Morales-García, J.A., et al. (2020). Investigation of Ayahuasca β-Carboline Alkaloids and Tryptamine in the mouse hippocampus. Molecules, 25(4), 989. https://pubmed.ncbi.nlm.nih.gov/32103256/
  6. Labate, B.C., & Cavnar, C. (2014). The Therapeutic Use of Ayahuasca. Springer. https://doi.org/10.1007/978-3-642-40426-9
  7. McKenna, D.J. (1984a). Monoamine oxidase inhibitors in Amazonian hallucinogenic plants: ethnobotanical, phytochemical, and pharmacological comparisons. J Ethnopharmacology, 10(2), 195-223. https://doi.org/10.1016/0378-8741(84)90003-5
  8. Callaway, J.C., et al. (2005). Pharmacokinetics of Hoasca alkaloids in healthy humans. Journal of Ethnopharmacology, 102(2), 241–245. https://doi.org/10.1016/j.jep.2005.05.002
  9. Politi, M., et al. (2021). Ayahuasca and its interaction with the human brain and body. Journal of Psychoactive Drugs, 53(4), 308-317. https://doi.org/10.1080/02791072.2021.1932028
  10. Moloudizargari, M., et al. (2013). Pharmacological and toxicological effects of Peganum harmala and its main alkaloids. Phytotherapy Research, 27(10), 1414-1428. https://doi.org/10.1002/ptr.4872

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