Medicinal Chemistry & Drug DevelopmentAyahuasca

Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and beta-carboline constituents of ayahuasca

This study (1984) investigated the alkaloid composition of field samples, consisting of the bark and leaf specimens used for brewing ayahuasca, which were also compared directly with other ayahuasca mixtures. Their compositions were generally similar, with little variation in the constituents of brews made by different ayahuasqueros.

Authors

  • McKenna, D.
  • Towers, G. H.
  • Abbott, F.

Published

Journal of Ethnopharmacology
individual Study

Abstract

Introduction

Ayahuasca is a hallucinogenic beverage derived by boiling the bark of the Malpighiaceous liana Banisteriopsis caapi together with the leaves of various admixture plants, viz. Psychotria viridis, Psychotria carthagenensis , or Diplopterys cabrerana . B. caapi contains harmine, harmaline, and tetrahydroharmine while the admixtures contain N,N-dimethyltryptamine (DMT). DMT, a potent hallucinogen, is inactive orally due to degradation by visceral monoamine oxidase (MAO). The beta-carbolines, however, are highly active reversible inhibitors of MAO and may protect the DMT from deamination by MAO and render it orally active. This mechanism has been proposed to underlie the oral activity of ayahuasca but has not been experimentally confirmed.

Methods

In the present study the constituents of the admixture plants and the alkaloids of eight ayahuasca samples from Peru were qualitatively and quantitatively analyzed using two-dimensional thin-layer chromatography (TLC), high pressure liquid chromatography (HPLC) and gas chromatography/mass spectrometry (GC/MS). Several B. caapi cultivars were quantitatively compared for variations in alkaloid content. Three admixture plants used rarely in the manufacture of ayahuasca were also screened for alkaloids. A selected sample of beta-carbolines were screened for activity as MAO inhibitors using an in vitro assay system, and structure/activity relationships were compared. Inhibition observed with single compounds was compared with the activity of selected samples of ayahuasca which were screened in the system and also with the activity of mixtures of beta-carbolines.

Results

The levels of DMT and beta-carbolines found in the ayahuasca samples examined in the present study were an order of magnitude greater than the levels reported in a previous study. Ayahuasca was found to be an extremely effective inhibitor of MAO in vitro and the degree of inhibition was directly correlated with the concentration of MAO-inhibiting beta-carbolines. Inhibition experiments using mixtures of beta-carbolines indicated that their effects in combination are additive, rather than synergistic or antagonistic.

Discussion

Implications of the results in understanding the pharmacology of ayahuasca are discussed.

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Research Summary of 'Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and beta-carboline constituents of ayahuasca'

Introduction

Ayahuasca is a traditional Amazonian hallucinogenic brew made by boiling the vine Banisteriopsis caapi with leaves of various admixture plants, commonly Psychotria viridis or Diplopterys cabrerana. Earlier chemical surveys identified three beta-carboline alkaloids in B. caapi—harmine, harmaline and tetrahydroharmine (THH)—and N,N-dimethyltryptamine (DMT) in the admixture plants. Because DMT is inactive orally due to degradation by visceral monoamine oxidase (MAO), it has been hypothesised that the beta-carbolines act as reversible MAO inhibitors to protect DMT from deamination and thereby enable the oral activity of the brew; however, this mechanism had not been experimentally demonstrated in ayahuasca preparations themselves. McKenna and colleagues set out to characterise the alkaloid constituents of multiple ayahuasca brews and their source plants and to test directly whether ayahuasca and its beta-carboline constituents inhibit MAO in vitro. The study combined ethnobotanical sampling of brews and plants from Peru with chromatographic identification and quantitation (two‑dimensional thin‑layer chromatography (TLC), high‑performance liquid chromatography (HPLC), and gas chromatography/mass spectrometry (GC/MS)), and assessed MAO inhibition using a rat‑liver cytosol assay to explore structure–activity relationships among selected beta‑carbolines and mixtures approximating ayahuasca composition.

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Study Details

  • Study Type
    individual
  • Journal
  • Compound
  • Topic
  • APA Citation

    McKenna, D. J., Towers, G., & Abbott, F. (1984). Monoamine oxidase inhibitors in South American hallucinogenic plants: tryptamine and beta-carboline constituents of ayahuasca. Journal of Ethnopharmacology, 10(2), 195-223. https://doi.org/10.1016/0378-8741(84)90003-5

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