Healthy VolunteersMedicinal Chemistry & Drug DevelopmentAyahuasca

Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics

This double-blind, placebo-controlled clinical study (n=18) investigated the subjective and cardiovascular effects and alkaloid pharmacokinetic properties of orally ingested ayahuasca (42-60mg DMT/70kg) in healthy volunteers. The time course of DMT plasma concentrations closely paralleled subjective effects. The pharmacokinetic results indicated a predominantly harmine-DMT interaction in the gastrointestinal tract and possibly in the liver.

Authors

  • Jordi Riba
  • Maria Barbanoj
  • Marta Valle

Published

Journal of Pharmacology and Experimental Therapeutics
individual Study

Abstract

Introduction

The effects of the South American psychotropic beverage ayahuasca on subjective and cardiovascular variables and urine monoamine metabolite excretion were evaluated, together with the drug's pharmacokinetic profile, in a double-blind placebo-controlled clinical trial. This pharmacologically complex tea, commonly obtained from Banisteriopsis caapi and Psychotria viridis, combines N,N-dimethyltryptamine (DMT), an orally labile psychedelic agent showing 5-hydroxytryptamine2A agonist activity, with monoamine oxidase (MAO)-inhibiting β-carboline alkaloids (harmine, harmaline, and tetrahydroharmine).

Methods

Eighteen volunteers with prior experience in the use of psychedelics received single oral doses of encapsulated freeze-dried ayahuasca (0.6 and 0.85 mg of DMT/kg of body weight) and placebo.

Results

Ayahuasca produced significant subjective effects, peaking between 1.5 and 2 h, involving perceptual modifications and increases in ratings of positive mood and activation. Diastolic blood pressure showed a significant increase at the high dose (9 mm Hg at 75 min), whereas systolic blood pressure and heart rate were moderately and nonsignificantly increased. Cmax values for DMT after the low and high ayahuasca doses were 12.14 ng/ml and 17.44 ng/ml, respectively. Tmax (median) was observed at 1.5 h after both doses. The Tmax for DMT coincided with the peak of subjective effects. Drug administration increased urinary normetanephrine excretion, but, contrary to the typical MAO-inhibitor effect profile, deaminated monoamine metabolite levels were not decreased.

Discussion

This and the negligible harmine plasma levels found suggest a predominantly peripheral (gastrointestinal and liver) site of action for harmine. MAO inhibition at this level would suffice to prevent first-pass metabolism of DMT and allow its access to systemic circulation and the central nervous system.

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Research Summary of 'Human pharmacology of ayahuasca: subjective and cardiovascular effects, monoamine metabolite excretion, and pharmacokinetics'

Introduction

DMT (N,N-dimethyltryptamine) is a tryptamine structurally related to serotonin that acts as a 5-hydroxytryptamine 2A (5-HT2A) receptor agonist and, when administered parenterally, produces rapid, intense but short-lived alterations of perception and self-experience together with autonomic activation. Ayahuasca is a botanical preparation that combines DMT-containing Psychotria viridis (or Diplopterys cabrerana) with Banisteriopsis caapi, a vine rich in β-carboline alkaloids (harmine, harmaline, tetrahydroharmine) that inhibit monoamine oxidase (MAO). It is widely hypothesised that inhibition of MAO by the β-carbolines prevents first-pass metabolism of orally ingested DMT and thereby permits DMT to reach the systemic circulation and the central nervous system; β-carbolines might also contribute centrally by inhibiting MAO in the brain or weakly blocking serotonin reuptake, but the site and extent of their action in humans remained unclear prior to this work. Riba and colleagues therefore set out to characterise the human pharmacology of ayahuasca in a controlled experimental setting. The study aimed to measure subjective and cardiovascular effects, urinary monoamine metabolite excretion as an in vivo index of MAO inhibition, and the pharmacokinetics of DMT and the principal β-carbolines after oral administration of encapsulated freeze-dried ayahuasca in healthy volunteers experienced with psychedelics.

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Study Details

References (4)

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