Received for publication February 3, 2003.
Revised February 24, 2003.
Accepted for publication March 13, 2003.

Human pharmacology of Ayahuasca: Subjective and cardiovascular effects, monoamine metabolite excretion and pharmacokinetics

Abstract

The effects of the South American psychotropic beverage ayahuasca on subjective and cardiovascular variables, urine monoamine metabolite excretion, and pharmacokinetics were evaluated in a double-blind placebo-controlled crossover 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-HT_2A agonist activity, with monoamine oxidase (MAO)-inhibiting -carboline alkaloids (harmine, harmaline, and tetrahydroharmine). 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 DMT/kg body weight) and placebo. Ayahuasca produced significant subjective effects peaking between 1.5 and 2 h, involving mainly 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), while systolic blood pressure and heart rate were moderately and non-significantly increased. C_max values for DMT after the low and high ayahuasca doses were 12.14 ng/ml and 17.44 ng/ml, respectively. T_max (median) was observed at 1.5 h after both doses. The T_max 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 metabolites were not found to be decreased. This and the negligible harmine plasma levels found suggest a predominantly peripheral (gastrointestinal and liver level) 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.

Key words: Ayahuasca, DMT, beta-carbolines, cardiovascular effects, pharmacokinetics, subjective effects

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