Fast and Slow Metabolizers ofHoasca
Journal of Psychoactive Drugs – June 01, 2005
Source: OpenAlex
Summary
Harmine, a key alkaloid in ayahuasca, selectively inhibits the enzyme monoamine oxidase-A and the cytochrome P450 isozyme 2D6, crucial for its metabolism. In a study of 14 experienced male members of União do Vegetal, distinct phenotypes were observed: fast and slow metabolizers of harmine. The presiding mestre adjusts dosages to accommodate these metabolic differences, ensuring that each individual's experience is tailored. This traditional practice highlights the intersection of pharmacogenetics and cultural medicine in optimizing therapeutic effects.
Abstract
Harmine, a major alkaloid in ayahuasca (hoasca), is a selective and reversible inhibitor of the enzyme monoamine oxidase-A (MAO-A). It is also a selective inhibitor of the human cytochrome P450 isozyme 2D6 (CYP 2D6), which metabolizes harmine to a more hydrophilic derivative for eventual excretion. CYP 2D6 exhibits a wide range of polymorphisms in human populations, and variations in this enzymatic activity could account for differences in effects between individuals who use hoasca. This report broadly describes two subgroups of CYP 2D6 phenotypes--i.e., fast and slow metabolizers of harmine-in 14 experienced male members of the União do Vegetal (UDV) who received a standardized dosage of hoasca. To compensate for metabolic variations in their normal religious practice, the administered dose of hoasca is always determined by the presiding mestre, who is responsible for deciding the actual amount for each individual. This age-old method compensates for metabolic variations between individuals and variations in both the alkaloid profile and strength of the hoasca.