Fast and Slow Metabolizers ofHoasca

Harmine, a main alkaloid in ayahuasca (hoasca), inhibits monoamine oxidase-A and the cytochrome P450 isozyme 2D6, which metabolizes harmine. CYP 2D6 has genetic variations that may cause different effects among users. In 14 experienced male members of the União do Vegetal who received a standardized dose of hoasca, two subgroups of CYP 2D6 phenotypes—fast and slow metabolizers of harmine—were identified. In their religious practice, the presiding mestre individually adjusts the hoasca dose to compensate for metabolic differences and variations in alkaloid content.

Study at a glance

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.