Development of a physiologically based pharmacokinetic model of N,N-dimethyltryptamine, harmine, and their interactions from ayahuasca in rats and humans.
Toxicological sciences : an official journal of the Society of Toxicology November 1, 2025 Naphat Wittayakarn, Yu-Mei Tan, Pattanachai Choomalaiwong et al.
Ayahuasca, a traditional Amazonian brew containing DMT from Psychotria viridis and harmine from Banisteriopsis caapi, produces psychoactive effects because harmine inhibits monoamine oxidase-A, preventing DMT's metabolism and increasing its systemic bioavailability. The brew shows potential therapeutic benefits for depression, anxiety, and substance use disorders. Researchers developed physiologically based pharmacokinetic (PBPK) models for DMT and harmine in rats and humans, accounting for multiple administration routes and harmine's inhibition of DMT metabolism in the liver and lungs. The models reasonably predicted plasma concentrations across dosing conditions. Simulations suggest that maintaining plasma concentration above a threshold may be more relevant for therapeutic effects than peak levels, offering a framework for safer dosing.