Ayahuasca contains DMT and harmine, but their interactions are not fully understood. In a single-blind, randomized, two-arm, factorial dose-finding study with 16 healthy participants, each received six dose combinations of DMT (0-120 mg) and harmine (0-180 mg) via a transmucosal delivery system. All combinations produced dose-dependent subjective effects lasting 4-5 hours, with peak DMT and harmine levels reaching 33 ng/mL and 49 ng/mL, respectively. The interaction was bidirectional: harmine reduced DMT metabolism, while DMT altered harmine pharmacokinetics. The formulation had a favorable safety profile, supporting further testing for affective disorders.
The psychedelic compound DMT is often taken with harmine, a monoamine oxidase inhibitor, as in ayahuasca, but how harmine alters DMT's effects was not well understood. In a study of 16 healthy adults, six combinations of buccal DMT (0-120 mg) and harmine (0-180 mg) were given. Harmine increased DMT's bioavailability and prolonged its absorption, leading to higher and more sustained blood levels. The intensity of subjective psychedelic effects rose with dose, and harmine potentiated these effects at higher DMT doses. A mathematical model captured these relationships and individual variability, offering a foundation for more personalized dosing in psychedelic therapy.