DMT, a psychedelic compound being developed for major depressive disorder, is rapidly cleared from the body with a mean elimination half-life of 9 to 12 minutes. In vitro experiments showed that blocking monoamine oxidase A and certain cytochrome P450 enzymes (CYP2D6 and, to a lesser extent, CYP2C19) slowed DMT's clearance. The drug has low lipophilicity and low plasma protein binding, meaning a high proportion is available for distribution and metabolism, consistent with its very fast clinical pharmacokinetics. In a phase I trial, 24 healthy adults received single escalating intravenous infusions of DMT (9–21.5 mg freebase) over 10 minutes. All doses were safe and well tolerated, and peak plasma concentrations did not relate to body weight or BMI. These results support developing novel DMT infusion regimens for treating major depressive disorder.
DMT (N,N-dimethyltryptamine) is being developed as a treatment for major depressive disorder. In a phase I trial, 24 healthy adults received escalating intravenous doses of DMT fumarate (SPL026) that were safe and well-tolerated. DMT exposure increased proportionally with dose over the 9–21.5 mg range. Peak plasma concentration occurred at about 10 minutes, and the mean elimination half-life was 9–12 minutes. In vitro experiments showed that DMT is cleared by monoamine oxidase A (MAO-A) and modified by the enzymes CYP2D6 and CYP2C19. The unbound fraction of DMT in plasma was approximately 70%. These findings support the development of DMT infusion regimens for treating major depressive disorder.