European journal of drug metabolism and pharmacokinetics
May 1, 2023
Meghan Good, Zelah Joel, Tiffanie Benway et al.
54 citations
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.
Frontiers in psychiatry
January 1, 2023
Ellen James, David Erritzøe, Tiffanie Benway et al.
16 citations
A phase 1 trial tested escalating intravenous doses of the psychedelic DMT (SPL026) in healthy volunteers who had never used psychedelics, to find a safe, tolerable dose for a future trial in people with major depressive disorder. Participants were randomly assigned to placebo or one of four doses (9, 12, 17, or 21.5 mg). The drug was well tolerated with no serious adverse events. Higher blood levels of DMT correlated with stronger ratings of mystical experience, ego dissolution, and intensity, though these trends need confirmation in larger studies. Based on safety and pharmacodynamic results, 21.5 mg given as a two-phase infusion was chosen for the patient trial.
ACS medicinal chemistry letters
September 14, 2023
Marie Layzell, Peter Rands, Meghan Good et al.
6 citations
A deuterated analogue of DMT, called D2-DMT, has a longer half-life and slower clearance in liver cell fractions than standard DMT while maintaining a similar receptor binding profile, making it a promising candidate for extended treatment of major depressive disorder.
Nat Med
February 16, 2026
David Erritzøe, Tommaso Barba, Tiffanie Benway et al.
4 citations
A single 21.5-mg intravenous dose of the psychedelic DMT, given with psychotherapeutic support, produced a rapid and significant reduction in depressive symptoms in adults with moderate-to-severe major depressive disorder. In a double-blind, placebo-controlled trial with 34 participants, those receiving DMT showed a greater decrease in depression scores at two weeks compared to placebo. Antidepressant effects persisted up to three months in an open-label phase. Adverse events were mostly mild to moderate, and no serious adverse events occurred.
Meghan Good, Tiffanie Benway, Zelah Joel et al.
4 citations
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.