A single-day session of vaporized DMT, a psychedelic compound found in ayahuasca, rapidly reduced depression symptoms in six patients with treatment-resistant depression. Depression scores on two standard rating scales dropped substantially by day one and remained lower for one month. By day seven, 83% of patients responded to treatment and 67% achieved remission; at one month, 67% maintained response and 50% maintained remission. The non-invasive, short-acting nature of DMT may make psychedelic treatments more accessible in interventional psychiatry.
The biosynthetic pathway of the psychoactive compound N,N-dimethyltryptamine (DMT) involves two methylation steps of tryptamine, but the molecular details of the double methylation were previously unknown. Using computational modeling—molecular dynamics, density functional theory, and ONIOM QM:MM calculations—the authors show that the reaction follows an SN2 mechanism. The second methylation is the rate-limiting step, with an energy barrier 60 kJ·mol⁻¹ higher than the first, due to more repulsive non-covalent interactions in the second transition state. The findings provide geometric details about each reaction step and clarify the energetics of DMT biosynthesis.