The Antidepressant Effects of Vaporized N,N-Dimethyltryptamine: An Open-Label Pilot Trial in Treatment-Resistant...

N,N-Dimethyltryptamine (DMT), a naturally occurring psychedelic tryptamine contained in the indigenous ayahuasca brew, has shown antidepressant effects. This open-label clinical trial investigates for the first time the efficacy of vaporized DMT in treatment-resistant depression (TRD).

Six TRD patients participated in an open-label, fixed-order, dose-escalation study, receiving a lower (15 mg) and then a higher (60 mg) dose of vaporized DMT in a single-day session. Depression severity was assessed using the Montgomery-Asberg depression rating scale (MADRS) and the Patient Health Questionnaire-9 (PHQ-9) up to one month post-dosing.

Significant reductions in MADRS and PHQ-9 scores were noted from Day 1 to Month 1 (M1). The mean MADRS score variation from baseline to Day 7 (D7) was -22 points and -17 points at M1. PHQ-9 scores also showed significant decreases, mirroring the MADRS results. By D7, 83.33% of patients responded to treatment, with 66.67% achieving remission. At M1, 66.67% maintained response, and 50% maintained remission.

The rapid onset and sustained antidepressant effects of vaporized DMT align with the paradigm of rapid-acting antidepressants to be used in the scope of interventional psychiatry. The noninvasive route and short-acting nature of DMT offer practical advantages, potentially enhancing accessibility to psychedelic treatments.Clinical Trial Registration: Clinicaltrials.gov NCT06094907.