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The antidepressant effects of vaporized N,N-Dimethyltryptamine: a preliminary report in treatment-resistant depression

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Almeida, R., Araújo, D. B., Arcoverde, E., Arichelle, F., Barbosa, D. C., Barros, H., Bolcont, R., Falchi-Carvalho, M., Florence-Vilela, R., Galvão-Coelho, N. L., Laborde, S., Macedo, R. K. A., Montanini, D., Palhano-Fontes, F., Pantrigo, E. J., Silva, S. R. B., Teixeira, E., Wießner, I.

This open-label Phase IIa clinical trial (n=6) examines the efficacy of vaporized DMT in treating treatment-resistant depression (TRD). Patients experienced significant reductions in two depression scores (MADRS & PHQ-9), with 83% responding to treatment by day 7 and 66.67% achieving remission. The rapid onset and sustained antidepressant effects of vaporized DMT suggest its potential as a practical and accessible option in psychedelic treatments for depression within interventional psychiatry.

Abstract

Introduction N,N-Dimethyltryptamine (DMT), a naturally occurring psychedelic tryptamine contained in the indigenous ayahuasca brew has shown antidepressant effects. This Phase 2a clinical trial investigates for the first time the efficacy of isolated DMT in treatment-resistant depression (TRD).Methods 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.Results Significant reductions in MADRS and PHQ-9 scores were noted from Day 1 to M1. The mean MADRS score variation from baseline to 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.Discussion 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 non-invasive route and short-acting nature of DMT offer practical advantages, potentially enhancing accessibility to psychedelic treatments.