The antidepressant effects of vaporized N,N-Dimethyltryptamine: a preliminary report in treatment-resistant depression
This Phase 2a open‑label, dose‑escalation study in six patients with treatment‑resistant depression found that a single‑day session of vapourised N,N‑dimethyltryptamine produced rapid and sustained reductions in depressive symptoms (mean MADRS change −22 at Day 7 and −17 at one month), with 83.3% response and 66.7% remission at Day 7 and 66.7% response and 50% remission at one month. The authors highlight the non‑invasive, short‑acting delivery as a practical advantage that could improve accessibility of psychedelic-assisted interventional psychiatry.
Authors
- Fernanda Palhano-Fontes
- Draulio Araújo
- Nathalia Galvão-Coelho
Published
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. Clinical
Research Summary of 'The antidepressant effects of vaporized N,N-Dimethyltryptamine: a preliminary report in treatment-resistant depression'
Introduction
N,N-Dimethyltryptamine (DMT) is a naturally occurring psychedelic tryptamine that produces brief but intense alterations in consciousness when administered parenterally. The compound is a component of the traditional brew ayahuasca, in which monoamine oxidase inhibitors permit oral activity; clinical research on ayahuasca has suggested rapid antidepressant effects. Despite emerging evidence for psychedelic treatments in mood disorders, the effects of isolated, vaporized DMT in patients with treatment‑resistant depression (TRD) had not been tested in a Phase II clinical trial prior to this study. Falchi‑Carvalho and colleagues set out to evaluate the efficacy and tolerability of inhaled, isolated DMT in patients with TRD. The study aimed to examine whether a single-day, fixed-order, dose‑escalation administration of vaporized DMT produces rapid and sustained reductions in depressive symptoms, and to characterise acute subjective effects and safety in a therapeutic setting. This Phase 2a trial therefore probes an alternative, short‑acting route of administration that could have practical advantages over longer‑acting oral psychedelics.
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Study Details
- Study Typeindividual
- Journal
- Compounds
- Topics
- Authors
- APA Citation
Falchi-Carvalho, M., Barros, H., Bolcont, R., Laborde, S., Wießner, I., Silva, S. R. B., Montanini, D., Barbosa, D. C., Teixeira, E., Florence-Vilela, R., Almeida, R., de Macedo, R. K. A., Arichelle, F., Pantrigo, É. J., Arcoverde, E., Galvão-Coelho, N., Araujo, D. B., & Palhano-Fontes, F. (2024). The antidepressant effects of vaporized N,N-Dimethyltryptamine: a preliminary report in treatment-resistant depression. https://doi.org/10.1101/2024.01.03.23300610
References (8)
Papers cited by this study that are also in Blossom
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Falchi, M., Wießner, I., Silva, S. R. B. et al. · European Neuropsychopharmacology (2024)
Reckweg, J., Mason, N. L., van Leeuwen, C. et al. · Frontiers in Pharmacology (2021)
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Cited By (1)
Papers in Blossom that reference this study
Lima, G., Soares, C., Teixeira, M. et al. · Scientific Reports (2025)
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