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

Marcelo Falchi-Carvalho, Handersson Barros, Raynara Bolcont, Sophie Laborde, Isabel Wießner, Sérgio Ruschi Bergamachi Silva, Daniel Montanini, D. Barbosa, Ewerton Teixeira, Rodrigo Florence-Vilela, Raíssa Nóbrega de Almeida, Rosana K. A. de Macedo, Flávia Arichelle, Érica J. Pantrigo, Emerson Arcoverde, Nicole Leite Galvão‐coelho, Dráulio Barros de Araújo, Fernanda Palhano-Fontes

medRxiv January 4, 2024 preprint DOI: 10.1101/2024.01.03.23300610 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Open-label, fixed-order, dose-escalation study (Phase 2a clinical trial)
Sample size 6
Population Patients with treatment-resistant depression
Intervention Vaporized DMT
Dose 15 mg then 60 mg
Duration Single-day session, follow-up to one month
Topics Anxiety Depression 5-MeO-DMT DMT
Keywords Antidepressant Depression economics Rating scale Clinical trial
Citations 5
Registration NCT06094907
Key findings Vaporized DMT produced rapid and sustained antidepressant effects in treatment-resistant depression, with 83% of patients responding by day seven and 67% maintaining response at one month.

Abstract

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 Trial registration Clinicaltrials.gov NCT06094907

Comparable studies

Other non-randomized and open-label trials on DMT for depression, most cited first.

Study Year Design Participants
Exploratory study of the dose-related safety, tolerability, and efficacy of dimethyltryptamine (DMT) in healthy volunteers and major depressive disorder. Treatment-resistant individuals with major depressive disorder (MDD) and healthy controls 2022 Open-label, fixed-order, dose-escalation exploratory phase 1 study n = 10
A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression Adult patients with treatment-resistant depression 2023 Phase 1/2 clinical trial n = 16
Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: a phase 2a clinical trial in treatment-resistant depression. Patients with treatment-resistant depression 2025 Open-label trial n = 14
The Antidepressant Effects of Vaporized N,N-Dimethyltryptamine: An Open-Label Pilot Trial in Treatment-Resistant Depression. Patients with treatment-resistant depression 2025 Open-label clinical trial n = 6
Beyond symptom reduction: DMT improves anxiety, life satisfaction, and quality of life in healthy volunteers and patients with depression Healthy individuals and patients with treatment-resistant depression 2026 Open-label clinical trial n = 41

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