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Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: a phase 2a clinical trial in treatment-resistant depression.

Marcelo Falchi-Carvalho, Fernanda Palhano-Fontes, Isabel Wießner, Handersson Barros, Raynara Bolcont, Sophie Laborde, Sérgio Ruschi B Silva, Daniel Montanini, David C Barbosa, Ewerton Teixeira, Rodrigo Florence-Vilela, Raissa Almeida, Rosana K. A. de Macedo, Flávia Arichelle, Érica J. Pantrigo, José V Costa-Macedo, João Arthur da Cruz Nunes, Luiz Antonio de Araújo Costa Neto, Luis Fernando Nunes Ferreira, Luísa Dantas Corrêa, Romária Bárbara da Costa Bezerra, Emerson Arcoverde, Nicole Galvão-Coelho, Draulio B Araujo

Neuropsychopharmacology May 1, 2025 DOI: 10.1038/s41386-025-02091-6 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Open-label trial Peer reviewed
Sample size 14
Population Patients with treatment-resistant depression
Interventions N N-Dimethyltryptamine (DMT)
Dose 15 mg and 60 mg
Duration Single dosing session, with follow-up to 3 months
Topics 5-MeO-DMT Depression DMT
Keywords Mental health Depression treatment Psychedelic medicine Clinical research Therapeutic breakthroughs
Citations 35
Registration NCT06094907
Key findings Inhaled DMT produced rapid and sustained antidepressant effects in treatment-resistant depression, with an average 21.14-point reduction on the Montgomery-Asberg Depression Rating Scale by day 7 and high response and remission rates.

Abstract

Depression affects over 185 million people worldwide, with approximately one-third classified as treatment-resistant depression (TRD). Current treatments, such as oral antidepressants, often take around 3 weeks to become effective, with no immediate anti-suicidal benefits. The field urgently needs innovative therapies that provide rapid relief. Psychedelics like psilocybin and ayahuasca have shown promising antidepressant effects; however, their long duration (several hours) makes them costly and impractical for public health systems. N,N-Dimethyltryptamine (DMT), an endogenous psychedelic also found in ayahuasca, offers a viable alternative with a short duration of action (10-20 min) and non-invasive inhalation administration. Unlike ayahuasca, which contains monoamine oxidase inhibitors, vaporized DMT acts quickly and poses fewer pharmacological interaction risks. This open-label trial evaluated inhaled DMT for TRD for the first time, within the framework of interventional psychiatry. Fourteen patients (Nfemale = 6) participated in a fixed-order, dose-escalation study (15 mg and 60 mg). The treatment was safe, well-tolerated, and produced manageable psychedelic effects with no serious adverse events. A subpopulation using antidepressants showed similar safety outcomes. Results showed rapid and sustained antidepressant effects, with an average reduction of 21.14 points on the Montgomery-Asberg Depression Rating Scale by day 7 (p < 0.001). The response rate was 85.71%, and the remission rate was 57.14% 7 days post-administration, lasting up to 3 months. Suicidal ideation significantly decreased, with no severe ideation the day after dosing. Vaporized DMT offers a non-invasive, time-efficient, and cost-effective alternative to other psychedelics and traditional antidepressants, supporting its role in interventional psychiatry and public health. Clinicaltrials.gov NCT06094907.

In the evidence

This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.

  • State of the evidence: DMT for depression Supports

    Inhaled DMT (15 mg and 60 mg) was safe and produced a mean 21.14-point MADRS reduction by day 7 (p < 0.001) with an 85.71% response rate.

    Synthesized

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
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
The antidepressant effects of vaporized N,N-Dimethyltryptamine: a preliminary report in treatment-resistant depression Patients with treatment-resistant depression 2024 Open-label, fixed-order, dose-escalation study (Phase 2a 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

Citations in the library

Cited by 37

and 32 more in the library

Cites 39

and 34 more in the library

Related reading

Explore topics

5-MeO-DMT Depression DMT Ayahuasca Psilocybin Psychedelic-assisted therapy

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DMT for depression