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 : official publication of the American College of Neuropsychopharmacology May 1, 2025 DOI: 10.1038/s41386-025-02091-6 (opens in new tab)
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.
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Inhaled DMT produced rapid and sustained antidepressant effects, with an average 21.14-point reduction on the MADRS by day 7 and high response and remission rates.
Synthesized
Comparable studies
Other non-randomized and open-label trials on DMT for depression, most cited first.