This open-label fixed-order dose-escalation trial (n=14) evaluated inhaled DMT (15mg & 60mg) for treatment-resistant depression (TRD) for the first time. Results showed rapid and sustained antidepressant effects with a 21-point reduction on the Montgomery-Asberg Depression Rating Scale by day 7 (p<0.001), an 86% response rate, and a 57% remission rate lasting up to 3 months, with significant decreases in suicidal ideation (SI).
Abstract of Rapid and sustained antidepressant effects of vaporized DMT
“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.”
Authors: 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
Summary of Rapid and sustained antidepressant effects of vaporized DMT
Major Depressive Disorder (MDD) affects over 185 million people worldwide, with traditional antidepressants typically taking more than three weeks to show effects. This delay leaves patients vulnerable to persistent symptoms and increased suicide risk during the latency period. Approximately one-third of patients are classified as having Treatment-Resistant Depression (TRD), with response rates dropping significantly after each failed treatment attempt. This situation underscores an urgent need for novel, effective, and scalable therapeutic approaches that can be integrated into public health systems.
Falchi-Carvalho and colleagues note that while serotonergic psychedelics like psilocybin and ayahuasca have shown promising rapid antidepressant effects, their long duration of action (several hours) poses practical and economic challenges for widespread clinical use. DMT, an indole alkaloid found naturally in various species including humans, offers a potential alternative with its shorter duration of action. While DMT is rapidly metabolised when taken orally (unless combined with MAO inhibitors as in ayahuasca), parenteral administration might offer a more controlled and safer application in therapeutic contexts.
The researchers note that early studies of DMT in humans date back to the 1950s, with intramuscular administration followed by intravenous studies in the 1990s. These investigations revealed that DMT produces effects similar to other psychedelics but with a much quicker onset (2-5 minutes) and shorter duration (10-60 minutes). However, a non-invasive route might be safer and would simplify clinical use. The researchers previously conducted a Phase I study of inhaled DMT in healthy volunteers, finding it to be well-tolerated with mild and transient physiological effects.
Methods
Study Design and Participants
Find this paper
https://doi.org/10.1038/s41386-025-02091-6
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Cite this paper (APA)
Falchi-Carvalho, M., Palhano-Fontes, F., Wießner, I., Barros, H., Bolcont, R., Laborde, S., ... & B. Araujo, D. (2025). Rapid and sustained antidepressant effects of vaporized N, N-Dimethyltryptamine: A Phase 2a clinical trial in Treatment-Resistant Depression. Neuropsychopharmacology, 1-9.
Study details
Compounds studied
DMT
Topics studied
Treatment-Resistant Depression
Depression
Study characteristics
Original
Open-Label
Participants
14
Humans
Compound Details
The psychedelics given at which dose and how many times
DMT 15 - 60mg | 1x
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The antidepressant effects of vaporized N,N-Dimethyltryptamine: a preliminary report in treatment-resistant depressionThis 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.
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