Vaporized DMT Shows Promise for Rapid and Sustained Relief in Treatment-Resistant Depression

A new phase 2a clinical trial brings hope to patients struggling with treatment-resistant depression (TRD) through an innovative approach: inhaled N,N-dimethyltryptamine (DMT).

In a landmark study published in Neuropsychopharmacology (2025), researchers led by Marcelo Falchi-Carvalho, Fernanda Palhano-Fontes, and colleagues from the Federal University of Rio Grande do Norte (Brazil) demonstrated that vaporized DMT provides rapid, significant, and lasting antidepressant effects in individuals with TRD.

Depression affects over 185 million people worldwide, with about a third classified as treatment-resistant, meaning they fail to respond to at least two antidepressants. Traditional medications typically take weeks to work and offer limited immediate help for suicidal ideation. This urgent therapeutic gap prompted scientists to explore faster-acting alternatives.

Why DMT?

DMT, a naturally occurring psychedelic found in ayahuasca, acts quickly — its psychedelic effects peak within 2–5 minutes and resolve within 20 minutes. Unlike ayahuasca, which requires monoamine oxidase inhibitors (MAOIs) and involves hours-long sessions, vaporized DMT bypasses these complications, offering a non-invasive, time-efficient, and pharmacologically safer option.

The Study: A New Frontier in Interventional Psychiatry

In this open-label, dose-escalation trial (NCT06094907), 14 patients with moderate-to-severe TRD inhaled two escalating doses of DMT (15 mg followed by 60 mg) in a supportive clinical environment. Results were striking:

• Rapid Effect: A significant reduction in depressive symptoms was observed within 24 hours.
• Sustained Relief: The antidepressant effect persisted for up to three months after a single day of treatment.
• High Response and Remission Rates:
  • 71% responded to treatment (≥50% reduction in depression scores) by day 7.
  • 14% achieved remission (minimal depressive symptoms) by day 7.
• Reduction in Suicidal Ideation: Severe suicidal thoughts vanished within a day and remained significantly lower throughout the follow-up.

Participants tolerated the treatment well, mainly reporting mild and transient side effects like throat discomfort or coughing during inhalation. Notably, the study noted no serious adverse events.

Psychedelic Experience

The psychedelic experience, although intense, was brief and well-tolerated. Participants often reported vivid imagery and emotional insight, but with minimal anxiety or cognitive disruption. The visual phenomena correlated with greater antidepressant improvements, highlighting the therapeutic relevance of these altered states.

Implications and Future Directions

This study suggests that vaporized DMT could offer a revolutionary option for treating depression:

• Short Treatment Sessions: Unlike psilocybin or ketamine therapies requiring hours of clinical supervision, DMT sessions last only 30–60 minutes.
• Scalability and Accessibility: DMT could be more easily integrated into public health settings due to lower costs and shorter clinical times.
• Compatibility with Antidepressants: Vaporized DMT does not require patients to discontinue existing antidepressant medications, enhancing safety and practicality.

The authors acknowledge that the study’s open-label design and small sample size call for further research. Ongoing and future placebo-controlled trials, larger sample sizes, and detailed pharmacokinetic studies are necessary to validate these findings fully.

Reference

Falchi-Carvalho, M., Palhano-Fontes, F., Wießner, I., Barros, H., Bolcont, R., Laborde, S., et al. (2025). Rapid and sustained antidepressant effects of vaporized N, N-dimethyltryptamine: a phase 2a clinical trial in treatment-resistant depression. Neuropsychopharmacology, 50, 895–903. https://doi.org/10.1038/s41386-025-02091-6

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