Inhaled DMT produces rapid and lasting antidepressant effects in treatment-resistant depression

A new study published in Neuropsychopharmacology has found that inhaled N,N-dimethyltryptamine (DMT), a fast-acting psychedelic compound, produced rapid and sustained antidepressant effects in people with treatment-resistant depression. Participants reported major reductions in depression and suicidal thoughts within a day of dosing, with benefits lasting up to three months. The therapy was safe, well-tolerated, and may offer a more accessible alternative to existing treatments.

DMT is a naturally occurring psychedelic compound found in certain plants and also produced in small amounts in the human body. It is best known as the main psychoactive ingredient in the Amazonian brew ayahuasca, but unlike ayahuasca, which requires co-administration of substances that prolong its effects, vaporized DMT acts quickly and clears the system within about 20 minutes. Because of its short duration and inhalation delivery, DMT has attracted interest as a potentially more scalable and less disruptive option for psychedelic therapy. The researchers aimed to investigate whether this compound could offer fast, lasting relief for people with depression who have not responded to traditional treatments.

“My team and I have been studying psychedelics, especially ayahuasca and DMT, for almost 20 years now,” said study author Draulio Barros de Araujo, a professor of neuroscience at the Brain Institute at Federal University of Rio Grande do Norte and director of the Center for Advanced Medical Psychedelics.

“What caught our attention with vaporized DMT is how it offers such a deep and intense psychedelic experience in a very short window of time. We were curious to see whether such a brief intervention, when supported properly, could still make a meaningful difference for people struggling with treatment-resistant depression.”

The study focused on individuals with treatment-resistant depression—a severe form of depression that does not improve after trying at least two different antidepressant medications. Fourteen adults were recruited through online ads, clinician referrals, and word-of-mouth. All met criteria for moderate to severe depression and had failed to respond to multiple prior medications. Participants received two doses of inhaled DMT in a controlled hospital setting: a lower dose of 15 milligrams followed by a higher dose of 60 milligrams about 90 minutes later. Both sessions occurred on the same day and were accompanied by preparation and integration support from trained clinicians.

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Participants inhaled DMT using a medical-grade vaporizer. During the experience, they lay back in a quiet room with dim lighting and calming music while being monitored by a psychiatrist, psychologist, and nurse. The team measured participants’ vital signs, mood, and subjective experience before, during, and after the sessions. Clinical assessments took place immediately after dosing, then at 1 day, 1 week, 2 weeks, 1 month, and 3 months later.

The researchers found that depression symptoms, measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), dropped significantly within 24 hours of treatment. On average, scores fell by 21 points—enough to shift many patients from a range of severe depression to mild or even minimal symptoms. About 79% of participants responded to the treatment by day 1, and 71% achieved full remission. By day 7, the response rate rose to nearly 86%, and more than half of participants remained in remission. Even after three months, 57% still showed a meaningful response and 36% remained in remission, despite receiving no further DMT.

“One of the most surprising aspects was just how consistently strong the clinical response was, even though the DMT experience itself only lasts about 10 to 20 minutes,” De Araujo told PsyPost. “Many participants not only reported emotional breakthroughs during the session, but also experienced lasting changes in mood and outlook from just a single dose. That’s not something we typically see with most psychiatric interventions.”

In addition to easing depressive symptoms, inhaled DMT also sharply reduced suicidal thoughts. Nearly 90% of participants had suicidal ideation at the start of the study, with almost half considered to be at severe risk. One day after treatment, no participants showed severe suicidal ideation. Improvements in suicidality were maintained in most participants through the 3-month follow-up. Notably, the reduction in suicidal thoughts closely tracked with improvements in mood, suggesting that the antisuicidal effect was related to the overall antidepressant impact.

Subjective reports indicated that the DMT experience was intense but generally positive. Participants described vivid imagery, altered perception, and insightfulness, with most rating the experience as pleasant. Physiological measurements showed temporary increases in blood pressure and heart rate shortly after dosing, similar to what might occur during moderate exercise, but no serious adverse events were reported. The most common side effects were throat irritation and coughing from inhalation, which resolved quickly. Headaches and mild discomfort were reported by some participants the following day.

Interestingly, the intensity of the psychedelic experience did not predict treatment outcome. While some participants had mystical or highly visual experiences, the researchers found no strong statistical links between specific features of the trip and clinical improvements. This suggests that the therapeutic effects of DMT might not depend on achieving a particular type of altered state. However, one measure—complex visual imagery—did show a trend toward association with better outcomes, echoing past research on psychedelics like ayahuasca and psilocybin.

One of the most promising aspects of this treatment is its practicality. Unlike longer-acting psychedelics like psilocybin or LSD, which require several hours for each session, vaporized DMT produces its effects in about 20 minutes. The entire protocol—including screening, preparation, dosing, and integration—can be completed in a single day. This has important implications for making psychedelic-assisted therapy more affordable and scalable, especially in public health systems with limited resources.

“The main takeaway is that even an ultra-short psychedelic experience, when delivered in a safe and supportive setting, can lead to rapid and sustained improvements in depression,” De Araujo said. “Perhaps most importantly, we saw a significant reduction in suicidal ideation in many participants within 24 hours, and those effects were still present months later. This suggests that DMT-assisted therapy might offer fast-acting relief, which could be especially valuable in urgent clinical situations.”

While these results are encouraging, the study has limitations. It was open-label, meaning both participants and researchers knew they were receiving DMT, which raises the possibility of placebo effects. The sample size was small, and the findings need to be confirmed in larger randomized controlled trials. In addition, the researchers did not collect pharmacokinetic data to measure how much DMT was actually absorbed, which limits conclusions about dose-response relationships. Some participants had minor fluctuations in symptoms over time, and one experienced a relapse in suicidality, underscoring the need for follow-up care.

“This was a Phase 2a open-label study, without a placebo group, and the number of participants was small,” De Araujo noted. “We have to be cautious in how we interpret the results.”

Future studies will need to compare DMT directly with placebo or other treatments, test repeated dosing regimens, and examine how integration sessions contribute to long-term outcomes. Better understanding how individual differences—such as prior psychedelic use, expectations, or co-occurring medication—affect results will also help tailor treatments. Monitoring for rare but serious side effects, including cardiovascular changes, will be essential as researchers scale up trials.

“From the beginning, our goal has been to develop a model of psychedelic-assisted therapy that fits within clinical, ethical, and economic boundaries,” De Araujo explained. “We believe that treatments that are overly long or expensive will face serious obstacles when it comes to integration into health systems, especially in countries like Brazil, where resources are limited and access is a real concern. In that sense, the vaporized DMT protocol we designed seems to strike a promising balance: it’s efficient, potentially scalable, and still therapeutically meaningful. Going forward, we aim to refine this model and test it in larger, controlled trials, always with a focus on safety, accessibility, and real-world feasibility.”

“This work is part of a larger movement, one that’s challenging old assumptions and inviting us to reimagine mental health care through the lens of altered states of consciousness. Psychedelics are not a magic bullet, but they can offer powerful tools when approached with scientific rigor, cultural sensitivity, and genuine care for the human experience. It’s been incredibly meaningful to witness how these experiences can reconnect people with themselves, and sometimes even bring hope back into view.”

The study, “Rapid and sustained antidepressant effects of vaporized N,N-dimethyltryptamine: A phase 2a clinical trial in treatment-resistant depression,” was authored by 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, and Draulio B. Araujo.