Short-acting psychedelic DMT shows promise as a rapid treatment for major depressive disorder

A recent study published in Nature Medicine suggests that a brief psychedelic experience combined with talk therapy can rapidly and safely reduce symptoms of severe depression. The findings indicate that a single dose of a fast-acting psychedelic compound, administered intravenously, provides sustained relief for up to three months. This research offers early evidence for a mental health treatment that requires much less time in a clinic than other psychedelic therapies.

Dimethyltryptamine, commonly known as DMT, is a naturally occurring compound that produces intense but short-lived psychedelic effects. It works by interacting with the serotonin system in the brain, which plays a major role in regulating mood and processing emotions. While other psychedelics like psilocybin have shown promise for treating mood disorders, their effects tend to last four to six hours. This extended duration requires a full day of medical supervision, making the treatment expensive and difficult to scale for widespread use.

When given directly into a vein, the psychedelic effects of DMT last only twenty to thirty minutes. The scientists behind the new study wanted to find out if this brief window of altered consciousness, paired with dedicated psychological support, could meaningfully reduce depressive symptoms. Finding a faster-acting alternative could make psychedelic-assisted therapy more practical and accessible for people who do not respond to standard treatments.

“Major depressive disorder remains one of the leading causes of disability worldwide, and a substantial proportion of patients do not respond adequately to existing treatments,” said study author Tommaso Barba of Imperial College London.

“Psychedelics, particularly psilocybin, have shown real promise as antidepressants, but a key practical limitation is that psilocybin sessions typically require four to six hours of therapeutic supervision, making them costly and difficult to scale. DMT produces a psychedelic experience lasting only around 20 to 30 minutes when administered intravenously, and we wanted to find out whether this shorter experience could be equally clinically meaningful.”

The clinical trial included 34 adults diagnosed with moderate to severe major depressive disorder. All participants had previously tried at least two different treatments, such as traditional antidepressant medications or talk therapy, without success. The researchers designed a two-part study to test the safety and effectiveness of the drug. In the first phase, participants were randomly assigned to receive either a 21.5 milligram dose of DMT or a placebo, which is an inactive substance used for comparison.

Neither the participants nor the staff knew which substance was being administered during this initial stage. The treatment took place in a softly lit room designed to help participants feel calm. Participants wore eyeshades and listened to an ambient music playlist specifically chosen to match the trajectory of the drug experience. The drug or placebo was given as a ten-minute intravenous infusion.

Two trained therapists stayed in the room the entire time to provide quiet support, and a psychiatrist was present at the facility. Psychological support was a core component of the intervention rather than an optional addition. The day before the dosing session, participants spent ninety minutes with their therapists to prepare for the experience. Following the dosing session, participants completed several integration sessions where therapists helped them process any emotional or mystical experiences they had and apply those insights to their daily lives.

Two weeks after the first dose, the researchers measured depression severity using a standard clinical questionnaire called the Montgomery-Åsberg Depression Rating Scale. The scientists found that participants who received DMT experienced a significantly greater drop in their depression scores compared to those who received the placebo. Specifically, the DMT group scored an average of 7.35 points lower on the depression scale than the placebo group. These improvements happened rapidly, with notable reductions in symptoms appearing just one week after the treatment.

Two weeks after the initial blinded phase, the trial entered an open-label stage where all participants were offered a dose of DMT. This meant the original placebo group received their first active dose, while the original DMT group received a second active dose. Following this stage, the scientists monitored the participants for up to three months. The researchers found that the reduction in depressive symptoms was sustained throughout this follow-up period.

“A single intravenous dose of DMT, combined with psychological support from trained therapists, produced a significant and rapid reduction in depressive symptoms compared to placebo, with effects sustained for up to three months,” Barba told PsyPost. “It is important to emphasize that this was not simply a psychedelic experience: the therapeutic support provided before, during, and after the session was an integral part of the treatment, not an add-on.”

Interestingly, the data suggests that a single dose of DMT might be superior to two doses. Participants who received two doses of the drug did not show greater improvements than those who received only one dose. In fact, the group that received just a single dose during the open-label phase showed slightly better mental health scores at the three-month mark.

“One hypothesis is that participants in that group had a longer preparatory period before receiving the active compound, which may have led to better psychological readiness and a stronger or more durable response,” Barba said. “We are cautious about over-interpreting this given the small sample size, but it is an interesting signal worth investigating further.”

The treatment was generally well-tolerated by the participants. The most common side effects included pain at the injection site, nausea, and brief feelings of anxiety during the onset of the drug. These side effects were mild to moderate and typically went away before the end of the clinic visit. There were no serious adverse events, and the treatment did not increase suicidal thoughts or behaviors.

“The magnitude of the antidepressant effect we observed is comparable to what has been reported in psilocybin trials, which is striking given that the DMT experience lasts roughly 20 to 30 minutes compared to the four to six hours typically required with psilocybin,” Barba explained. “If these results are replicated in larger studies, it raises the exciting possibility that a shorter psychedelic experience could be as effective as a much longer one, with significant implications for the accessibility and cost of psychedelic-assisted therapy.”

Despite the promising outcomes, the study has some limitations that readers should keep in mind. The sample size was quite small, and the group of participants lacked ethnic diversity, which makes it difficult to know if the results apply to the broader population. Additionally, because the psychedelic effects of DMT are so obvious, participants likely knew whether they received the active drug or the placebo. This awareness can create expectations that influence how a person reports their symptoms.

“It would be a mistake to view this as evidence that DMT alone is an antidepressant,” Barba told PsyPost. “The therapeutic framework surrounding the dosing session was a core component of the treatment, not a backdrop. We also want to be clear that this was a small phase IIa trial, and the results need to be replicated in larger, more diverse populations before firm conclusions can be drawn.”

Several scientists involved in the study were employed by or held shares in Small Pharma and Cybin, the companies that sponsored the trial and provided the drug. Other members of the research team serve as paid advisors for various pharmaceutical and psychedelic research companies.

Moving forward, the scientists plan to conduct larger clinical trials using a modified version of DMT called HPL004. These future studies will aim to confirm the safety and effectiveness of the treatment in a larger, more diverse group of patients suffering from anxiety and depression. The researchers also hope to study the exact role of the therapeutic support component to better understand which patients are most likely to benefit from this fast-acting intervention.

“This promising trial offers a welcome glimmer of hope in the fight against depression, suggesting that DMT — similar to other psychedelic compounds — may bring a rapid reduction in symptoms within just a week, alongside clear improvements in response and remission rates that in many cases lasted for months,” said Liliana Galindo, affiliate assistant professor at the University of Cambridge, who was not involved in the study, in a statement to the Science Media Centre.

“The treatment was well tolerated, with no serious safety concerns linked to the drug, and because its effects are so short in duration, it could offer a more practical and time-efficient option than other therapies. While the study was small and further research is needed, the findings highlight the potential of a valuable new treatment for people who have not found relief through existing options.”

The study, “A short-acting psychedelic intervention for major depressive disorder: a phase IIa randomized placebo-controlled trial,” was authored by David Erritzoe, Tommaso Barba, Tiffanie Benway, Zelah Joel, Meghan Good, Marie Layzell, Michelle Baker Jones, Graham Campbell, Ashleigh Murphy-Beiner, Peter Rands, Malcolm Boyce, Helen Topping, Brandon Weiss, Christopher Timmermann, David Nutt, Robin Carhart-Harris, Carol Routledge, and Ellen James.