Recent research published in natural medicine A brief psychedelic experience combined with talk therapy suggests that it can quickly and safely reduce symptoms of severe depression. The results of this study show that a single intravenous dose of a fast-acting psychedelic compound can provide sustained relief for up to three months. This study provides early evidence for a mental health treatment that can significantly reduce clinic time compared to other psychedelic treatments.
Dimethyltryptamine, commonly known as DMT, is a natural compound that produces strong but short-lasting psychedelic effects. It works by interacting with the serotonin system in the brain, which plays a key role in regulating mood and processing emotions. Other psychedelic drugs, such as psilocybin, have shown promise in treating mood disorders, but their effects tend to last four to six hours. This long-term treatment requires full-day physician supervision, making it expensive and difficult to scale up for widespread use.
When DMT is administered directly into a vein, the psychedelic effects last only 20 to 30 minutes. The scientists behind the new study wanted to know whether this brief period of altered consciousness, combined with dedicated psychological support, could meaningfully reduce symptoms of depression. Finding fast-acting alternatives could make psychedelic-assisted therapy more practical and accessible for people who don’t respond to standard treatments.
“Major depressive disorder remains one of the leading causes of disability worldwide, and a significant proportion of patients do not respond adequately to existing treatments,” said study author Tommaso Barba from Imperial College London.
“Psychedelics, and psilocybin in particular, have shown real promise as antidepressants, but important practical limitations are that psilocybin sessions typically require 4 to 6 hours of therapeutic supervision, making them expensive and difficult to scale up. DMT produces a psychedelic experience for only about 20 to 30 minutes when administered intravenously, and we wanted to know if this brief experience was similarly clinically meaningful.”
The clinical trial involved 34 adults diagnosed with moderate to severe major depressive disorder. All participants had previously tried at least two different treatments, including traditional antidepressants and talk therapy, without success. The researchers designed a two-part study to test the drug’s safety and effectiveness. In the first phase, participants were randomly assigned to receive either 21.5 milligrams of DMT or a placebo, an inert substance used for comparison.
Neither participants nor staff knew which substances were being administered at this early stage. Treatments took place in a soft-lit room designed to keep participants calm. Participants wore eyeshades and listened to a playlist of ambient music chosen specifically to match their drug experience trajectory. Drug or placebo was administered as a 10-minute intravenous infusion.
Two trained therapists were in the room at all times to provide silent support, and the facility also had a psychiatrist on-site. Psychological support was a core component of the intervention rather than an optional addition. The day before the administration session, participants spent 90 minutes with a therapist to prepare for the experience. After the administration session, participants completed several integration sessions in which the therapist helped them process the emotional or mystical experiences they had and apply those insights to their daily lives.
Two weeks after the first dose, researchers measured depression severity using a standard clinical questionnaire called the Montgomery-Asberg Depression Rating Scale. Scientists found that participants who received DMT experienced a significant reduction in depression scores compared to those who received a placebo. Specifically, the DMT group scored an average of 7.35 points lower on the depression scale than the placebo group. These improvements occurred rapidly, with a noticeable reduction in symptoms after just 1 week of treatment.
Two weeks after the initial blinding phase, the study entered an open-label phase in which all participants were offered administration of DMT. This means that the original placebo group received the first active dose and the original DMT group received the second active dose. Following this step, the scientists monitored the participants for up to three months. The researchers found that reductions in depressive symptoms were maintained during this follow-up period.
“A single intravenous dose of DMT combined with psychological support from a trained therapist significantly and rapidly reduced symptoms of depression compared to placebo, with effects lasting up to three months,” Barba told PsyPost. “It is important to emphasize that this was not just a psychedelic experience. The therapeutic support provided before, during and after the session was not an add-on but an integral part of the treatment.”
Interestingly, the data suggest that a single dose of DMT may be superior to two doses. Participants who received two doses of the drug did not show greater improvement than those who received only one dose. In fact, the group that received just one dose during the open-label phase had slightly better mental health scores after three months.
“One hypothesis is that because the participants in that group had a longer preparation period before receiving the active compound, they may have been more psychologically prepared and had a stronger and more sustained response,” Barba said. “We’re wary of overextending this given the small sample size, but it’s an interesting signal worth investigating further.”
The treatment was generally well accepted by participants. The most common side effects included pain at the injection site, nausea, and temporary anxiety when starting the drug. These side effects were mild to moderate and usually disappeared before the end of the visit. There were no serious adverse events, and the treatment did not increase suicidal thoughts or behavior.
“The magnitude of the antidepressant effects we observed are comparable to those reported in trials of psilocybin, which is surprising given that the DMT experience lasts approximately 20 to 30 minutes, compared to the 4 to 6 hours typically required with psilocybin,” Barba explained. “If these results are replicated in a larger study, they raise the intriguing possibility that shorter psychedelic experiences may be just as effective as longer psychedelic experiences, which could have a significant impact on the accessibility and cost of psychedelic-assisted therapy.”
Despite the promising results, this study has several limitations that readers should be aware of. The sample size was very small and the group of participants lacked ethnic diversity, making it difficult to know whether the results applied to the broader population. Furthermore, the psychedelic effects of DMT are so obvious that participants may have known whether they were given the active drug or a placebo. This perception can create expectations that influence how a person reports symptoms.
“It would be a mistake to see this as evidence that DMT is the only antidepressant,” Barba told Cypost. “The treatment framework surrounding the dosing sessions was a core element of the treatment, rather than a backdrop. We also want to be clear that this was a small Phase IIa trial, and the results need to be replicated in a larger and more diverse population before any firm conclusions can be drawn.”
Several scientists involved in the study were employed by or held stock in Small Pharma and Cybin, which sponsored the trial and provided the drug. Other members of the research team serve as paid advisors to various pharmaceutical and psychedelic research companies.
In the future, scientists plan to conduct large-scale clinical trials using a modified version of DMT called HPL004. These future studies aim to confirm the safety and effectiveness of the treatment in a larger and more diverse group of patients suffering from anxiety and depression. The researchers also hope to study the precise role of treatment support elements to better understand which patients are most likely to benefit from this fast-acting intervention.
“This promising trial provides a welcome ray of hope in the fight against depression, suggesting that, like other psychedelic compounds, DMT may produce rapid symptom relief within just a week, with clear improvements in response and remission rates that often lasted for months,” Assistant Professor Liliana Galindo from the University of Cambridge, who was not involved in the study, said in a statement to the Science Media Center.
“This treatment is well-tolerated, there are no significant safety concerns associated with the drug, and the very short duration of action may make it a more practical and time-efficient option than other treatments. Although the study is small and more research is needed, our findings highlight a potentially valuable new treatment for people whose symptoms have not been relieved by existing options.”
The study, “Short-acting psychedelic interventions for major depressive disorder: A phase IIa randomized placebo-controlled trial,” was authored by David Elizzo, Tommaso Barba, Tiffany Benway, Zella Joel, Megan Good, Marie Raisel, Michelle Baker-Jones, Graham Campbell, Ashley Murphy-Beyner, Peter Landes, Malcolm Boyce, Helen Topping, and Brandon. Weiss, Christopher Timmerman, David Nutt, Robin Carhart-Harris, Carol Routledge, Ellen James.
