A small clinical trial has found that a single dose of the psychedelic drug dimethyltryptamine (DMT) led to rapid and sustained reductions in depression symptoms when combined with therapy. Participants experienced improvements lasting up to six months, with mild side effects reported. The study highlights potential benefits of short-acting psychedelics for treatment-resistant depression.
Researchers at Imperial College London conducted a trial involving 34 individuals with moderate to severe depression lasting an average of 10 years, who had not responded to at least two prior conventional treatments including medications or psychotherapy.
In the study, half the participants received a 21.5-microgram intravenous dose of DMT over 10 minutes, alongside psychotherapeutic support, while the other half got a placebo infusion. Depression severity was assessed using a standard questionnaire before the trial. Two weeks after treatment, the DMT group's scores dropped by an average of 7.4 points more than the placebo group. These improvements held steady for three months and persisted up to six months for some participants.
A follow-up phase allowed all participants to receive DMT with therapy, but it did not yield significant additional benefits beyond the initial dose, indicating one session may suffice for lasting effects.
Side effects were generally mild, including temporary anxiety, nausea, and infusion-site pain. "We’ve shown that a single DMT experience, lasting only around 25 minutes, can be safe, well-tolerated and associated with meaningful improvements in depression that appear to persist beyond the acute psychedelic state," said lead researcher David Erritzoe. He noted the results resemble those from trials of longer-acting psychedelics like psilocybin and could lower treatment costs due to the brief duration.
The study acknowledged limitations, such as participants likely identifying their treatment due to DMT's distinct effects, which might influence outcomes through expectations. Greater intensity of mystical experiences—such as feelings of unity, emotional shifts, and altered perceptions of time and space—correlated with better therapeutic results, according to team member Tommaso Barba.
While the exact mechanisms remain unclear, prior research suggests DMT may open a window for brain neuroplasticity or reduce inflammation linked to mental health issues. Psychedelics researcher Rick Strassman praised the findings but urged caution, emphasizing DMT's potential for disorientation and the need for thorough preparation and monitoring.
The trial's outcomes could inform further development of DMT variants, such as Helus Pharma's HLP004 for anxiety, and related compounds like 5-MeO-DMT, which shows promise for depression treatment with expedited U.S. approval possible from AtaiBeckley.
The study was published in Nature Medicine (DOI: 10.1038/s41591-025-04154-z).
