A single dose of dimethyltryptamine (DMT), a psychedelic compound, produced a significant reduction in depressive symptoms in adults with major depressive disorder (MDD), according to a phase IIa clinical trial published Wednesday in Nature Medicine.
The study, a randomized, placebo-controlled trial, involved 34 participants with moderate-to-severe MDD who had previously not responded adequately to conventional treatments. Researchers found that those receiving DMT, administered intravenously alongside psychotherapeutic support, experienced a greater reduction in depression scores compared to those receiving a placebo.
MDD affects millions globally and is a leading cause of disability, yet many patients do not achieve full remission with existing therapies like selective serotonin reuptake inhibitors (SSRIs), which can also carry unwanted side effects. The findings suggest a potential new avenue for treatment, though researchers caution that further investigation is needed.
Participants in the trial received either 21.5 mg of DMT fumarate or a placebo, infused over 10 minutes. The primary measure of effectiveness was the change in Montgomery–Åsberg Depression Rating Scale (MADRS) scores at two weeks post-treatment. The DMT group showed a mean reduction in MADRS scores that was significantly greater than the placebo group (mean difference = −7.35; 95% CI = −13.62 to −1.08; P = 0.023).
Improvements were observed as early as one week after the DMT infusion. Even as an open-label phase of the trial offered all participants a second DMT dose, researchers noted that the most substantial clinical improvements occurred within two weeks of the initial dose, and there was no significant difference in outcomes between those receiving one versus two doses. This suggests the rapid onset of effect may be a key characteristic of DMT as a potential antidepressant.
The trial also assessed response rates – defined as a 50% or greater reduction in MADRS scores – and remission rates – defined as a MADRS score of 10 or less. At two weeks, 35% of participants in the DMT group achieved a response, compared to 12% in the placebo group. Remission rates were 29% in the DMT group and 12% in the placebo group. Researchers emphasized these estimates should be interpreted cautiously due to the small sample size.
The treatment was generally well-tolerated, with most adverse events being mild to moderate. Common side effects included injection site pain, anxiety, insomnia, headache, and restlessness. No serious adverse events or deaths were reported. Transient increases in heart rate and blood pressure were observed immediately following the DMT infusion, but clinical evaluations revealed no significant abnormalities.
DMT differs from other psychedelic therapies, such as those utilizing psilocybin – a compound found in magic mushrooms – in its shorter duration of effect. Psilocybin’s effects typically last for several hours, requiring extended therapeutic sessions. DMT, in contrast, produces a brief period of subjective psychedelic effects lasting around 30 minutes when administered intravenously, potentially making it more practical for clinical implementation, according to researchers.
The study’s authors acknowledge limitations, including the small sample size and the predominantly White participant population, which may limit the generalizability of the findings. They also noted the possibility of functional unblinding due to the pronounced subjective effects of DMT. Further research, including larger, longer-term studies comparing DMT to existing treatments, is needed to confirm these findings and evaluate the long-term safety and efficacy of DMT for MDD.
ClinicalTrials.gov registration: NCT04673383.
