A recent clinical trial has found that a short-acting psychedelic, dimethyltryptamine (DMT), may help reduce symptoms of major depressive disorder (MDD). The study, published in Nature Medicine, involved adults diagnosed with moderate-to-severe MDD who had not responded to at least two previous treatments.
The research used a two-stage, randomized, placebo-controlled phase IIa design. In the first stage, participants received either DMT or a placebo without knowing which they were given. In the second stage, those who initially received a placebo were given DMT, while those who already had DMT received a second dose. All participants also received structured psychological support before and after dosing.
The main goal was to measure changes in depression severity using the Montgomery–Åsberg Depression Rating Scale (MADRS) two weeks after the first dose. Secondary outcomes included additional MADRS assessments up to 12 weeks after the second dose. Adverse events and safety measures such as heart rate and blood pressure were closely monitored.
According to the study’s findings, “A single 21.5 mg dose of DMT, administered with psychological support, resulted in rapid and significant reductions in depressive symptoms that persisted for up to three months in adults with MDD within the constraints of a small, carefully screened phase IIa study population. The treatment was safe and well-tolerated during the short follow-up period. Larger, longer studies, including comparisons with current therapies, are needed to further evaluate the safety, efficacy, durability of response, and cost-effectiveness of DMT for the treatment of MDD.”
Most participants experienced some side effects such as injection site pain or anxiety; these were generally mild or moderate. No serious adverse events or deaths occurred during the trial.
Researchers noted that most improvements happened within two weeks after receiving DMT. However, they cautioned that because only 34 people participated—most of whom identified as White—the results should be interpreted carefully and may not apply broadly.
Exploratory analyses suggested that how intense participants’ psychedelic experiences were might have influenced their antidepressant response.
The authors emphasize that more extensive research is needed to determine whether this approach can be widely recommended for treating depression.
