Topic starter
There is a new scientific article which investigates whether short-acting psychedelic treatment with DMT can help people with moderate to severe depression.
In it, we discuss:
The researchers conducted a phase 2a, double-blind, randomised, placebo-controlled study in adults with major depressive disorder. Participants received one intravenous infusion of 21.5 mg DMT or placebo over 10 minutes, combined with psychotherapeutic support. This was followed by a two-week assessment, after which all participants could also receive DMT in an open-label phase.
The real focus of this article is on whether one relatively short-acting psychedelic session can already produce an antidepressant effect within a short period of time. This is interesting because DMT works out much faster than, say, psilocybin, creating a treatment window that is much shorter but may still remain therapeutically relevant.
The outcomes were positive. After two weeks, the DMT group showed a significantly greater decrease on the MADRS depression scale than the placebo group. The mean difference between the two groups was 7.35 points in favour of DMT. According to the authors, this indicates a rapid and clinically relevant decrease in depressive symptoms after one session with DMT and psychotherapeutic counselling.
The authors also describe that antidepressant effects persisted for up to three months in the open-label phase. In doing so, they found no significant difference between participants who eventually received one DMT dose and those who received two doses. This suggests that one dose in this small study already gave much of the observed effect, although this is not yet definitive evidence for the optimal dosage or treatment strategy.
Importantly, however, this was a small phase 2a study with 34 randomised participants. In addition, all participants received psychotherapeutic support, so the effect cannot be attributed purely to DMT alone. The authors do report that the treatment was generally well tolerated. The most commonly reported side effects were IV pain, nausea and transient anxiety. Serious side effects were not seen.
In one sentence, this article shows that one supervised DMT infusion in a small placebo-controlled study rapidly and significantly reduced depressive symptoms, with effects that remained visible in the follow-up phase for up to three months.
Spoiler
New article description
Abstract
Major depressive disorder (MDD) is a leading cause of disability worldwide, yet many patients have inadequate responses to current treatments. Dimethyltryptamine (DMT), a serotonergic psychedelic with rapid onset and short duration, shows promise as a potential antidepressant (AD), although clinical evidence in MDD remains limited.
We conducted a phase IIa, double-blind, placebo-controlled, randomised clinical trial to evaluate the efficacy and safety of intravenous DMT (SPL026; DMT fumarate) in adults with moderate-to-severe MDD. Participants received a single 21.5-mg dose of DMT or placebo infused over 10 min, along with supportive psychotherapeutic support, followed by a 2-week assessment. A subsequent open-label phase offered all participants a second DMT dose.
The primary outcome was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) at 2 weeks. Secondary outcomes included response (≥50% reduction in MADRS score) and remission (MADRS ≤ 10). A total of 34 participants were randomised, 17 to placebo-active and 17 to active-active. At 2 weeks, the DMT group showed a significantly greater reduction in MADRS score than placebo (mean difference = -7.35; 95% CI = -13.62 to -1.08; P = 0.023).
In the open-label phase, AD effects persisted up to 3 months, with no significant differences between those who received one versus two doses. Adverse events were mostly mild to moderate, commonly infusion site pain, nausea and transient anxiety. No serious adverse events occurred. A single dose of DMT with psychotherapeutic support produced a rapid, significant reduction in depressive symptoms, sustained up to 3 months. The treatment was well-tolerated and safe.
Keywords: DMT; major depressive disorder; antidepressant; placebo-controlled trial; intravenous infusion; psychotherapeutic support; MADRS.
Posted : 18 March 2026 14:44