RCT · 2026
A single IV dose of DMT lowered depression scores more than placebo in a 34-person trial
- Original title
- A short-acting psychedelic intervention for major depressive disorder: a phase IIa randomized placebo-controlled trial.
- Authors
- Erritzoe D, Barba T, Benway T, et al.
- Journal
- Nature medicine, 2026
- Molecules
- DMT
- Conditions
- Depression
- Participants
- 34
- Evidence grade
- Moderate
- Source
- Read the original paper
The question
Can a single intravenous dose of DMT, a short-acting psychedelic, reduce symptoms of moderate-to-severe depression better than a placebo?
What they did
This was a phase IIa trial, meaning an early test of whether a treatment works. Thirty-four adults with moderate-to-severe major depressive disorder were randomly assigned: 17 received a single 21.5 mg dose of DMT infused over 10 minutes, and 17 received placebo. Everyone also got supportive psychotherapeutic support, and neither participants nor staff knew who got what. Depression was measured after two weeks using the MADRS scale, and all participants were then offered an open-label second DMT dose.
What they found
At two weeks, the DMT group’s depression scores fell more than the placebo group’s, with a mean difference of -7.35 points on the MADRS (95% confidence interval -13.62 to -1.08; P = 0.023). In the open-label phase that followed, antidepressant effects lasted up to three months, and there was no significant difference between people who received one dose versus two. Side effects were mostly mild to moderate, most often pain at the infusion site, nausea and short-lived anxiety. No serious adverse events were reported.
The fine print
The trial was small (34 people), so the estimate of benefit is imprecise, as the wide confidence interval shows. The blinded comparison lasted only two weeks; the longer three-month results come from an open-label phase with no placebo group, so expectation effects cannot be ruled out. Psychedelics produce obvious effects, which makes true blinding difficult. This summary is based on the abstract only.
What it means
In this early, small trial, a single dose of DMT given with psychological support reduced depression symptoms more than placebo over two weeks and was generally well tolerated. Larger and longer trials are needed before firm conclusions can be drawn.
Evidence grade: Moderate. A randomized, double-blind, placebo-controlled trial, but with only 34 participants, a two-week blinded phase and an open-label extension that had no control group.
This summary is based on the study’s published abstract.