Single DMT Dose Shows Promise in Cutting TRD Symptoms

NEW YORK – A single intravenous dose of the psychedelic compound dimethyltryptamine (DMT), combined with psychological support, produced rapid and sustained reductions in depressive symptoms among adults with moderate-to-severe major depressive disorder, according to results from a small Phase 2a clinical trial.

The study, published in Nature Medicine, involved 34 participants with treatment-resistant depression (TRD). Researchers from Imperial College London and collaborators conducted a double-blind, placebo-controlled trial in which participants received either a 21.5 mg dose of DMT fumarate (SPL026 by Helus Pharma Inc.) or placebo infused over 10 minutes. All received preparatory and integrative psychotherapy sessions.

The primary endpoint was the change in Montgomery–Åsberg Depression Rating Scale (MADRS) scores at two weeks. The DMT group showed a statistically significant greater reduction compared to placebo (mean difference of -7.35 points; 95% CI, -13.62 to -1.08; P=0.023). At two weeks, 35% of the DMT group met response criteria (at least 50% reduction in MADRS score), compared with 12% in the placebo group. Remission rates (MADRS score of 10 or lower) were 29% versus 12%.

In an open-label extension phase, all participants received a second DMT dose. Antidepressant effects persisted for up to three months, with no clear additional benefit observed from the second dose compared with the single-dose group. Some reports from follow-up assessments suggested benefits lasting as long as six months in certain individuals.

The treatment appeared generally well-tolerated. Most adverse events were mild to moderate and included pain at the infusion site, nausea and short-lived anxiety. No serious adverse events were recorded.

DMT, a short-acting serotonergic psychedelic found in ayahuasca and other traditional preparations, produces effects lasting roughly 20 to 30 minutes [shorter than those of psilocybin or LSD] potentially making it more practical for clinical settings while still delivering meaningful therapeutic outcomes.

The trial’s small size and early-phase status mean the results should be viewed cautiously. Larger studies will be required to verify the findings, explore optimal dosing regimens and determine how the approach performs across more diverse patient groups.

For the psychedelics sector, the data contribute to a growing body of evidence on rapid-acting interventions for depression. Helus Pharma Inc. (rebranded from Cybin Inc., the original developer of SPL026) continue to advance such compounds through development pipelines. While these early signals are encouraging, the path to regulatory approval and widespread clinical use remains long and subject to further rigorous testing.