Phase 2a Trial Meets Endpoints for Psychedelic SPL026 to Treat Major Depressive Disorder

Helus Pharma’s SPL026 met its primary endpoint in a phase 2a trial, showing clinically significant reduction in depression symptoms.^1,2 The drug, a form of intravenous dimethyltryptamine (DMT) psychedelic, showed antidepressant effects within a week of treatment, and sustained effects for up to 3 months.

“We have shown that a single dose of SPL026 is safe, effective and durable, with treatment effects comparable to other promising interventional treatments often requiring much longer treatment sessions,” said David Erritzoe, MD, PhD, lead investigator of the trial. He added that “although such early trial results should always be interpreted with some caution, these data show the promise of DMT as a potentially more cost-effective treatment for clinical depression than related serotonergic agonists with longer psychoactive action due to the shorter dosing sessions.”

The phase 2a study enrolled 34 participants with moderate to severe major depressive disorder who received either a single dose of DMT or placebo. Study participants were 29.4% female, predominantly white, had experienced depression for an average 10.5 years, and had a mean age of 32.8 years. Patients in the treatment group received a single 21.5 mg dose of intravenous DMT fumarate (SPL026) over 10 minutes, along with psychotherapeutic support. The primary endpoint measured was change in Montgomery-Asberg Depression Rating Score (MADRS) at 2 weeks. Secondary endpoints included response and remission, as measured by 50% or greater reduction in MADRS score and MADRS score of 10 or less, respectively. An open label portion of the study offered participants a second dose of the medication 2 weeks after the first administration.

At 2 weeks after drug administration, the treatment group showed a significant reduction in MADRS score compared with placebo (P = 0.023). In the open label addition, antidepressant effects were sustained up to 3 months, though there were no significant differences between patients who received 1 vs 2 doses. In some patients, antidepressant effects lasted up to 6 months. Treatment effects were observable at 1 week (P = 0.002), and response rates at 2 weeks were 35% for those treated, compared with 12% for placebo. Remission rates were also higher at week 2, with 29% in the treatment group and 12% in the placebo group. Adverse effects were mostly mild to moderate, the study stated, consisting mainly of infusion site pain, nausea, and transient anxiety. The drug was generally well-tolerated, and the study saw no serious adverse events reported.

Study authors noted that there was a greater sustained response in the placebo group, potentially related to a longer preparatory phase before dosing. “Extended therapist–participant interaction may have facilitated a stronger therapeutic alliance, which is increasingly recognized as a key contributor to outcomes in psychedelic-assisted therapy. While this remains speculative, the trend observed here highlights the need for future studies that both minimize attrition and directly measure therapeutic alliance to better understand its role in shaping long-term treatment effects,” investigators explained.

Helus Pharma, developer of SPL026, does not plan to advance the drug in its current form, but stated that the mechanistic and clinical insights from the trial will continue to inform the company’s drug development programs.

References

1. Nature Medicine publishes Helus Pharma’s randomized, placebo-controlled phase 2a trial of SPL026 in major depressive disorder. Press release. February 17, 2026. Accessed February 17, 2026. https://www.globenewswire.com/news-release/2026/02/17/3239141/0/en/Nature-Medicine-Publishes-Helus-Pharma-s-Randomized-Placebo-Controlled-Phase-2a-Trial-of-SPL026-in-Major-Depressive-Disorder.html

2. Erritzoe D, Barba T, Benway T, et al. A short-acting psychedelic intervention for major depressive disorder: a phase 2a randomized placebo-controlled trial. Nature Med. 2026.