Single-Dose Psilocybin Linked With Rapid, Sustained Gains in Patients With MDD

A single 25-mg dose of psilocybin plus psychological support was associated with a statistically and clinically significant improvement in depressive symptoms compared with active placebo in adults with major depressive disorder (MDD), according to a study published in JAMA.

“Improvements in depression were apparent within 8 days of psilocybin dosing, consistent with a rapid onset of action, and were maintained across the 6-week follow-up period, without attenuation of the effect, and with higher point prevalence rates of Montgomery-Asberg Depression Rating Scale (MADRS)-defined response and remission than has been observed in recent psilocybin studies of treatment-resistant depression,” wrote corresponding author Charles L. Raison, MD, Psych Congress Network Depression Section Editor, Usona Institute in Fitchburg, Wisconsin, and study coauthors. “These findings add to evidence that psilocybin—when administered with psychological support—may hold promise as a novel intervention for MDD."

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The phase 2 trial included 104 patients with MDD at 11 research sites in the United States. Among them, 51 patients were randomized to a 25-mg dose of synthetic psilocybin and 53 patients were randomized to a 100-mg dose of niacin. The capsules for psilocybin and niacin appeared identical, and each was administered with psychological support.

Scores on the MADRS, on which higher scores signal more severe depression, were significantly reduced with psilocybin compared with placebo between baseline and day 43 as well as between baseline and day 8. The mean difference between treatments was −12.3 on day 43 and −12.0 on day 8 in favor of psilocybin, according to the study.

Between baseline and day 43, the psilocybin group also had significantly reduced Sheehan Disability Scale scores compared with niacin; researchers reported a mean difference of −2.31. 

More participants had sustained depressive symptom response with psilocybin than with niacin. Sustained depressive symptom remission did not differ significantly between interventions, the study found.

Psilocybin was associated with a higher rate of overall and severe adverse events, although there were no serious treatment-emergent adverse events.

Reference

Raison CL, Sanacora G, Woolley J, et al. Single-dose psilocybin treatment for major depressive disorder: a randomized clinical trial. JAMA. 2023;330(9):843-853. doi: 10.1001/jama.2023.14530