Am J Psychiatry

Single-dose psilocybin shows promise for severe treatment-resistant depression

January 10, 2025

Study details: This open-label trial evaluated the safety and efficacy of a single 25-mg dose of synthetic psilocybin in 12 adults (mean age, 40.6 years) with severe treatment-resistant depression, defined as non-response to ≥5 prior treatments. Conducted over 12 weeks, the study included pre-treatment, dosing day, and post-treatment integration sessions. The primary outcome was the change in Montgomery-Åsberg Depression Rating Scale (MADRS) scores at 3 weeks post treatment, with secondary measures extending to 12 weeks.

Results: Significant reductions in depressive symptoms were observed at both 3 weeks (MADRS mean change, -15.8) and 12 weeks (MADRS mean change, -17.2) post-treatment. The Oceanic Boundlessness dimension of the psychedelic experience correlated with antidepressant responses. However, patients with comorbid PTSD showed a reduced antidepressant effect.

Clinical impact: Psilocybin may be a viable option for patients with severe treatment-resistant depression, particularly those without comorbid PTSD.

Source:

Aaronson ST, et al. (2025, January 1). Am J Psychiatry. Single-Dose Psilocybin for Depression With Severe Treatment Resistance: An Open-Label Trial. https://pubmed.ncbi.nlm.nih.gov/39741440/