JAMA Psychiatry

Psychedelic therapy and antidepressants show similar effects when blinding is equalized

March 19, 2026

In a systematic review and meta-analysis, investigators compared psychedelic-assisted therapy with standard antidepressants for depression under conditions designed to equalize unblinding across treatment arms. When differences in expectancy and treatment awareness were accounted for, psychedelic therapy did not demonstrate clear superiority over conventional antidepressants in reducing depressive symptoms. The findings suggest that previously reported advantages of psychedelics may be partly driven by functional unblinding and expectancy effects rather than pharmacologic efficacy alone. The authors emphasize the methodological difficulty of maintaining blinding in psychedelic trials and call for more rigorous designs to clarify true comparative effectiveness.

Clinical takeaway: Until higher-quality, better-blinded trials are available, clinicians should interpret claims of superior antidepressant efficacy with caution and continue to base treatment decisions on established therapies, patient preferences, safety profiles, and access to care.

Source:

Williams ZJ, et al. (2026, March 18). JAMA Psychiatry. Psychedelic Therapy vs Antidepressants for the Treatment of Depression Under Equal Unblinding Conditions: A Systematic Review and Meta-Analysis. https://pubmed.ncbi.nlm.nih.gov/41848744/