Psychedelic therapy and traditional antidepressants show similar depression improvement in open-label comparisons, challenging prior trial advantages

Psychedelic therapy and standard antidepressants show similar improvements for depression when outcomes are compared under open-label conditions. A meta-analysis in JAMA Psychiatry addresses a key psychedelic-trial problem called functional unblinding, where participants often realize whether they received psychedelic or placebo because effects are too obvious to hide. Without effective blinding, expectation and disappointment can shift results through placebo group frustration and increased hope in the active group. The study compares treatment effects on a level playing field by looking at open-label antidepressant trials alongside psychedelic therapy trials. Across 24 trials (16 open-label antidepressant trials with 7,921 participants and 8 psychedelic therapy trials with 249 participants), both approaches reduced Hamilton Depression Rating Scale scores, with no meaningful difference between them. The findings also suggest outcome inflation in earlier blinded psychedelic studies may reflect know-cebo effects rather than a uniquely larger drug effect. The authors note limitations like differences in patient populations and follow-up timelines, and emphasize that core symptom reduction was the focus rather than functional outcomes or side-effect differences.