The association between study design and antidepressant effects in psychedelic-assisted therapy: A meta-analysis.
Journal of affective disorders January 15, 2025 Jia-Ru Li, Kuo-Tung Chiang, Yu-Chen Kao et al. 1 citation
The antidepressant effects of psychedelics may be overestimated in trials using pre-post single-arm, non-active-drug-as-placebo, and waitlist-control designs. A systematic review of 19 trials found that psilocybin and MDMA showed large to medium effect sizes in non-active-placebo designs (psilocybin: Hedges' g = 0.87; MDMA: g = 0.65), but effects were not statistically significant in active-placebo designs. Psilocybin effect sizes were very large in pre-post (g = 2.51) and waitlist-control (g = 2.88) designs. Ayahuasca also showed large effects in pre-post (g = 1.88) and non-active-placebo (g = 1.60) designs. LSD was significant only in non-active-placebo design (g = 1.49). Limited sample sizes, difficulty maintaining participant blinding, and high expectancy likely inflate apparent efficacy.