Psilocybin moderately reduces depression compared to controls, with a standardized mean difference of 0.62, but effects vary widely across studies and are weaker in larger, better-controlled trials. Most of the nine randomized controlled trials (602 participants, 56% receiving psilocybin) had high risk of bias and poor harm reporting; only two studies had high-quality harm reporting. Therapeutic mechanisms of action were discussed but rarely tested, leaving it unclear how psilocybin alleviates depression. Smaller studies showed stronger effects favoring psilocybin, and nearly all studies reported financial conflicts of interest. Independent, larger trials with active controls and mechanism assessments are needed.
MDMA-assisted therapy (MDMA-AT) shows a moderate-to-large reduction in psychological symptoms compared to control conditions, based on a meta-analysis of eight controlled trials with 295 participants. The effect was larger against inert placebos than active controls. Trauma symptoms improved strongly, while depression showed a smaller, non-significant effect. Only 23% of publications met high-quality standards for reporting harms. Small samples and mediocre harm reporting underscore the need for larger, more transparent trials.