A comprehensive systematic review and meta-analysis of 13 studies found that MDMA-assisted psychotherapy (MDMA-AP) is associated with increased odds of side effects compared to control conditions. In Phase 2 trials, MDMA-AP roughly doubled the odds of any side effect during medication sessions and in the following week. In Phase 3 trials, the odds of any adverse event during treatment were about 3.5 times higher with MDMA-AP than with placebo-assisted psychotherapy. Most side effects were transient and mild or moderate. However, the evidence had very low to moderate certainty, most trials had high risk of bias, and none adequately followed CONSORT Harms 2022 reporting guidelines, highlighting the need for further safety research.
Side-effects reporting in clinical trials of psilocybin-assisted psychotherapy (PAP) for psychiatric conditions is inconsistent but improving over time. A systematic review of 24 trials published between 2005 and 2024 found that only six had high-quality side-effects reporting, while nine were low and five were very low. All nine randomized controlled trials showed high risk of bias for side-effects outcomes. There was no evidence of systematic underreporting in published articles compared with trial registers, but variability in reporting hindered comparisons. The authors conclude that existing evidence has a high risk of bias and that future trials should follow best-practice guidelines, and discussions with patients should emphasize current uncertainty about PAP side-effects.