Expectancy effects—participants' beliefs about treatment—can bias the results of psychiatric randomized clinical trials by compromising blinding integrity and inflating effect sizes. This narrative review is the first to examine the interplay between expectancy, unblinding, and treatment outcomes in such trials. Evidence from experimental and clinical studies shows that expectation shapes placebo and active treatment responses. Meta-analytic data from psychedelic and anxiety disorder research indicate that unblinding due to perceived efficacy or side effects can alter effect sizes. The authors recommend collecting expectancy data and monitoring blinding integrity, and they propose developing objective outcome measures less susceptible to expectancy effects to improve trial reliability.
A living systematic review with meta-analysis examined the efficacy, safety, and all-cause discontinuation of serotonergic psychedelics and MDMA for treating mental disorders. The review found that these substances show promise in reducing symptoms of conditions such as depression, anxiety, and post-traumatic stress disorder, with some evidence supporting their therapeutic potential. However, the authors note that the overall quality of evidence is limited by small sample sizes, short follow-up periods, and methodological concerns. Safety profiles varied, with most adverse events being mild to moderate, though serious adverse events were reported in some studies. The review emphasizes the need for larger, more rigorous trials to confirm these findings.