October 28, 2022
Natalie Gukasyan, Roland R. Griffiths, David B. Yaden et al.
1 citation
preprint
Serotonergic antidepressants, such as SSRIs and SNRIs, weaken psilocybin's effects, while the non-serotonergic antidepressant bupropion has less of a dampening effect. In 595 reports of taking psilocybin with an antidepressant, the probability of weaker than expected effects was 0.48 for SSRIs, 0.56 for SNRIs, and 0.29 for bupropion. After discontinuing a serotonergic antidepressant, reduced psilocybin effects persisted for up to 3 months, with odds of reduced effects not significantly different from the first week until 3–6 months post-discontinuation. The findings suggest that serotonergic antidepressants diminish psilocybin's effects both concurrently and for months after stopping.
June 30, 2022
Sandeep M. Nayak, Bilal A. Bari, David B. Yaden et al.
1 citation
preprint
A Bayesian reanalysis of a trial comparing psilocybin (COMP360) to escitalopram for major depressive disorder found that psilocybin outperformed escitalopram, but not by a clinically meaningful amount. The analysis also found extremely strong evidence that psilocybin is non-inferior to escitalopram. Evidence for psilocybin's superiority varied by depression scale: indeterminate for one, strong for two, and extremely strong for another. For a clinically meaningful difference, evidence was moderate against it on one scale, indeterminate on two, and moderate supporting it on one. These results provide a more nuanced interpretation and support further research.
medRxiv Preprint Server
April 28, 2026
Sandeep M. Nayak, Nathan D. Sepeda, Matthew Nielsen Dick et al.
preprint
Psilocybin is being studied as a treatment for psychiatric and neurologic conditions, but there is limited comprehensive data on its cardiovascular safety. Current clinical trials typically exclude people with blood pressure of 140/90 mmHg or higher, a cutoff set conservatively without strong empirical evidence.
medRxiv Preprint Server
March 27, 2026
Brooke L. Sevchik, S. Parker Singleton, Analiese Lahey et al.
preprint
A living systematic review and meta-analysis of six randomized controlled trials with 286 participants found that MDMA-assisted therapy reduces PTSD symptoms more than control conditions (Hedges' g = -0.71). More dosing sessions and higher cumulative doses were linked to larger effects. MDMA also led to higher response (risk ratio 1.35) and remission (risk ratio 2.25) rates. Most studies had low risk of bias per Cochrane guidelines, though issues like expectancy and functional unblinding remain. The evidence was rated low certainty using GRADE, and the authors note more trials are needed.