Clinical Pharmacology & Therapeutics
October 5, 2023
Robert H. Dworkin, Michael Mcdermott, Sandeep M. Nayak et al.
16 citations
Combining a classic psychedelic (e.g., psilocybin) with psychotherapy may produce benefits that are synergistic—greater than the sum of each treatment alone—but current trials have not tested this directly. Most studies pair the drug with some form of psychological support, yet providing full psychotherapy is more costly and harder to scale than basic harm-reduction support. Factorial designs, in which patients are randomly assigned to drug plus psychotherapy, drug alone, psychotherapy alone, or double placebo, can isolate the separate contributions of each component and detect true synergy. Such trials require large sample sizes but could determine whether the added expense of psychotherapy is worthwhile for improving outcomes in conditions like depression, anxiety, and chronic pain.
Nature Mental Health
May 1, 2026
S. Parker Singleton, Brooke L. Sevchik, Analiese Lahey et al.
2 citations
A living systematic review and meta-analysis of 15 randomized controlled trials (801 participants) found that psilocybin-assisted therapy substantially reduces depressive symptoms compared to control conditions, with a standardized mean difference of −0.90 (Hedges’ g). The analysis included 12 trials (585 participants) in the primary model. Many studies had small sample sizes or risk of bias. The review is maintained as a living resource with an open-data database and online dashboard that will be updated as new evidence emerges.
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.
medRxiv
August 16, 2025
S. Parker Singleton, Brooke L. Sevchik, Analiese Lahey et al.
preprint
Psilocybin-assisted therapy produces substantial reductions in depressive symptoms compared to control conditions, according to a systematic review and meta-analysis of 12 randomized controlled trials with 711 participants. The pooled effect size was large (Hedges' g = –0.91), and effects appeared rapidly and remained consistent over several weeks. However, many studies had small sample sizes or risk of bias, and waitlist-controlled or crossover designs contributed heterogeneity. The review provides a living open data resource that will be updated as new evidence emerges.