Recent phase 2 studies indicate that psilocybin-assisted therapy has potential benefits for various neuropsychiatric conditions, including major depressive disorder (MDD). This study explored whether improvements in psychological flexibility mediate these therapeutic effects. In a placebo-controlled study, participants with moderate-to-severe MDD received a placebo followed by psilocybin four weeks later, integrated within acceptance and commitment therapy (ACT). The study measured depression severity, psychological flexibility, mindfulness, and values-congruent living over 16 weeks.

Results showed significant and sustained improvements in psychological flexibility, mindfulness, and values-congruent living post-psilocybin, with these improvements strongly associated with reductions in depression severity. The findings suggest that integrating psilocybin treatment with ACT can enhance psychological flexibility, contributing to the reduction of depressive symptoms. This study supports the idea that psychological flexibility is a key mechanism in the therapeutic effects of psilocybin-assisted therapy for MDD.

Reference: Sloshower J, Zeifman RJ, Guss J, et al. Psychological flexibility as a mechanism of change in psilocybin-assisted therapy for major depression: results from an exploratory placebo-controlled trial. Sci Rep. 2024;14(1):8833. doi: 10.1038/s41598-024-58318-x.