UCLA Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, United States of America.
Pairing psilocybin with cognitive behavioral therapy (CBT) is acceptable, feasible, and associated with substantial improvements in major depressive disorder. In a small open-label trial, 16 adults with at least moderately severe depression received two psilocybin doses (10 mg and 25 mg) and 12 CBT sessions over four months. All participants completed the 7-month study with no serious adverse events. By treatment end, 13 of 16 showed at least 25% improvement in depressive symptoms, and 9 had fully remitted. Gains in depressive symptoms and psychosocial functioning were sustained three months later, with large effect sizes (Hedges' g = 1.9–2.7). Improvements correlated with better emotion regulation and more positive cognitive schemas.
Two patients in a clinical trial of psilocybin-assisted cognitive behavioral therapy for major depressive disorder had markedly different outcomes. One patient experienced powerful, beneficial effects from psilocybin that led to immediate and sustained antidepressant effects over seven months. The other patient faced significant challenges with psilocybin and reported minimal to no antidepressant effects after the drug sessions. The clinicians' experiences treating both patients are also presented. The authors theorize about future research needed to understand how psilocybin can produce the greatest psychiatric benefit, what patient conditions enable or inhibit benefit, and what psychosocial environment best facilitates psilocybin therapy.