Psilocybin-assisted cognitive behavioral therapy for major depressive disorder: A pilot trial.

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.

Study at a glance

Abstract

Psilocybin-assisted therapy has emerged as a promising treatment for major depressive disorder, but little attention has been paid to the psychotherapy that adjoins psilocybin. Providing an adjunctive psychotherapy that is manualized and evidence-based may make psilocybin treatment more acceptable, effective, and disseminable. We examined the acceptability, feasibility, and clinical outcomes of psilocybin paired with cognitive behavioral therapy (CBT) for major depressive disorder. Participants were adults with major depressive disorder who presented with at least moderately severe depressive symptoms. All participants underwent psilocybin-assisted CBT (PA-CBT), which consisted of two psilocybin doses (10 mg and 25 mg separated by one month) interspersed with 12 psychotherapy sessions over four months. Participants' depressive symptoms, psychosocial functioning, and cognitive-affective responses were collected at the study's baseline, at the completion of PA-CBT, and three months post-treatment. Sixteen participants were enrolled, and all were retained through the 7-month study. PA-CBT was rated as highly acceptable by participants and study clinicians, with no serious adverse events reported. Based on independent assessments, 13 of 16 participants showed at least moderate (≥ 25%) improvement in depressive symptoms by the end of treatment, and 9 had fully remitted. Pre-to-post treatment improvements in depressive symptoms and psychosocial functioning were sustained at the 3-month follow-up (Hedges' gs = 1.9-2.7). Changes in depressive severity during the treatment were associated with improvements in emotion regulation and positive and negative cognitive schemas. CBT appears to be a feasible, well-accepted, and beneficial adjunct to psilocybin treatment. Future randomized trials are needed to compare the efficacy of PA-CBT with other psilocybin-assisted therapy modalities.