Psilocybin-assisted cognitive behavioral therapy for major depressive disorder: A pilot trial
A small, open-label pilot study testing a structured combination of cognitive behavioral therapy (CBT) and psilocybin for adults with major depressive disorder (MDD).
This was a small, open-label pilot study testing a structured combination of cognitive behavioral therapy (CBT) and psilocybin for adults with major depressive disorder (MDD). Sixteen participants received 12 CBT sessions plus two psilocybin sessions (10 mg and 25 mg) over four months and were followed for an additional three months.
The study provides early evidence that psilocybin-assisted CBT is feasible, safe, highly acceptable, and associated with large reductions in depressive symptoms, with more than half of participants reaching remission and benefits lasting at least three months. However, because it was a small uncontrolled pilot trial, the results should be viewed as promising rather than definitive until confirmed in randomized controlled studies
Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.
Weintraub MJ, Jeffrey JK, Ichinose MC, Bergman RL, Shapiro B, Barnett G, Artin H, Lynn M, Salimian A, Grody S, Ramesh R, Eales L, Grob CS, Miklowitz DJ. Psilocybin-assisted cognitive behavioral therapy for major depressive disorder: A pilot trial. J Affect Disord. 2026 Jun 15;403:121423. doi: 10.1016/j.jad.2026.121423. Epub 2026 Feb 16. PMID: 41707717; PMCID: PMC13138500. Read Paper
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