7 - (IOP 38) Psilocybin-assisted Cognitive Behavioral Therapy for Major Depressive Disorder - Results from Open Trial

Background. Psilocybin-assisted therapy has emerged as a therapeutic agent for a range of mental disorders, including major depressive disorder. While the drug has received the bulk of attention, the psychotherapy component has been virtually unexamined. As such, there is a significant need for a protocolized psychosocial treatment that can be tested and optimized to adjoin psilocybin treatment for major depression. Cognitive behavioral therapy’s (CBT’s) action-oriented approach, providing tangible skills in sessions and encouraging between-session practice may enhance the effects of psilocybin. Psilocybin may also help improve the efficacy of CBT through its facilitation of cognitive flexibility and openness to new experiences.
Methods. We have protocolized a psilocybin-assisted cognitive behavioral therapy (PA-CBT) for adults with major depressive disorder. PA-CBT includes the core safety elements of standard psychedelic-assisted therapy, two psilocybin sessions (10mg & 25mg), and 12 sessions of cognitive behavioral therapy. Participants were enrolled in an open trial of the 4-month PA-CBT treatment. The study's goals are to examine the treatment’s feasibility, acceptability, and clinical effects from pre-treatment to 3 months post-treatment (7-month trial, overall). Primary outcomes pertaining to feasibility include recruitment and retention data. We are also collecting quantitative measures of participant and therapist acceptability and clinical outcomes (i.e., depressive symptom severity and psychosocial functioning).
Results. We will present data on the 16 participants who have enrolled in our open trial of PA-CBT. Of the 16 enrolled participants, 9 have completed the 7-month trial, 5 have completed the treatment and are awaiting their 3-month follow-up assessment, and 2 are currently mid-way through the study treatment. All enrolled participants have been retained through the study. Preliminary data suggest high acceptability and feasibility of the treatment. Based on self-report and study-assessor ratings, participants have also shown significant improvements in depressive symptoms and psychosocial functioning from pre-treatment through the 3-month follow-up period. Finally, we will preview the follow up to this study - an NIH-funded randomized controlled trial comparing PA-CBT to psilocybin treatment with minimal therapeutic support for major depression.
Conclusion. Data suggest that cognitive behavioral therapy pairs well with psilocybin treatment for major depressive disorder. This research answers critical questions about the acceptability and feasibility of combining standard psilocybin treatment with one of the gold-standard psychotherapies (CBT) for major depressive disorder. The study also indicates the initial effects by which CBT can influence participants’ depressive severity and psychosocial functioning. This work will lead to the development of a manualized, evidence-based psilocybin-assisted therapy that can be further studied, optimized, and potentially disseminated to clinicians.