CONNECTEDNESS AS A MECHANISM OF CHANGE IN PSILOCYBIN-ASSISTED COGNITIVE BEHAVIORAL THERAPY

Background

Psilocybin-assisted therapy has shown robust antidepressant effects among individuals with major depressive disorder (MDD); however, mechanisms of the treatment remain unclear. While depression has been conceptualized as a disorder of disconnection, psilocybin is thought to facilitate connectedness. This analysis of an openlabel trial of psilocybin-assisted cognitive behavioral therapy (PA-CBT) examined changes in connectedness over the treatment and its associations with depressive symptoms and psychosocial functioning.

Methods

Adults with MDD were enrolled in PA-CBT, which included twelve psychotherapy sessions and two psilocybin sessions (10 mg, 25 mg) over 4 months and were followed for 3 months post-treatment. Connectedness was measured using the Watts Connectedness Scale, depressive symptoms with the Hamilton Depression Rating Scale, and psychosocial functioning with the Global Assessment of Functioning. Linear mixed-effects regression models examined changes over time in connectedness and its associations with depressive symptoms and psychosocial functioning. Connectedness was also examined as a mediator in the relationship between psychedelic effects (mystical experiences and psychological insights) and depressive symptoms.

Results

Among fifteen participants, connectedness increased significantly from baseline to post-treatment (Hedges’ g = 0.62), though these changes were not sustained at follow-up. Higher connectedness over the treatment period was associated with improved depressive symptoms and psychosocial functioning across the seven-month study (p < 0.001). Increased connectedness from baseline to post-treatment predicted improved depressive and functioning outcomes at follow-up, controlling for baseline scores. There was preliminary evidence of connectedness as a mediator between psychedelic effects and depressive symptom improvement.

Conclusion

This study provides further quantitative evidence that connectedness may be a mechanism by which psilocybin treatment benefits individuals with MDD. Future larger randomized controlled trials, including our ongoing trial comparing PA-CBT to standard psilocybin-assisted therapy, are needed to clarify whether connectedness functions as a treatment-specific mechanism and to develop interventions that sustain connectedness over time.