Transdiagnostic Outcomes from Yale's Real-World Psilocybin Trial: Connecticut-Funded Pioneering Psychedelic Therapy Program and Insights from Other State Initiatives

Psilocybin-assisted therapy has shown promise across mental health conditions, yet clinical trials typically focus on narrow, diagnostically defined populations. This presentation explores preliminary findings from a transdiagnostic open-label study investigating how psilocybin treatment impacts cognitive flexibility and psychological functioning in individuals with diverse psychiatric symptoms. The inclusion of mixed-diagnosis participants maintaining standard psychiatric medications (including SSRIs) enhances real-world clinical applicability.The study employs a single psilocybin administration (25mg) with psychotherapeutic support, targeting transdiagnostic processes such as rumination and emotional regulation. Data collection includes daily diary methods, behavioral assessments of cognitive flexibility through advanced computational modeling and probabilistic reversal learning tasks, and self-report measures including the WHODAS 2.0 (measure of functioning).Preliminary data from five enrolled participants show improvements in both cognitive flexibility and clinical outcomes. This study is significant for its real-world generalizability, broad inclusion criteria, and focus on mechanisms of change across diverse psychiatric conditions. By adopting an open-label design, we provide valuable insights into the practical application and scalability of psilocybin therapy. Attendees will gain an understanding of the challenges and opportunities of conducting transdiagnostic psychedelic research, as well as implications for clinical practice and future studies.