Reconstructing the Self: How Psychedelic-Assisted Therapy Reshapes Mental Health Through Shifts in Self-Attitudes

Psilocybin produces a wide range of effects including alterations in perception, affect, cognition, and sense of self. However, the impact of PAT on psychological attitudes toward the self—and its significance in driving therapeutic outcomes—remains underexplored. Therefore, using novel data from multiple studies, this presentation will explore the effects of psilocybin-assisted therapy (PAT) on attitudes toward the self and its role as a mechanism underlying PAT’s therapeutic effects. Dr. Zeifman will present original data from an observational study and a randomized controlled trial for major depressive disorder showing that psilocybin produces acute experiences of self-compassion that predict improvements in mental health. He will also present original data from three quasi-controlled studies (healthy individuals [Zeifman et al., in press], anorexia nervosa, and fibromyalgia) indicating that PAT decreases negative attitudes toward the self, alongside the neurobiological mechanisms and clinical outcomes associated with these findings. Dr. Agin-Liebes will present both quantitative and qualitative findings from clinicals trials of PAT for alcohol use disorder (AUD), obsessive compulsive disorder (OCD), and functional impairment in a transdiagnostic population. These studies reveal that PAT significantly enhances self-compassion and diminishes self-criticism, with large effects. Qualitative analyses further illuminate experiences of self-compassion and their integral role in facilitating change (Agin-Liebes et al., 2024). Together, this presentation underscores the transdiagnostic relevance of self-attitudes in psychedelic therapy and explores their implications for refining and optimizing PAT, offering new avenues for enhancing mental health treatment.