Psychological Flexibility as a Potential Unifying Construct in Psychedelic-Assisted Psychotherapy: A Systematic Narrative Review

Abstract

As psychedelic-assisted psychotherapy (PAP) approaches clinical implementation given its robust efficacy, understanding how psychotherapy enhances serotonergic psychedelic treatment is important when designing safe therapies to treat severe mood disorders. Despite the widespread practice of psychotherapy, there is a lack of consensus on which psychotherapy is most appropriate for PAP. This systematic narrative review examined whether current evidence supports the superiority of a specific psychotherapeutic framework or instead indicates shared transdiagnostic processes. 215 records were screened via an adapted PRISMA framework, excluding studies without structured psychotherapy or non-serotonergic compounds. The resultant 24 publications address structured psychotherapeutic frameworks, mechanisms, and clinical applications. Acceptance and Commitment Therapy (ACT) emerged as the most extensively operationalized and empirically investigated framework. Cognitive Behavioral Therapy pairings show preliminary promise but remain nascent, while other frameworks, such as mindfulness-based, compassion-focused, meaning-centered, psychodynamic, and systemic approaches, exhibit limited evidence. Despite theoretical differences between frameworks, psychological flexibility repeatedly emerged as a mechanism of therapeutic change, especially within ACT-informed and mechanistic accounts of psychedelic-assisted therapy. Moreover, evidence suggests that the quantity of structured psychotherapy may influence outcomes more strongly than the specific therapeutic orientation, suggesting that psychological flexibility may not be mechanistically exclusive to ACT. These findings challenge the emphasis on identifying an optimal psychotherapy for PAP, proposing instead that future protocol development may benefit from targeting shared mechanisms such as psychological flexibility. However, direct comparative trials remain absent, highlighting a need to determine whether varying psychotherapeutic frameworks produce distinct clinical benefits or primarily operate through shared pathways of change.