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Clinical conceptualisation of PTSD in psilocybin treatment: disrupting a pre-determined and over-determined maladaptive interpretive framework

Nadav Liam Modlin, Victoria Williamson, Carolina Maggio, Joanne Stubley, James Rucker, Namik Kirlic, Anthony J. Cleare

Therapeutic Advances in Psychopharmacology June 8, 2025 DOI: 10.1177/20451253251342319 via OpenAlex

Summary

AI-generated from the abstract

PTSD is a common and debilitating condition that current treatments only partially address. This review examines psilocybin, a classical psychedelic, as a potential therapeutic agent. It synthesizes recent literature on psychedelic therapies for trauma-related conditions, including treatment-resistant depression and end-of-life anxiety. The authors propose a conceptual framework viewing PTSD as a maladaptive interpretive framework that psilocybin may disrupt through its psychopharmacological properties and subjective effects. A clinical narrative illustrates this process. Recommendations emphasize rigorous, trauma-informed protocols for safe administration in medical research settings.

Study at a glance

Characteristics Review Peer reviewed
Intervention Psilocybin
Topics Anxiety Psilocybin
Keywords Psychotherapist Cognition Clinical psychology
Citations 1
Key finding Psilocybin may disrupt the rigid, maladaptive interpretive framework underlying PTSD, facilitating therapeutic progress.

Abstract

Post-traumatic stress disorder (PTSD) and associated trauma and stressor-related disorders are common and debilitating, presenting significant treatment challenges due to their complex interplay of biological, cognitive, affective, somatic and social factors. Current treatments, while advancing and effective, yield limited efficacy for many individuals, underscoring the need for novel therapeutic approaches. This review explores the multifaceted nature of PTSD, emphasising its intricate predisposing and maintaining factors and explores the potential of psilocybin, a classical psychedelic, as a therapeutic agent. This review synthesises recent literature on the safety, efficacy and proposed mechanisms of action and change of psychedelic therapies for psychiatric conditions associated with traumatic stress, including treatment-resistant depression, end-of-life anxiety and anorexia nervosa. Correspondingly, it proposes a conceptual framework for psilocybin treatment in PTSD, framing the condition as a complex, maladaptive interpretive framework that is both predetermined and over-determined. A clinical narrative illustrates how psilocybin’s unique psychopharmacological properties and catalysed subjective effects may facilitate therapeutic progress by disrupting this rigid and restricting framework. Finally, we offer recommendations for the safe administration of psilocybin for traumatised patients in medical research settings, emphasising the importance of rigorous and trauma-informed protocols and comprehensive patient care.

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