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

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.