Trauma-informed Psilocybin Assisted Psychotherapy (TiPAP) for PTSD

This study is an open-label pilot clinical trial evaluating the safety, tolerability, and preliminary clinical effects of psilocybin-enhanced trauma-focused psychotherapy for the treatment of post-traumatic stress disorder (PTSD). PTSD is a chronic and disabling condition characterized by intrusive symptoms, avoidance, negative alterations in cognition and mood, and hyperarousal. Despite the availability of evidence-based psychotherapies and pharmacological treatments, a substantial proportion of patients do not achieve sufficient symptom relief, highlighting the need for novel and rapid-acting interventions. Psilocybin, a serotonergic psychedelic compound, has demonstrated potential therapeutic effects in a range of psychiatric conditions, including depression, anxiety, and trauma-related disorders. When administered in a controlled therapeutic setting, psilocybin may facilitate emotional processing, cognitive flexibility, and adaptive reorganization of trauma-related memories. In this study, psilocybin administration is combined with an integrative trauma-focused psychotherapeutic framework based on principles of Acceptance and Commitment Therapy (ACT) and Narrative Exposure Therapy (NET). ACT emphasizes psychological flexibility, acceptance, self-as-context, and values-based action, supporting individuals in changing their relationship with trauma-related internal experiences. NET complements this approach by facilitating the structured integration of traumatic memories within a coherent autobiographical narrative, embedding the traumatic experience within the broader context of the individual's life story. Together, this framework is designed to support the processing of traumatic experiences within an expanded and flexible cognitive-emotional context, promoting adaptive meaning-making and reconnection with a broader sense of self. Participants will undergo a structured treatment protocol consisting of preparatory sessions, two psilocybin administration sessions (15 mg for the first session and 25 mg for the second session), and post-session integration sessions. The study physician retains clinical authority to discontinue a dosing session or withdraw a participant at any time, including in the event of sustained cardiovascular distress, severe psychological distress unresponsive to support, or acute psychiatric decompensation. The primary objective of the study is to evaluate the safety and tolerability of psilocybin administration in individuals with PTSD. Safety will be assessed through monitoring of adverse events and clinical observations throughout the study. Secondary objectives include assessing changes in PTSD symptom severity using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) at 30 days following the intervention. This pilot study will enroll 13 participants and is intended to provide preliminary data on feasibility, safety, and potential clinical effects to inform the design of a future randomized controlled trial.