This is an open-label pilot study designed to evaluate the safety, tolerability, and preliminary clinical effects of psilocybin-enhanced trauma-focused psychotherapy in individuals with post-traumatic stress disorder (PTSD).
Participants will receive a structured therapeutic protocol that includes preparatory sessions, two psilocybin administration sessions (15 mg followed by 25 mg), and integration sessions based on a trauma-focused therapeutic approach.
The primary objective of the study is to assess the safety and tolerability of psilocybin administration in this clinical population. Secondary objectives include evaluating changes in PTSD symptom severity, as measured by the Clinician-Administered PTSD Scale (CAPS-5), at 30 days following treatment.
This pilot study will include 13 participants and is intended to inform the feasibility and design of a subsequent randomized controlled trial.
Age 21-65 years.
Diagnosis of post-traumatic stress disorder (PTSD) according to DSM-5 criteria, as assessed by CAPS-5.
At least 1 year since the traumatic event.
Moderate or greater PTSD severity (CAPS-5 score ≥ 25).
Current or past diagnosis of psychotic disorders, bipolar disorder, schizoaffective disorder, dissociative identity disorder, or borderline personality disorder (as assessed by MINI or SCID-5-SPQ).
Current psychotic features.
First-degree relative with a history of a psychotic disorder.
History of antidepressant-induced mania or hypomania.
Single group
Psilocybin (drug)
DrugPsilocybin is a naturally occurring psychedelic compound and a prodrug of psilocin, which exerts its effects primarily through serotonergic receptor activity. In this study, psilocybin is administered orally in two dosing sessions (15 mg followed by 25 mg) in a controlled clinical setting, with a minimum interval of one week between sessions. Administration is performed by a study physician, who provides medical oversight, monitors vital signs, and evaluates acute responses. Participants are prepared through preparatory psychotherapy sessions and remain in the clinic during the acute drug effects. Each session lasts approximately six hours, after which participants are discharged following physician evaluation. Integration psychotherapy sessions follow each dosing session. After each dosing session, participants are accompanied home by a designated escort or transported by taxi to their care. The first integration psychotherapy session is held the following morning.
Trauma-Focused Psychotherapy
BehavioralThe psychotherapy intervention is based on an integrative trauma-focused framework combining Acceptance and Commitment Therapy (ACT) and Narrative Exposure Therapy (NET). Psilocybin-assisted psychotherapy aims to facilitate emotional processing, psychological flexibility, and contextual integration of traumatic memories within a coherent autobiographical narrative. The intervention is delivered by a licensed therapist and includes two preparatory sessions, two psilocybin dosing sessions, and three integration sessions following each dosing session (six in total). Preparation focuses on therapeutic alliance and readiness for the psychedelic experience. Integration sessions support trauma processing, meaning-making, and incorporation of insights into daily functioning. The approach emphasizes flexible re-engagement with trauma-related memories while fostering a broader and more adaptive sense of self.
Number of Participants With One or More Treatment-Emergent Adverse Events
Treatment-emergent adverse events (TEAEs) are defined as any medical or psychological adverse event that begins or worsens after the first psilocybin administration. The reported outcome will be the number of participants experiencing at least one TEAE from the first dosing session through the 30-day follow-up period. Treatment-emergent adverse events (TEAEs) will be identified through clinical assessments conducted by the study physician and psychologist, monitoring of vital signs (blood pressure and heart rate), participant self-reports, administration of the Columbia-Suicide Severity Rating Scale (C-SSRS) to assess suicidal ideation and behavior, and the Swiss Psychedelic Side Effects Inventory (SPSI) to systematically assess psychedelic-related side effects. Serious adverse events (SAEs) will be monitored, documented, and reported in accordance with the study safety reporting procedures.
Number of Participants Completing the Full Therapeutic Intervention
Feasibility and tolerability will be assessed by the number of participants who successfully complete the full therapeutic intervention, defined as completion of both psilocybin administration sessions and all protocol-required preparatory and integration psychotherapy sessions. Successful completion of the intervention reflects the feasibility of implementing the study protocol as planned and the tolerability of the intervention.
Change in PTSD Symptom Severity as Measured by CAPS-5
PTSD symptom severity will be assessed using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5). The outcome measure will reflect the change in CAPS-5 total score from baseline to 30 days after completion of the therapeutic intervention.
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Tel-Aviv Sourasky Medical Center
Lead sponsor
Tel Aviv University Sagol School of Neuroscience
Collaborator
