Psilocybin (drug): Psilocybin 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: The 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.
Study summary
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.
Eligibility
Sex
ALL
Min age
21 Years
Max age
65 Years
Healthy volunteers
No
Inclusion Criteria:
* 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).
* Ability to provide written informed consent.
* Ability to read, write, speak, and understand Hebrew.
* Prior trauma-focused psychotherapy.
* Medically healthy at screening, as determined by a study physician, including:
* No exclusionary medical conditions.
* Resting blood pressure between 90/60 and 150/90 mmHg and heart rate between 45-100 bpm.
* Normal laboratory results (including liver function, renal function, and electrolytes).
Exclusion Criteria:
* 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.
* Significant suicidal risk as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS), including active suicidal ideation with intent or plan, or suicidal behavior within the past 6 months.
* Substance use disorder (excluding nicotine and caffeine); mild-to-moderate alcohol or cannabis use may be permitted under monitoring and PI approval.
* Use of psychedelic substances within 3 months before enrollment
* Participation in a clinical trial involving administration of a psychedelic substance within the past 12 months.
* History of adverse psychological reaction to psychedelics requiring hospitalization.
* Significant cardiovascular disease, including ischemic heart disease, uncontrolled hypertension, arrhythmia, or heart failure (NYHA class ≥3).
* Dementia or suspected cognitive impairment.
* Traumatic brain injury with loss of consciousness \>24 hours or post-traumatic amnesia \>7 days (unless cleared by neurological evaluation).
* Pregnancy, breastfeeding, or positive pregnancy/drug test (excluding cannabis) on the day of dosing.
* BMI \<18 or \>33
* Abnormal liver or renal function tests.
* Use of medications contraindicated with psilocybin.
* Changes in psychiatric medication (dose or type) within one month before enrollment.
* Needle phobia or inability to undergo blood testing.
Primary outcome measure(s)
Number of Participants With One or More Treatment-Emergent Adverse Events — From the first psilocybin administration session through 30 days after completion of the therapeutic intervention. 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 — From enrollment through completion of the 30-day follow-up assessment. 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.
Trial sites (1)
Facility
City
Region
Status
Tel Aviv Sourasky Medical Center
Tel Aviv
Israel
Recruiting
More Tel-Aviv Sourasky Medical Center trials in Israel
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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