Trauma-informed Psilocybin Assisted Psychotherapy (TiPAP) for PTSD

NCT07737054 | Recruiting Early Phase 1

• 2 other identifiers: 0101-24-PILOTInternal Study ID
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Post-Traumatic Stress Disorder, PTSD

Keywords

Psilocybin; Psychedelic-Assisted Therapy; Trauma-Focused Therapy; Acceptance and Commitment Therapy; PTSD; ACT; Rapid-Acting Treatment; Psychotherapy; Pilot Study

Outcome Measures

Primary Outcomes (2)

• 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.

  From the first psilocybin administration session through 30 days after completion of the therapeutic intervention.

• 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.

  From enrollment through completion of the 30-day follow-up assessment.

Secondary Outcomes (1)

• Change in PTSD Symptom Severity as Measured by CAPS-5

  Baseline to 30 days after completion of the therapeutic intervention

Study Arms (1)

Psilocybin-Assisted Trauma-Focused Psychotherapy

EXPERIMENTAL

Participants receive a structured clinical intervention combining preparatory psychotherapy sessions, two psilocybin dosing sessions (15 mg and 25 mg), and integration psychotherapy sessions within a trauma-focused therapeutic framework.

Drug: Psilocybin (drug); Behavioral: Trauma-Focused Psychotherapy

Interventions

Psilocybin (drug) 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.

Psilocybin-Assisted Trauma-Focused Psychotherapy

Trauma-Focused Psychotherapy BEHAVIORAL

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.

Psilocybin-Assisted Trauma-Focused Psychotherapy

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Tel-Aviv Sourasky Medical Center: lead
• Tel Aviv University Sagol School of Neuroscience: collaborator

Study Sites (1)

Tel Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

RECRUITING

Related Publications (6)

• Neisewander B, Moreau C. Trauma-Focused ACT: A Practitioner's Guide to Working With Mind, Body, and Emotion Using Acceptance and Commitment Therapy. Am J Psychother. 2024 Dec 12;77(4):215-216. doi: 10.1176/appi.psychotherapy.20240018. Epub 2024 Nov 6. No abstract available.

  PMID: 39504448 BACKGROUND

• Mitchell JM, Ot'alora G M, van der Kolk B, Shannon S, Bogenschutz M, Gelfand Y, Paleos C, Nicholas CR, Quevedo S, Balliett B, Hamilton S, Mithoefer M, Kleiman S, Parker-Guilbert K, Tzarfaty K, Harrison C, de Boer A, Doblin R, Yazar-Klosinski B; MAPP2 Study Collaborator Group. MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nat Med. 2023 Oct;29(10):2473-2480. doi: 10.1038/s41591-023-02565-4. Epub 2023 Sep 14.

  PMID: 37709999 BACKGROUND

• Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, Bird C, Blom RE, Brennan C, Brusch D, Burke L, Campbell-Coker K, Carhart-Harris R, Cattell J, Daniel A, DeBattista C, Dunlop BW, Eisen K, Feifel D, Forbes M, Haumann HM, Hellerstein DJ, Hoppe AI, Husain MI, Jelen LA, Kamphuis J, Kawasaki J, Kelly JR, Key RE, Kishon R, Knatz Peck S, Knight G, Koolen MHB, Lean M, Licht RW, Maples-Keller JL, Mars J, Marwood L, McElhiney MC, Miller TL, Mirow A, Mistry S, Mletzko-Crowe T, Modlin LN, Nielsen RE, Nielson EM, Offerhaus SR, O'Keane V, Palenicek T, Printz D, Rademaker MC, van Reemst A, Reinholdt F, Repantis D, Rucker J, Rudow S, Ruffell S, Rush AJ, Schoevers RA, Seynaeve M, Shao S, Soares JC, Somers M, Stansfield SC, Sterling D, Strockis A, Tsai J, Visser L, Wahba M, Williams S, Young AH, Ywema P, Zisook S, Malievskaia E. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med. 2022 Nov 3;387(18):1637-1648. doi: 10.1056/NEJMoa2206443.

  PMID: 36322843 BACKGROUND

• Reiff CM, Richman EE, Nemeroff CB, Carpenter LL, Widge AS, Rodriguez CI, Kalin NH, McDonald WM; the Work Group on Biomarkers and Novel Treatments, a Division of the American Psychiatric Association Council of Research. Psychedelics and Psychedelic-Assisted Psychotherapy. Am J Psychiatry. 2020 May 1;177(5):391-410. doi: 10.1176/appi.ajp.2019.19010035. Epub 2020 Feb 26.

  PMID: 32098487 BACKGROUND

• Johnson MW, Griffiths RR. Potential Therapeutic Effects of Psilocybin. Neurotherapeutics. 2017 Jul;14(3):734-740. doi: 10.1007/s13311-017-0542-y.

  PMID: 28585222 BACKGROUND

• Steenkamp MM, Litz BT, Hoge CW, Marmar CR. Psychotherapy for Military-Related PTSD: A Review of Randomized Clinical Trials. JAMA. 2015 Aug 4;314(5):489-500. doi: 10.1001/jama.2015.8370.

  PMID: 26241600 BACKGROUND

MeSH Terms

Conditions

Combat Disorders; Stress Disorders, Post-Traumatic

Interventions

Psilocybin; Pharmaceutical Preparations

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Talma Hendler, Prof.

  Tel Aviv University and Tel Aviv Sourasky Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ayelet Or-Borichev, PhD

CONTACT

+972507941243; ayeletorb@gmail.com

Jackob Nimrod Keynan, PhD

CONTACT

+972544509968; nimrodke1@gmail.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: This is an open-label, single-group pilot study in which all participants receive the same intervention. The study follows a structured clinical protocol combining trauma-focused psychotherapy with psilocybin administration. The protocol includes a baseline clinical assessment conducted remotely, followed by two preparatory psychotherapy sessions. Participants then undergo two psilocybin dosing sessions (15 mg and 25 mg), each followed by a series of integration psychotherapy sessions. The study protocol comprises a total of ten in-person study sessions. Clinical assessments include baseline evaluation using self-report questionnaires and the Clinician-Administered PTSD Scale (CAPS-5). An immediate post-treatment assessment is conducted using self-report questionnaires, followed by a clinical assessment using CAPS-5 at 30 days post-intervention.

Study Record Dates

• First Submitted: July 14, 2026
• First Posted: July 30, 2026
• Study Start: July 22, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 30, 2026

Record last verified: 2026-07

Locations

IL (1)