Group vs Individual MDMA-Assisted Therapy for PTSD After the October 7, 2023 Events

NCT07469098 | Recruiting Phase 2 DMC

• 1 other identifier: SHEBA-0894-23-RA-CTIL
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to evaluate the safety, tolerability and effectiveness of group-based MDMA-assisted therapy compared to individual MDMA-assisted therapy in participants with PTSD, who were diagnosed following the events of 7 October 2023. The main questions it aims to answer are: safety and tolerability? effectiveness? Researchers will compare group-based MDMA-assisted therapy to individual MDMA-assisted therapy to see if group-based MDMA-assisted therapy is not inferior to individual MDMA-assisted therapy, in terms of safety and effectiveness. Participants will be randomized to one of two study arms: group-based MDMA-assisted therapy or individual MDMA-assisted therapy receive MDMA HCl administered orally in a divided dose. Participate in preparatory sessions, MDMA dosing sessions, and integration sessions. Be monitored for adverse events and suicidality (C-SSRS). Be monitored by an external Data Safety Monitoring Board (DSMB).

Conditions

PTSD

Outcome Measures

Primary Outcomes (2)

• Change in PTSD symptoms as measured by CAPS-5

  Change from baseline in PTSD symptoms as measured by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5).

  Baseline to end-of-treatment visit (Week 17 in the GMAT; Week 13 in the IMAT)

• Change in PTSD symptoms as measured by PCL-5

  Change from baseline in PTSD symptoms as measured by the PTSD Checklist for DSM-5 (PCL-5).

  Baseline to end-of-treatment visit (Week 17 in the GMAT; Week 13 in the IMAT)

Secondary Outcomes (6)

• Safety and tolerability

  From baseline through end-of-study visit (Week 17 in the GMAT; Week 13 in the IMAT)

• Suicidal ideation and behavior assessed with C-SSRS

  From baseline through end-of-study visit Week 17 in the GMAT; Week 13 in the IMAT), assessed throughout the treatment period

• Change in systolic and diastolic blood pressure

  From pre-IP administration to end of each Experimental Session (Weeks 6, 10, and 14 in the GMAT arm; Weeks 4, 7, and 10 in the IMAT arm)

• Change in heart rate

  From pre-IP administration to end of each Experimental Session (Weeks 6, 10, and 14 in the GMAT arm; Weeks 4, 7, and 10 in the IMAT arm)

• Change in respiratory rate

  From pre-IP administration to end of each Experimental Session (Weeks 6, 10, and 14 in the GMAT arm; Weeks 4, 7, and 10 in the IMAT arm)

Study Arms (2)

Group-based MDMA-assisted therapy

EXPERIMENTAL

Participants will receive group-based MDMA-assisted therapy (up to 7 participants per group). Each group will include participants with the same type of trauma. MDMA HCl will be administered orally during dosing sessions in a divided dose, with a supplemental dose administered 1.5 to 2 hours after the initial dose. Participants will attend preparatory sessions and integration sessions according to the protocol.

Drug: MDMA HCl

Individual MDMA-assisted therapy

EXPERIMENTAL

Participants will receive individual MDMA-assisted therapy. MDMA HCl will be administered orally during dosing sessions in a divided dose, with a supplemental dose administered 1.5 to 2 hours after the initial dose. Participants will attend preparatory sessions and integration sessions according to the protocol.

Drug: MDMA HCl

Interventions

MDMA HCl DRUG

MDMA HCl will be administered orally during dosing sessions in a divided dose. In the first dosing session, participants will receive 80 mg MDMA HCl with a supplemental dose of 40 mg administered 1.5 to 2 hours after the initial dose. In the second and third dosing sessions, participants will receive 120 mg MDMA HCl with a supplemental dose of 60 mg administered 1.5 to 2 hours after the initial dose.

Group-based MDMA-assisted therapy; Individual MDMA-assisted therapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are at least 18 years old.
• At Screening, meet DSM-5 criteria for current PTSD that has been diagnosed past 7/10/23 and the events following.
• At Screening, have at least moderate PTSD symptoms in the last month, based on PCL-5 total score of 36 or greater, conducted by certified Study coordinators.
• Are fluent in speaking and reading the predominantly used or recognized language of the study site (Hebrew).
• Are able to swallow pills.
• Participant where in psychotherapy prior to the study. If the participant is still in psychotherapy during study enrollment, they consent to continue therapy during the study and provide consent for the investigator to communicate with the therapist as needed.
• Must provide a contact (relative, spouse, close friend, or other support person) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal or unreachable.
• Must agree to inform the investigators within 48 hours of any medical conditions and procedures.
• Agree to the following lifestyle modifications (see lifestyle modifications section) : comply with requirements for fasting and refraining from certain medications prior to Experimental Sessions, not participate in any other interventional clinical trials during the duration of the study, remain overnight at the study site after each Experimental Session and be driven home after, and commit to medication dosing, therapy, and study procedures.
• If able to become pregnant (i.e. assigned female at birth, fertile, following menarche and until becoming post-menopausal unless permanently sterile), must have a highly sensitive negative pregnancy test at study entry and prior to each Experimental Session, and must agree to use adequate birth control through 10 days after the last Experimental Session. Adequate birth control methods include intrauterine device (IUD), injected, implanted, intravaginal, or transdermal hormonal methods, abstinence, oral hormones plus a barrier contraception, vasectomized sole partner, or double barrier contraception. Two forms of contraception are required with any barrier method or oral hormones (i.e. condom plus diaphragm, condom or diaphragm plus spermicide, oral hormonal contraceptives plus spermicide or condom).
• Holds a permanent address in the next 6 months.
• Medical History
• May have well-controlled hypertension that has been successfully treated with anti-hypertensive medicines, if they pass additional screening to rule out underlying cardiovascular disease.
• May have asymptomatic Hepatitis C virus (HCV) that has previously undergone evaluation and treatment as needed.
• May have alcohol or substance use disorder if the participant is not in withdrawal or requiring detox. Participants must have a plan, agreed upon by the investigator, therapy team, and study physician, to reduce use of alcohol or other substances and to manage symptoms without self-medicating. Enrollment will require that, in the judgment of the investigator, therapy team, and study physician, the plan for decreasing substance use is realistic and has a good chance of succeeding in order to prevent substance use from impacting the safety or efficacy of the investigational treatment.

You may not qualify if:

• Are not able to give adequate informed consent.
• Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the investigator or study clinician, contraindicates participation in the study.
• Active military duty expected in the following 12 months.
• Death of a close person in the past 6 months.
• Psychiatric History
• Have received Electroconvulsive Therapy, Transcranial Magnetic Stimulation, or Ketamine Therapy within 12 weeks of enrollment.
• Have a history of, or a current diagnosis of schizophrenia, schizoaffective disorder, major depressive disorder with psychotic features, psychotic disorder, bipolar disorder I or II (with or without psychotic features), or dissociative identity disorder assessed by medical history, investigator interview and the Mini-International Neuropsychiatric Interview (MINI).
• Have a current substance use disorder other than caffeine or nicotine that the investigators, therapy team, and/or study physician judge to be a safety concern for enrollment in the study or that could interfere with the therapeutic process or with other aspects of study participation as assessed by clinical interview per DSM-5 as well as Audit and Dudit questionnaires. Any participant who is not able to agree or adhere to a plan to reduce use and manage symptoms will not be enrolled.
• Have an active illicit (other than cannabis) or prescription drug substance use disorder at any severity within 12 months prior to enrollment.
• Have current Personality Disorders Cluster A (paranoid, schizoid, schizotypal), Cluster B (antisocial, borderline, histrionic, narcissistic), or Cluster C (avoidant, dependent, obsessive-compulsive) assessed via SCID-5-PD.
• Suicidal ideation score of 4 or greater within the last 6 months of the assessment at a frequency of once a week or more.
• Suicidal ideation score of 5 within the last 6 months of the assessment.
• Any suicidal behavior, including suicide attempts or preparatory acts, within the last 6 months of the assessment. Participants with non-suicidal self-injurious behavior may be included if approved by the study physician.
• Would present a serious risk to others as established through clinical interview and contact with treating psychiatrist.
• Have a blood or needle phobia that interferes with obtaining necessary blood work.

Sponsors & Collaborators

• Sheba Medical Center: lead

Study Sites (2)

Mental Health Medical Center Beer Sheva

Beersheba, Israel

RECRUITING

Lev-Hasharon Mental Health Medical Center

Pardesiyya, Israel

RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

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

Study Officials

• Revital Amiaz

  Sheba Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Revital Amiaz

CONTACT

972542378757; revital.amiaz@sheba.health.gov.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Participants will be randomized in a 1:3 ratio (individual MDMA-assisted therapy : group-based MDMA-assisted therapy).

Study Record Dates

• First Submitted: February 10, 2026
• First Posted: March 13, 2026
• Study Start: December 24, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): March 31, 2029
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

IL (2)