Post Traumatic Stress DisorderPhase 2NCT05732155
Preliminary Effectiveness of Hybrid Individual and Group MDMA-assisted Therapy for War-related PTSD
A Phase 2 study testing methylenedioxymethamphetamine in people with Post Traumatic Stress Disorder and MDMA ('Ecstasy'), run by Guy Schusheim at 1 site in Israel.
Trial summary
The overall objective of this study is to use standard clinical measures to explore the safety and preliminary effectiveness of open-label MDMA-assisted therapy with a flexible dose of methylenedioxymethamphetaminel, in participants with war-related Post traumatic Stress Disorder, in a hybrid individual and group… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Post Traumatic Stress Disorder, MDMA ('Ecstasy')
- What is being tested?
- methylenedioxymethamphetamine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Jun 2023to 1 Jul 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Experienced war-related trauma.
- Fluent in speaking and reading Hebrew.
- Able to swallow capsules.
- Willing to have study visits, including MDMA experimental sessions and non-drug psychotherapy sessions, audio- and/or video-recorded as specified by the protocol.
- Able to identify a relative, spouse, close friend, or other support person who can be contacted by the investigators if the participant becomes suicidal or cannot be reached.
- Agrees to inform the investigators within 48 hours of relevant medical conditions or procedures.
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- Agrees to comply with study requirements, including fasting and medication restrictions before experimental sessions, refraining from participation in other interventional clinical trials during the study, remaining overnight at the study site after each experimental session, arranging accompanied transportation after discharge, and complying with study medication, psychotherapy, and assessment procedures.
- At screening, meets DSM-5 criteria for current PTSD of the protocol-specified minimum duration.
- At screening, has at least moderate PTSD symptom severity, defined as a CAPS-5 total score of 28 or greater.
Who cannot join
- Unable to provide adequate informed consent.
- Use of Ecstasy or material represented as containing MDMA more than 10 times during the previous 10 years, or any such use within 6 months before the first experimental session.
- Previous participation in a MAPS-sponsored MDMA clinical trial.
- Any current medical, psychiatric, psychosocial, or other condition that, in the judgment of the investigator or study physician, could interfere with safe or effective participation.
- Known sensitivity or allergy to MDMA or another study intervention that, in the judgment of the sponsor-investigator or study clinician, contraindicates participation.
- Electroconvulsive therapy within 12 weeks before enrollment.
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- Current or lifetime primary psychotic disorder.
- Current eating disorder involving active purging, as assessed by the MINI and clinical interview.
- Current major depressive disorder with psychotic features, as assessed by the MINI.
- Current alcohol or substance use disorder judged by the investigators, therapy team, or study physician to represent a safety concern.
- Active illicit-drug or prescription-drug substance use disorder, other than caffeine or nicotine use disorder, within 12 months before enrollment, as defined by the protocol.
- Current personality disorder meeting the protocol-specified exclusion criteria.
- Current serious suicide risk.
- Requirement for ongoing treatment with a psychiatric medication that cannot be discontinued or is not permitted under the protocol, except as specified in the concomitant-medication provisions.
- Medical condition for which exposure to a sympathomimetic drug or associated increases in blood pressure or heart rate would pose an unacceptable risk.
- Uncontrolled hypertension, defined according to the protocol as blood pressure of 140/90 mmHg or higher on three separate occasions.
- History of ventricular arrhythmia other than premature ventricular contractions in the absence of ischemic heart disease.
- Wolff-Parkinson-White syndrome or another accessory conduction pathway that has not been successfully treated by ablation.
- History of clinically significant arrhythmia within 12 months before screening, other than premature atrial contractions or occasional premature ventricular contractions in the absence of ischemic heart disease.
- Baseline QTc prolongation greater than 450 ms in males or greater than 460 ms in females, corrected using Fridericia's formula.
- Additional risk factors for torsade de pointes, including heart failure, hypokalemia, or a family history of long-QT syndrome.
- Requirement for concomitant medications that prolong the QT/QTc interval during experimental sessions.
- Symptomatic liver disease or clinically significant liver-enzyme elevations.
- History of hyponatremia or hyperthermia.
- Body weight below 48 kg.
- Ketamine-assisted therapy or ketamine use within 12 weeks before enrollment.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site, 1 recruiting
- Recruiting
Emek medical center
Afula, 1910500
Gilat Ron Avraham, 0528495336, gilataavraham@gmail.com
About this study
The overall objective of this study is to use standard clinical measures to explore the safety and preliminary effectiveness of open-label MDMA-assisted therapy with a flexible dose of methylenedioxymethamphetaminel, in participants with war-related Post traumatic Stress Disorder, in a hybrid individual and group treatment protocol.
The overall safety objective is to assess the severity, incidence, and frequency of AEs, AEs of Special Interest (AESIs), and Serious Adverse Events (SAEs), concomitant medication use, suicidal ideation and behavior and vital signs .
Read the detailed description
This is a single-site, two-arm, open-label, nonrandomized study evaluating the safety and preliminary effectiveness of MDMA-assisted therapy (MDMA-AT) in participants diagnosed with posttraumatic stress disorder (PTSD). The study will enroll at least 30 participants in the MDMA-AT arm. A treatment-as-usual (TAU) comparison arm of approximately 30 participants will be recruited separately. Therapy teams delivering MDMA-AT have been trained in the MAPS therapeutic approach.
The MDMA-AT intervention lasts approximately 18 weeks and includes an initial individual phase followed by a group phase. Participants receive three MDMA experimental sessions: two individual experimental sessions and one group experimental session. MDMA hydrochloride is administered during each experimental session, with a planned supplemental half-dose unless tolerability concerns arise or the participant declines. Experimental sessions last approximately 8 hours and are followed by an overnight stay.
Following screening, informed consent, eligibility assessment, baseline assessment, and enrollment, participants begin a preparatory period. This includes three 90-minute individual non-drug preparatory sessions (V1-V3), during which participants are prepared for the therapeutic process and experimental sessions. Medication tapering, when required, is completed according to the study protocol.
The individual treatment phase includes two individual MDMA experimental sessions (V4 and V8). Each experimental session is followed by three individual non-drug integration sessions. The first integration session takes place on the morning after the experimental session, with subsequent integration sessions occurring over the following weeks. Thus, V4 is followed by V5-V7, and V8 is followed by V9-V11. The PCL-5 is also administered during the treatment period as specified in the assessment schedule.
After completion of the individual phase, participants transition to the group phase. Because participants complete their individual treatment schedules on different dates, an interval is permitted before initiation of the group phase to allow members of each treatment group to begin group treatment together. To minimize variability in this interval, participants intended for the same group are scheduled to begin the individual treatment phase within approximately the same time period. Scheduling may nevertheless be adjusted because of recruitment, screening, staff availability, medication tapering, and other operational considerations.
The group phase begins with two non-drug group preparatory sessions (V12-V13), intended to introduce participants to the group format, facilitate acquaintance among group members, and discuss individual goals and expectations. Participants then complete one group MDMA experimental session (V14). During the main drug-effect period, participants engage primarily in inward-focused therapeutic work, with therapist support available as needed. The group experimental session is followed by three group integration sessions (V15-V17), with V15 occurring on the morning after V14 and subsequent sessions occurring over the following weeks.
The primary clinical outcome is change in Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) total score from baseline to the post-treatment assessment at V18. V18 also serves as the final study visit for the active treatment period. Additional CAPS-5 follow-up assessments are conducted at 3, 6, and 12 months following completion of the treatment protocol. Safety is monitored throughout treatment and follow-up according to study procedures.
The TAU comparison arm includes approximately 30 participants with PTSD receiving routine care through the psychiatric clinic of the Israeli Ministry of Defense at Emek Medical Center. Participants in this arm continue their usual psychiatric and psychotherapeutic care and do not receive MDMA as part of the study. Outcomes from this cohort will be used as an exploratory longitudinal comparator for the MDMA-AT cohort.
- Conditions
- Post Traumatic Stress Disorder, MDMA ('Ecstasy')
- Being tested
- methylenedioxymethamphetamine
- Keywords
- post traumatic stress disorder, PTSD, MDMA, Psychedelics, Group
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methylenedioxymethamphetamineDrug
Also called MDMA
Participants in the experimental arm receive MDMA hydrochloride during three approximately 8-hour experimental sessions conducted within a manualized MDMA-assisted therapy protocol. Two sessions are delivered individually and one is delivered in a group setting. Each session includes an initial dose of MDMA hydrochloride followed by a planned supplemental half-dose approximately two hours later, unless the participant declines or tolerability concerns arise. MDMA administration is embedded within preparatory and integration psychotherapy delivered according to the study protocol.
| Study group | Role | What they receive |
|---|---|---|
| MDMA-assisted therapy | Experimental | Participants receive an approximately 18-week MDMA-assisted therapy intervention combining individual and group treatment. The intervention includes three individual preparatory sessions; two individual MDMA-assisted sessions, each followed by three individual integration sessions; two group preparatory sessions; one group MDMA-assisted session followed by three group integration sessions; and a final individual integration and termination session. Receives: Drug: methylenedioxymethamphetamine |
| Treatment as usual control | No intervention | The nonrandomized treatment-as-usual (TAU) comparison cohort will comprise participants with war-related PTSD recruited concurrently from the same target population. Participants will receive no protocol-directed MDMA-assisted intervention and will continue any routine psychiatric, psychological, or other clinical care available to them outside the study. Eligibility criteria for the TAU cohort are less restrictive than those applied to the MDMA-assisted therapy arm. Study assessments will be conducted at baseline and approximately 3.5 months later, approximating the baseline-to-post-treatment interval in the MDMA-assisted therapy arm. Participants will receive US$500 for study participation. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from pre-treatment baseline to post-treatment in CAPS-5 total score
The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a clinician-administered interview assessing PTSD symptom severity. The primary outcome is change in CAPS-5 total severity score from baseline to the post-treatment outcome assessment at V18. Higher CAPS-5 scores indicate greater PTSD symptom severity; therefore, a decrease from baseline indicates improvement. This outcome will be assessed in participants assigned to both the experimental MDMA-assisted therapy arm and the treatment-as-usual arm.
Measured: From baseline to V18, approximately 18 weeks
Secondary outcomes (3)
Change in CAPS-5 total score from baseline and from post-intervention to 3, 6, and 12 months follow-up assessments
The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a clinician-administered interview assessing PTSD symptom severity. This secondary outcome evaluates change in CAPS-5 total severity score from the pre-treatment baseline assessment to the 3-, 6-, and 12-month follow-up assessments to evaluate the durability of treatment-related changes in PTSD symptoms. Higher CAPS-5 scores indicate greater PTSD symptom severity; therefore, a decrease from baseline indicates improvement. Follow-up assessments will be conducted only in participants assigned to the experimental MDMA-assisted therapy arm.
Measured: Baseline and 3, 6, and 12 months after completion of the treatment protocol.
Change in self-reported anxiety symptoms assessed with the Generalized Anxiety Disorder Scale (GAD-7)
Change in self-reported anxiety symptoms will be assessed using the seven-item Generalized Anxiety Disorder Scale (GAD-7). GAD-7 total scores range from 0 to 21, with higher scores indicating greater symptom severity. Participants in both the experimental MDMA-assisted therapy arm and the treatment-as-usual arm will complete the measure at baseline and post-intervention. Participants in the experimental arm will additionally complete the measure after treatment sessions, except at V5, V9, and V15, which immediately follow the MDMA dosing sessions.
Measured: Baseline and post-intervention in both study arms; additionally, before treatment sessions in the experimental arm throughout the approximately 18-week treatment period, except at V5, V9, and V15.
Change in self-reported depressive symptoms assessed with the Patient Health Questionnaire (PHQ-9)
Change in self-reported depressive symptoms will be assessed using the nine-item Patient Health Questionnaire (PHQ-9). Total scores range from 0 to 27, with higher scores indicating greater depressive symptom severity. Participants in both the experimental MDMA-assisted therapy arm and the treatment-as-usual arm will complete the measure at baseline and post-intervention. Participants in the experimental arm will additionally complete the measure after treatment sessions, except at V5, V9, and V15, which immediately follow the MDMA dosing sessions.
Measured: Baseline and post-intervention in both study arms; additionally, befor treatment sessions in the experimental arm throughout the approximately 18-week treatment period, except at V5, V9, and V15. The questionnaire assesses symptoms experienced during the
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2023
- Study start1 Jun 2023
- Primary completion1 Jun 2027 (estimated)
- Study completion1 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post Traumatic Stress DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- This is a single-site, two-arm, nonrandomized parallel study. Participants in the experimental arm receive open-label MDMA-assisted therapy consisting of an individual treatment phase followed by a group treatment phase. Participants in the treatment-as-usual comparison arm continue routine psychiatric and psychotherapeutic care and do not receive MDMA through the study. The comparison arm is recruited concurrently but is not randomized or matched to the experimental arm. The primary clinical evaluation is based on within-participant change in the MDMA-assisted therapy arm; between-group comparisons are exploratory.
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guy Schusheim
- Sponsor type
- University, hospital or other
- Collaborators
- Resilient Pharmaceuticals
- Responsible party
- Sponsor-investigator, Guy Schusheim, HaEmek Medical Center, Israel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05732155
- Sponsor's protocol ID
- EMC 00077-21
- Status last verified
- Oct 2026
- First submitted
- 7 Feb 2023
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Participants will be assigned a unique identifier by the sponsor-investigator. Any participant records or datasets that are transferred will contain the identifier only; participant names or any information which would make the participant identifiable will not be transferred.