MDMA-assisted therapy for war-related PTSD — a hybrid individual and group approach

Inclusion Criteria

* 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.
* 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.

Exclusion Criteria

* 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.
* 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.