MDMA-AT for PTSD in Young Adults With Childhood Trauma

Inclusion criteria

Demographic and Participant Information

• Between the ages of 18-26 years old upon signing the written consent form
• Proficient in speaking and reading English.
• Capable of providing informed consent.
• Is able to swallow pills.
• Willing and able to be contacted by phone throughout the study
• Resides in the United States
• Meets DSM-5 criteria for PTSD with sufficient severity assessed at study screening
• History of index Criterion A trauma that occurred in childhood
• Must agree to inform the research team within 48 hours of any emerging or new medical conditions and/or procedures
• Must provide an emergency contact
• Has someone to drive them home after each MDMA-AT session (or agrees to take a taxi/rideshare while accompanied by a close other)
• Agree not to drive for 24 hours after each MDMA-AT session
• Agree to return to place of residence immediately after each MDMA-AT session, and stay there until the next morning
• Has a trusted close other who is at least 18 years of age that agrees to stay with them throughout the night until the morning after each MDMA-AT session, and is willing to attend the ICF meeting and co-sign the ICF
• Agree to not participate in any other interventional clinical trials from baseline to the primary study endpoint
• Is willing and able to refrain from taking any psychiatric medications during the study period.
• Agrees to abstain from other medications (e.g., over the counter, PRN medications, etc) unless approval from PI has been obtained

If able to become pregnant:

• Must have a negative pregnancy screen during study screening and on the morning of each MDMA-AT session;
• Must agree to use adequate birth control for the duration of participation
• Has a primary care provider (PCP)
• Has a regular outpatient mental health treater (e.g., psychiatrist, psychologist) that will resume care for the participant following completion or termination of study participation

Exclusion criteria

• Recently attempted suicide or engaged in high risk self-injury or is otherwise assessed to be at imminent risk of suicide by study staff
• In the opinion of the PI, would present a serious risk to others as established through study screening measures or clinical observations.
• Meets DSM-5 criteria for any current substance use disorder, other than alcohol, cannabis, or nicotine use disorder
• For cannabis use and alcohol use disorders without physiological dependence, must agree to be abstinent from alcohol and cannabis for one week prior to and following each MDMA-AT session.
• Meets DSM-5 criteria for current cannabis or alcohol use disorder with physiological dependence, or physiological dependence cannot be determined
• Meets other DSM-5 criteria for serious mental illness, as assessed by the DART or through clinical interviews or observations
• Has a current restrictive eating disorder with current low body-mass index, or any eating disorder with active purging, currently, or in the 3 months prior to enrollment
• Diagnosed major neurodevelopmental or neurological disorder.
• Scaled score on the Test of Premorbid Functioning that is suggestive of possible cognitive impairment.
• Has used MDMA in the month prior to enrollment
• Has used MDMA excessively in the past
• Has participated in a previous MDMA-AT for PTSD clinical trial
• Has hypersensitivity to any ingredient of the Investigational Product
• Requires ongoing concomitant therapy with a psychiatric drug, excluding gabapentin.
• Is currently receiving trauma-focused psychotherapy and unwilling or unable to put treatment on hold for the duration of active study participation
• Has received Electroconvulsive Therapy (ECT) within 12 weeks of enrollment.
• Has received ketamine infusions and/or ketamine-assisted therapy in the 8 weeks prior to enrolment
• Requires the use of opiates for pain management
• Currently on methadone maintenance treatment
• Has symptomatic liver disease or significant liver enzyme elevation
• Weighs less than 48 kg (105 lbs)
• History of concussion with loss of consciousness ≥ 24 hours or traumatic brain injury
• History of hyponatremia or hyperthermia.
• Any medical condition that could make receiving a sympathomimetic drug harmful because of increases in blood pressure and heart rate.
• Uncontrolled hypertension
• History of arrythmia (e.g., atrial or ventricular arrhythmia) at any time, other than occasional premature atrial contractions (PACs) or premature ventricular contractions (PVCs) in the absence of ischemic heart disease, within 12 months of screening.
• History of tachycardia or cardiac disorder.
• Has Wolff-Parkinson-White syndrome or any other accessory pathway that has not been successfully eliminated by ablation.
• marked Baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval >450 milliseconds (ms) in males and >460 ms in females corrected by Fridericia's formula). For transgender or non- binary participants, QTc interval will be evaluated based on sex assigned at birth, unless the participant has been on hormonal treatment for five or more years.
• History of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
• Requires use of concomitant medications that prolong the QT/QTc interval
• Standard MRI contraindications
• Is pregnant or nursing, planning to become pregnant during the course of the study, or is able to become pregnant and not practicing an effective means of birth control.
• In the opinion of the PI, participant's current place of residence is unstable
• Is currently engaged in compensation litigation whereby financial gain would be achieved from prolonged psychiatric symptoms
• Requires a legally authorized representative to provide informed consent
• In the opinion of the study PI, is not able to adhere to the requirements for procedures, attendance and timing of visits, and observe limits regarding study staff time and support
• Is participating in another interventional clinical trial at any point from study screening to the primary study endpoint (i.e., post-treatment visit)
• Does not reside in the US
• Substantial colorblindness sufficient to impede performance on the fMRI tasks