MDMA-assisted Prolonged Exposure Therapy for Comorbid Alcohol Use Disorder and Post-traumatic Stress Disorder

Inclusion Criteria:

1. Both AUD and current PTSD according to the DSM-5 criteria, for 6 months or longer withat least moderate severity, according to investigator judgement and CAPS-5
2. Aged ≥18 years old
3. Adequate cognition and English language skills to give valid consent and completeresearch interviews assessments
4. Willing to give written informed consent
5. Received prior treatment for PTSD or AUD (not including study interventions)
6. Stable housing
7. Able to identify a significant other (such as a family/friend/partner) who couldaccompany them from clinic/provide transport and/or be contacted by the study team ifrequired

Exclusion Criteria:

1. History of, or currently meeting, DSM-5 criteria for:

• current or lifetime psychotic or bipolar disorders, or
• major depression with psychotic features Assessed via Structured ClinicalInterview for DSM-5 - Research Version (SCID-5-RV). Potential participants willbe screened for personality disorders but suitability will then be confirmed byclinical interview given the prevalence of high scores in this comorbidpopulation

2. Pregnant or lactating (contraception must be used and a sensitive pregnancy test willbe performed at baseline and prior to dosing)
3. Significant alcohol withdrawal (current Clinical Institute Withdrawal Assessment forAlcohol [CIWA-Ar] score ≥10, including history of delirium tremens or alcoholwithdrawal seizures).
4. Concurrent use of psychotropic medication (antidepressants and alcohol pharmacotherapyuse considered if assessed by physician and titrated down with 5 half-lives + 1 weekwashout)
5. Use of, and unable or unwilling to cease, any medications likely to interact with MDMAin the opinion of the physicians and investigators during the trial (low dose opiatesare permitted for pain management but not the night before or after MDMA sessions)
6. Substance use disorder other than tobacco (e.g. benzodiazepines, cannabis)
7. Abnormal clinical findings including a history of, or current: cardiac disease and/ordysrhythmia, uncontrolled hypertension or severe hypotension, abnormalelectrocardiogram findings, stroke, liver disease, a history of epilepsy,hyponatraemia, or malignant hyperthermia (controlled hypertension and diabetes type IImay be permitted)
8. Suicide risk according to clinician judgement and responses to Columbia SuicideSeverity Rating Scale-Lifetime (C-SSRS-L) and SCID-5-RV. • Details surrounding any previous attempts >6 months ago will be gathered wherebyattempts related to their trauma/PTSD and/or associated with the use ofpsychostimulants will contribute to risk assessment and guide trial safety measures ifenrolled
9. Clinically unstable systemic medical (e.g., cancer) or psychiatric disorder orcondition that might require hospitalisation that precludes trial participation
10. Regular use of ecstasy (e.g. at least twice in last 6 months, or >10 times within thelast 5 years)
11. Enrolled in any other interventional clinical trials in the previous two months orover the duration of the study