MDMA-Assisted Psychotherapy in Veterans With Combat-Related, Refractory PTSD

Inclusion Criteria: 1. Participants must be eligible for VA healthcare and currently being treated by VA Loma Linda Healthcare System or VA Long Beach providers 2. Participants must meet DSM 5 criteria for combat-related PTSD (within the past 6 months). PTSD must be defined as treatment-resistant. 3. Participants must have been exposed to combat in the current-era war. 4. Participants must be 18-55 years old. 5. Participants must be generally healthy overall without any significant medical comorbidities (see exclusion criteria). 6. Participants must be willing to refrain from alcohol for 72 hours prior to each MDMA session and be deemed not at risk for significant alcohol withdrawal. 7. Participants must be willing to refrain from taking any psychiatric medications during the study period, including gabapentin or any other anticonvulsants. If they are being treated with psychoactive medications during recruitment, participants must be willing and determined safe (by study physician(s)) to undergo medically-supervised withdrawal from these medications. The medications will be withdrawn in an appropriate fashion to minimize any withdrawal effects. The participants must be able to refrain from starting any new medications during the study period. The only exception to this will be in the case of rescue medications that may be administered in the event of a crisis during the experimental study sessions. 8. Agree that, for one week preceding an MDMA session will refrain from: 1. Taking any herbal supplement (except with prior approval of the research team); 2. Taking any nonprescription medications (with the exception of non-steroidal anti-inflammatory drugs or acetaminophen unless with prior approval of the research team); 3. Taking any prescription medications, with the exception of birth control pills, thyroid hormones or other medications approved by the research team. 9. Are proficient in speaking and reading English. 10. Must meet capacity and consent for treatment. 11. Participants who are engaged in non-PTSD psychotherapy at the time of study screening, may continue to see their therapist during the course of the study. If seeing a non-VA therapist, participants must sign a release for the investigators to communicate directly with their therapist. Subjects may not change therapists, increase the frequency of therapy or commence any new type of therapy until after the evaluation session 2 months after the final experimental session. 12. Participants of childbearing potential and age must have a negative pregnancy test and must agree to use an effective form of birth control during the study period. 13. Participants must be willing to stay overnight at the hospital after each experimental session. 14. Agree to have transportation other than driving themselves home on the day after an MDMA session. 15. Are willing to follow restrictions and guidelines concerning medications, consumption of food, beverages, alcohol, nicotine, or illicit substances. 16. Must provide a contact (relative, spouse, close friend or other caregiver) who is willing and able to be reached by the investigators in the event of a participant becoming suicidal. 17. Must agree to inform the investigators within 48 hours of any medical conditions and procedures. 18. Agree to not participate in any other interventional clinical trials during the duration of this study. 19. Must be able to swallow pills. Exclusion Criteria: 1. Individuals with only non-combat related PTSD. Note: participants will not be excluded for having multiple traumas so long as one of those is combat-related. 2. Participants currently engaged in PTSD psychotherapy. 3. Individuals that are determined medically unstable, unsafe for outpatient detoxification from alcohol, at risk for severe alcohol withdrawal, or unwilling/unable to refrain from alcohol use for at least 72 hours prior to experimental session. 4. Lack a stable living situation or supportive system. 5. Any person unable to give adequate informed consent. 6. Participants of childbearing potential who are pregnant, nursing, or of childbearing age unwilling/unable to practice an effective means of birth control. 7. People with a history of, or a current psychotic disorder, dissociative disorder, bipolar affective disorder or personality disorders. 8. Have a current eating disorder. 9. Have current major depressive disorder with psychotic features. 10. Would present a serious risk to others as established through clinical interview and contact with treating psychiatrist. 11. People with evidence or history of significant hematological, cardiovascular, cerebrovascular, coronary, pulmonary, endocrine, renal, gastrointestinal, hepatic (including LFTs \> 3x upper limit of normal), immunocompromising (examples include recent organ transplant and required to be on immunosuppressants, those with HIV/AIDs, cancer or an autoimmune disease \[i.e., lupus, multiple sclerosis, rheumatoid arthritis\]), neurological disease (including seizure disorder or cognitive impairment). Patients with hypothyroidism who are on adequate and stable thyroid replacement will not be excluded. 12. Have uncontrolled hypertension using the standard criteria of the American Heart Association (values of 140/90 milligrams of Mercury \[mmHg\] or higher assessed on three separate occasions). 13. Have a marked baseline prolongation of QT/QTc interval (e.g., repeated demonstration of a QTc interval \>450 milliseconds \[ms\] for men or \>470 ms for women corrected by Bazett's formula). 14. Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome). 15. Require use of concomitant medications that prolong the QT/QTc interval during Experimental Sessions. 16. Have history of hyponatremia or hyperthermia. 17. People weighing less than 50 kg. 18. People with prior use of "Ecstasy" (illicit drug preparations purported to contain MDMA) more than ten times within the past ten years or at any time within the past 6 months or have previously participated in a MAPS-sponsored MDMA clinical trial. 19. People with ketamine use within the last 12 weeks. 20. People with a serious suicide risk or who are likely to require hospitalization within the course of the study. 21. Individuals who require ongoing treatment with psychoactive medications. 22. Individuals meeting DSM-5 criteria for active substance use disorder for any substance other than caffeine or nicotine assessed. 23. Patients in a residential or intensive outpatient treatment program for substance use will be excluded (patients engaged in self-help program such as after care and relapse prevention and alcoholics-anonymous can be included). 24. Have received Electroconvulsive Therapy (ECT) within 12 weeks of enrollment. 25. Currently engaged in compensation litigation whereby financial gain would be achieved from prolonged symptoms of PTSD or any other psychiatric disorders. 26. Unable to ensure reliable transportation to and from study visits or have unstable housing. 27. Any potential participant presenting current serious suicide risk, as determined through psychiatric interview, responses to questionnaires, and clinical judgment of the investigator will be excluded; however, history of suicide attempts is not an exclusion. Any participant who is likely to require hospitalization related to suicidal ideation and behavior will be excluded. 28. Any potential participant with a C-SSRS Suicidal Ideation score of 5 during the prior six months, or with a suicidal ideation of 4 occurring more frequently than one day per week within the past month will be excluded. 29. Regardless of C-SSRS score, any participant presenting current serious suicide risk, as determined through psychiatric interview, responses to C-SSRS, and clinical judgment of the investigator will be excluded; however, history of suicide attempt is not an exclusion. Any participant who is likely to require hospitalization related to suicidal ideation and behavior will be excluded.