Randomized, Double-blind, Controlled of MDMA-assisted Psychotherapy in 12 Subjects With PTSD

Post traumatic stress disorder (PTSD) is a debilitating disorder that can develop after people experience a traumatic event, such as a rape, car accident or other life threatening event. PTSD is a worldwide health problem. PTSD is treated with psychotherapy or drugs, but these treatments do not help everyone. 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy might be a potential treatment for PTSD. MDMA is the active ingredient in ecstasy. Before it was made illegal, some psychotherapists combined MDMA with psychotherapy to help treat people with psychological problems, including PTSD.

This is a Phase 2 randomized, dose comparison, double-blind study to assess safety and efficacy of manualized MDMA-assisted psychotherapy in treating chronic, treatment-resistant PTSD. Seven subjects will be randomized to receive full dose MDMA (full dose condition) and five subjects will receive a comparator (comparator condition), with an optional supplemental half-dose available 1.5 to 2.5 hours after the initial dose. Global Clinician-Administered PTSD Scale (CAPS) score one month after two sessions of MDMA-assisted psychotherapy is the primary outcome measure.

MDMA or comparator will be administered in two blinded experimental sessions lasting up to eight hours and scheduled three to five weeks apart.

The will last up to one and a half years, including approximately three to five months of psychotherapy, and a long-term follow up visit scheduled a year after the final experimental session. Study subjects will have a medical and psychiatric examination to assess eligibility for enrollment. Once in the study, they will see the same male and female psychotherapist for the entire study. The subject will learn more about MDMA-assisted psychotherapy and the investigators will learn more about the subject during three preparatory sessions occurring before the first experimental session. During experimental sessions, subjects will receive an initial dose of either full dose MDMA or placebo along with psychotherapy, and one and a half to two and a half hours later, the subject may have a supplemental half the size of the initial dose. Vital signs and psychological distress will be measured throughout the experimental session. There will be three integrative psychotherapy sessions after each experimental session, including one occurring the day after an experimental session. Subjects will express, understand and connect any of their thoughts or feelings about PTSD symptoms and their causes, and they will discuss their experience during experimental sessions with the therapists.

Subjects will learn the dose of MDMA they received one month after the second MDMA-assisted psychotherapy session. Subjects who received full dose will complete Stage 1, with a third open-label session, and subjects who received comparator dose MDMA will go on to Stage 2, an open label period of the study that is nearly identical to stage 1, but with one instead of three preparatory sessions and one of two active doses of MDMA used in all three experimental sessions.

Symptoms of PTSD, depression, dissociation, general psychological well-being, sleep quality and potential positive effects of experiencing traumatic events will be measured in all subjects at baseline, one month after the second experimental session and 12 months after their final experimental session, and any subjects reporting pain or tinnitus at the start of the study will record these symptoms throughout the study.Subjects who received the full dose and go on to the third experimental session will complete questionnaires and measures of PTSD and other symptoms two months after the third experimental session. Subjects who received comparator dose MDMA will be tested one month after their second Stage 2 experimental session and two months after the third experimental session. Measures of cognitive function will be given to subjects in Stage two months after their third experimental session, and to Stage 2 subjects two months after their third Stage 2 session. People will also complete measures of their experience of the experimental session soon after each experimental session. At least 12 months after their final Stage 1 or Stage 2 session, measures of PTSD symptoms, other symptoms, sleep quality, general well-being and and post traumatic growth will be assessed again, and subjects will complete a questionnaire on the benefits and harms of study participation and other life events and views related to study participation.

This study will compare the effects of MDMA-assisted psychotherapy with comparator versus full dose MDMA, and it will also assess the duration of any changes in symptoms a year after MDMA-assisted psychotherapy.