Dose-Response Study of MDMA-assisted Psychotherapy in People With PTSD
Condition: Posttraumatic Stress Disorder
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Intervention: Comparative-dose (40mg) MDMA; Active Dose 2 (100 mg) MDMA; Active Dose 1 (125 mg) MDMA; Psychotherapy
Intervention description: An initial comparator-dose of 40 mg MDMA orally given at the start of two separate psychotherapy sessions scheduled 3 to 5 weeks apart, with the initial dose possibly followed 1.5 to 2.5 hours later by a supplemental dose half the size of the initial dose (20 mg MDMA).; An initial dose of full-dose 100 mg MDMA orally given at the start of two separate psychotherapy sessions scheduled 3 to 5 weeks apart, with the initial dose possibly followed 1.5 to 2.5 hours later by a supplemental dose half the size of the initial dose (50 mg MDMA).; An initial dose of full-dose 125 mg MDMA orally given at the start of two separate psychotherapy sessions scheduled 3 to 5 weeks apart, with the initial dose possibly followed 1.5 to 2.5 hours later by a supplemental dose half the size of the initial dose (62.5 mg MDMA).; Psychotherapy conducted throughout experimental sessions.
Intervention MeSH terms: N-Methyl-3,4-methylenedioxyamphetamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MDMA; Posttraumatic stress disorder; sleep; Depression; Safety

Summary:

      Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder that can develop
      after a traumatic life experience that severely reduces quality of life. This Phase 2 pilot
      study examined the safety and efficacy of MDMA-assisted psychotherapy in 23 subjects with
      chronic, treatment-resistant posttraumatic stress disorder (PTSD). This study is part of a
      global series of Phase 2 pilot clinical trials. This randomized, double-blind, dose response
      study assessed two active doses of MDMA, 100 mg and 125 mg, to a comparator dose of MDMA (40
      mg) during psychotherapy sessions. The initial dose was followed 1.5 to 2.5 hours later by an
      optional supplemental dose of MDMA that was half the size of the first dose. MDMA was
      administered in two experimental sessions lasting up to eight hours and scheduled three to
      five weeks apart. Subjects were prepared for MDMA-assisted psychotherapy prior to the first
      session in three preparatory sessions, and worked with the same pair of therapists throughout
      the study. After each MDMA-assisted psychotherapy session, subjects had three integrative
      sessions with their therapist team to process and understand their experience.

      This study assessed the change in symptoms of PTSD, as measured by the Clinical Administered
      PTSD Scale (CAPS) [Blake et al., 1995], as well as symptoms of depression, as measured by the
      Beck Depression Inventory II (BDI-II) [Beck, A.T. and R.A, 1984; Beck, A.T., et al., 1996]
      from baseline enrollment to one month after the second MDMA-assisted psychotherapy session
      (primary endpoint).

      Participants who received the comparator dose of MDMA (40 mg) were given the option to enroll
      in Stage 2, where they underwent three open-label MDMA-assisted psychotherapy sessions with
      an active dose of MDMA. People who received either of the active doses of MDMA in Stage 1 had
      a third MDMA-assisted psychotherapy session with another active dose of MDMA.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosed with chronic PTSD for six months or longer.

          -  Have a CAPS score showing moderate to severe PTSD symptoms.

          -  At least one unsuccessful attempt at treatment for PTSD either with talk therapy or
             with drugs, or discontinuing treatment because of inability to tolerate psychotherapy
             or drug therapy.

          -  Are at least 18 years old.

          -  Must be generally healthy.

          -  Are willing to refrain from taking any psychiatric medications during the study
             period.

          -  Willing to follow restrictions and guidelines concerning consumption of food,
             beverages or nicotine the night before and just prior to each MDMA session.

          -  Willing to remain overnight at the study site.

          -  Are willing to be driven home after experimental sessions either by a driver they
             arrange, a taxi, or study personnel.

          -  Are willing to be contacted via telephone by study personnel.

          -  If of child-bearing age, must have a negative pregnancy and agree to use an effective
             form of birth control.

          -  Must provide a personal contact who is willing to be reached in case of emergency.

          -  Agree to let the investigators know within 48 hours of any planned medical
             interventions.

          -  Are proficient in reading and speaking English.

          -  Agree to have all psychotherapy sessions recorded.

          -  Agree not to participate in any other interventional clinical trials during the course
             of the study.

        Exclusion Criteria:

          -  Are pregnant or nursing, or if of child-bearing age and do not use an effective means
             of birth control.

          -  Weigh less than 48 kg.

          -  Are abusing illegal drugs.

          -  Are unable to give adequate informed consent.

          -  Upon review of past and current drugs/medication, must not be on or have taken a
             medication that is exclusionary.

          -  Upon review of medical or psychiatric history, must not have any current or past
             diagnosis that would be considered a risk to participation in the study.