Randomized, Double-blind, Active Placebo-Controlled Pilot Study of MDMA-assisted Psychotherapy in People With Chronic PTSD
Condition: Posttraumatic Stress Disorder (PTSD)
MeSH terms: Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Intervention: Active Placebo Dose MDMA (25 mg); Full Dose MDMA (125 mg); Open Label Full Dose MDMA (125 mg); Psychotherapy
Intervention description: Initial dose of 25 mg MDMA administered orally at the start of each of two psychotherapy sessions, possibly followed by a supplemental dose of 12.5 mg MDMA 1.5 to 2.5 hours later.; Initial dose of 125 mg MDMA administered orally at the start of each of two psychotherapy sessions, possibly followed by a supplemental dose of 62.5 mg MDMA 1.5 to 2.5 hours later.; Initial dose of 125 mg MDMA administered orally at the start of each of two psychotherapy sessions, possibly followed by a supplemental dose of 62.5 mg MDMA 1.5 to 2.5 hours later.; Non-directive psychotherapy will be conducted throughout the study.
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: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MDMA; Posttraumatic stress disorder; PTSD; Israel; psychotherapy

Summary:

      This Phase 2 pilot study assessed the safety and efficacy of MDMA-assisted psychotherapy in
      10 people with chronic, treatment-resistant posttraumatic stress disorder (PTSD), comparing
      the effects of low and full dose MDMA as an adjunct to psychotherapy. The first two subjects
      were enrolled in the open label full dose lead-in with 125 mg of MDMA, followed 1.5 to 2.5
      hours later by a supplemental half-dose of 62.5 mg of MDMA. The remaining eight subjects
      enrolled in Stage 1 of the study and received either an active placebo dose (low dose of 25
      mg MDMA, with a supplemental dose of 12.5 mg MDMA) or a fully active dose of MDMA (125 mg,
      with a supplemental dose of 62.5 mg MDMA) during two experimental psychotherapy session, each
      lasting six to eight hours and scheduled three to five weeks apart. The extent of PTSD
      symptoms was assessed at baseline and two months after the second experimental session using
      the Clinician Administered PTSD Scale (CAPS) [Blake et al., 1995]. Subjects who enrolled in
      Stage 1 and received the active placebo had the opportunity to enroll in Stage 2 of the study
      and complete open-label experimental sessions with the fully active dose of MDMA on the same
      schedule as Stage 1.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosed with chronic PTSD with a duration of 6 months or longer.

          -  Have a CAPS score showing moderate to severe symptoms.

          -  Had at least one unsuccessful attempt at treatment for PTSD, either with talk therapy
             or with drugs, or stopped treatment because of inability to tolerate psychotherapy or
             drug therapy.

          -  Are at least 18 years old.

          -  Generally healthy.

          -  Must sign a medical release for the investigators to communicate directly with their
             therapist and doctors.

          -  Are willing to refrain from taking any psychiatric medications during the study
             period.

          -  Agree that, one week before the MDMA session, will refrain from taking all below
             unless with prior approval of research team: herbal supplements, nonprescription
             medications (with the exception of nonsteroidal anti-inflammatory drugs or
             acetaminophen, any prescription medications, with the exception of birth control
             pills, thyroid hormone, or other medications;

          -  Are willing to follow restrictions and guidelines concerning consumption of food,
             beverages. and nicotine the night before and just prior to each experimental session.

          -  Are willing to remain overnight at the study site.

          -  Are willing to be contacted via telephone for all necessary telephone contacts.

          -  Must have a negative pregnancy test if able to bear children, and agree to use an
             effective form of birth control.

          -  Agree not to participate in any other clinical trial for the duration of this clinical
             trial, including the follow-up period.

          -  Are proficient in speaking and reading Hebrew.

          -  Agree to have all psychotherapy sessions recorded to audio/video.

        Exclusion Criteria:

          -  Are pregnant or nursing, or if they can have children and are not practicing 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.