Randomized, Double-blind, Placebo-Controlled Pilot Study of MDMA-assisted Therapy for PTSD

A Randomized, Double-Blind, Active Placebo-Controlled Phase 2 Pilot Study of MDMA-assisted Psychotherapy in People With Chronic, Treatment-Resistant Posttraumatic Stress Disorder (PTSD)

The goal of this clinical trial is to learn if MDMA-assisted therapy is safe and effective in people with chronic, treatment-resistant PTSD.

The main question it aims to answer is: Is there a reduction in PTSD symptoms in people given a low dose of MDMA with therapy versus a high dose of MDMA with therapy?

Researchers will compare two sessions of MDMA-assisted therapy with either 25 mg of MDMA HCl or 125 mg of MDMA HCl in Stage 1.

Participants will undergo preparatory therapy sessions without any study drug, followed by two sessions of MDMA-assisted therapy, each followed by integrative therapy sessions without study drug. Participants who received 25 mg during Stage 1 will be given the option to enroll in Stage 2 and complete two additional open-label MDMA-assisted therapy sessions with the full dose of 125 mg MDMA.

This randomized, double-blind, active placebo-controlled Phase 2 pilot study investigated 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 midomafetamine HCl, followed by a supplemental half-dose of 62.5 mg after 1.5 to 2.5 hours. The remaining eight subjects enrolled in Stage 1 of the study and received either an active placebo dose (low dose of 25 mg midomafetamine HCl with a supplemental half-dose of 12.5 mg) or a fully active dose (125 mg midomafetamine HCl with a supplemental half-dose of 62.5 mg) during two experimental psychotherapy session, each lasting six to eight hours and scheduled three to five weeks apart.

Upon enrollment, subjects met with their therapist team for three preparatory sessions. After each MDMA-assisted psychotherapy session, subjects met with their therapist team for integrative psychotherapy sessions.

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). Safety measures, vital signs, and a measurement of psychological distress was assessed during all experimental sessions. Blood pressure and heart rate were assessed periodically during each experimental session.

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 midomafetamine HCl (125 mg and 62.5 mg supplemental) on the same schedule as Stage 1.

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.
• Have used "Ecstasy" (material represented as containing MDMA) more than five times or at least once within 6 months of the MDMA session.
• 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.