This Phase 2 pilot study examined the safety and efficacy of MDMA-assisted psychotherapy in 23 subjects with chronic, treatment-resistant PTSD.
The study assessed the change in symptoms of PTSD, as measured by the Clinical Administered PTSD Scale (CAPS) as well as symptoms of depression, as measured by the Beck Depression Inventory II (BDI-II) 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.
Country United States of America
Visit trial
Status
Completed
Results Published
Yes
Start date
01 October 2012
End date
01 February 2017
Chance of happening
100%
Phase
Phase II
Design
Blinded
Type
Interventional
Generation
First
Participants
29
Sex
All
Age
18- 99
Therapy
No
Trial Details
Posttraumatic stress disorder (PTSD) is a debilitating psychiatric disorder that can develop after a person experiences a traumatic event, such as sexual assault, war, or any other life-threatening event. PTSD is a worldwide health problem that severely reduces a person's quality of life and is associated with high rates of psychiatric and medical comorbidity, disability, suffering, and suicide. At least a third of PTSD patients fail to respond to established PTSD psychotherapies. A wider array of effective treatments for PTSD are needed. 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy may be a potential treatment option for PTSD. MDMA is a monoamine releaser that affects serotonin, norepinephrine, and dopamine. MDMA is capable of inducing unique psychopharmacological effects such as decreased feelings of fear, increased feelings of wellbeing, increased sociability and extroversion, increased interpersonal trust, and an alert state of consciousness. In the U.S., MDMA was used as an adjunct to psychotherapy by a considerable number of psychiatrists and therapists before it was placed in Schedule I in 1985 as a result of non-medical use. This Phase 2 pilot study is a randomized, double-blind, dose response study to examine the safety and efficacy of MDMA-assisted psychotherapy in 23 subjects with chronic, treatment-resistant PTSD of at least six months duration. This study is part of a global series of Phase 2 pilot clinical trials. This study assessed two active doses of MDMA, active dose 1 (100 mg) and active dose 2 (125 mg), to a comparator dose of MDMA (40 mg) during psychotherapy sessions. The initial dose of MDMA 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 orally in two experimental sessions lasting up to eight hours and scheduled three to five weeks apart. Subjects were prepared for MDMA-assisted psychotherapy in three preparatory sessions prior to the first experimental session, and worked with the same pair of therapists throughout the study. After each experimental session, three integrative sessions were scheduled with the subject, including one integrative session the morning after the experimental session. During integrative sessions, subjects processed and connected their thoughts and feelings about the experience with their therapist team. Subjects who received the comparator dose (40 mg) were given the option to enroll in Stage 2, where they underwent three open-label MDMA-assisted psychotherapy sessions. 100 mg of MDMA was administered in the first session and therapists determined whether to increase to 125 mg of MDMA for the second and third experimental sessions. People who received 125 mg of MDMA during the first two experimental sessions received the same dose during an open-label third experimental session. People who received 100 mg of MDMA during the first two sessions were able to choose, in consultation with their therapist, to either continue to receive 100 mg in a third session or to increase their dose to 125 mg. A blinded independent rater (IR) assessed the severity of PTSD symptoms at baseline, one month after the second experimental session (the primary endpoint), two months after the third open-label experimental session, and at equivalent points in Stage 2.NCT Number NCT01793610
Sponsors & Collaborators
MAPSMAPS stands for Multidisciplinary Association for Psychedelic Studies, it's the front runner in making psychedelics a legal way to use (and improve) in therapy.
Papers
Discontinuation of medications classified as reuptake inhibitors affects treatment response of MDMA-assisted psychotherapyA pooled analysis of participants (n=50) in Phase II MDMA trials for PTSD found that recent tapering off SSRIs may reduce treatment response (CAPS-IV score).
MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials
This pooled analysis (n=105; s=6) of MAPS' Phase II trials finds significant improvements (Cohen's d=0.8) and no significant adverse effects with MDMA-assisted therapy for PTSD. This analysis has been done to support starting the Phase III trials (which have taken place).
Long-term Follow-Up Outcomes of MDMA-assisted Psychotherapy for Treatment of PTSD: A Longitudinal Pooled Analysis of Six Phase 2 Trials
This long-term follow-up study (n=107) examines the effects of MDMA-assisted psychotherapy on PTSD symptoms. It finds a significant reduction in PTSD symptoms both at treatment exit and at least 12 months post-treatment, with 67% of participants no longer meeting PTSD criteria at long-term follow-up.
3,4-Methylenedioxymethamphetamine-assisted psychotherapy for treatment of chronic posttraumatic stress disorder: a randomized phase 2 controlled trial
This double-blind, between-subjects study (n=26) on the treatment of posttraumatic stress disorder (PTSD) compared the effectiveness of two higher (100-125mg) with one lower dose (40mg) of MDMA in combination with psychotherapy. One month after two sessions, the higher doses of MDMA showed the largest reduction on a PTSD Scale. At the 12-month follow-up, PTSD symptoms remained lower than baseline with 75% of the participants not meeting PTSD criteria.
Measures Used
Clinician-Administered PTSD Scale for DSM-5The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is often considered the gold standard in PTSD assessment. The 30-item structured interview was developed by staff at the U.S. Department of Veterans Affairs National Centre for PTSD. CAPS can be used to make a current diagnosis, lifetime diagnosis or assess PTSD symptoms over the past week in accordance with DSM-5 criteria.
Beck Depression Inventory
The Beck Depression Inventory (BDI) contains 21 self-report items, completed using a multiple-choice format. Scores range from 0-63 with higher scores associated with more severe depression.