Potential Psychiatric Uses for MDMA

B.B. Yazar-Klosinski and M.C. Mithoefer

CLINICAL PHARMACOLOGY & THERAPEUTICS, 2017, 101, 2

www.wileyonlinelibrary/cpt

doi:10.1002/cpt.565

 

Phase II trials of 3,4-methylenedioxymethamphetamine (MDMA)- assisted psychotherapy have demonstrated initial safety and efficacy for treatment of posttraumatic stress disorder (PTSD), with potential for expansion to depression and anxiety disorders. In these trials, single doses of MDMA are administered in a model of medication-assisted psychotherapy, differing from trials involving daily drug administration without psychotherapy. This model presents an opportunity to utilize accelerated regulatory pathways, such as the US Food and Drug Administration (FDA) Breakthrough Therapy Designation, to most effectively and expeditiously test such novel approaches.

BACKGROUND

MDMA-assisted psychotherapy employs single doses, administered under continuous medical supervision on two to three occasions a month apart. Drug administration is preceded by preparatory sessions and followed by psychotherapy sessions supporting integration of therapeutic changes into daily life (Figure 1). MDMA was placed in Schedule 1 by the Drug Enforcement Administration (DEA) in 1985 on the basis of widespread nonmedical use and concerns of abuse potential, despite a Schedule 3 recommendation by an administrative law judge. The results indicate promising therapeutic applications, but MDMA remains in Schedule 1, defined as having no accepted medical use, high abuse potential, and lack of accepted safety. Data from phase II randomized controlled trials (RCTs) exploring MDMA-assisted psychotherapy were submitted to the FDA as initial indications of safety and efficacy. These studies build on published case reports on clinical use of MDMA prior to DEA scheduling.1 Completion of successful phase III trials is the remaining requirement for FDA approval of MDMA as a therapeutic agent.

SET AND SETTING

An array of chronic psychiatric disorders share a common core of intractable symptoms that respond favorably to MDMA-assisted psychotherapy, which has been studied in clinical trials treating PTSD, anxiety associated with life-threatening illness, and social anxiety in autistic adults.2 These studies demonstrate the success of careful approaches to therapeutic set and setting designed to minimize adverse events and maximize benefits with minimal targeted exposure to drug. All recent MDMA-assisted psychotherapy registration studies are RCTs, meeting rigorous standards for drug development regulated by the FDA and overseen by Institutional Review Boards (IRBs). Furthermore, due to the Schedule 1 status of MDMA, compliance with DEA and statelevel controlled substance review committees is required, placing these studies in the most regulated area of drug development, and introducing a disincentive to potential researchers. Researchers who are willing to take on the challenge of managing compliance with this complex oversight often only do so because of the potential to relieve suffering that has not responded to existing established treatments, and the hope of providing the field of psychiatry with methods of effectively combining psychopharmacology with psychotherapy in a patient-centered approach that respects and fosters the innate healing capacity of the individual.

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