Potential Psychiatric Uses for MDMA

This commentary (2016) highlights the psychiatric framework of MDMA-assisted psychotherapy, whereby the substance catalyzes the therapeutic treatment window, thus enabling processes such as psychoeducation, distress management, cognitive restructuring, emotion regulation, and interpersonal regulation to continue in the subsequent integration sessions. It also emphasizes the set and setting biological mechanisms underlying MDMA’s therapeutic action, and provides recommendations to boost the credibility of researching these outcomes and mechanisms for the purposes of gaining FDA-approval.

Abstract

“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.”

Authors: Berra Yazar-Klosinski & Michael C. Mithoefer

Summary

BACKGROUND

MDMA-assisted psychotherapy employs single doses of MDMA administered under continuous medical supervision on two to three occasions a month apart. The drug has been shown to have promising therapeutic applications, but remains in Schedule 1 by the Drug Enforcement Administration.

SET AND SETTING

MDMA-assisted psychotherapy has been studied in clinical trials treating PTSD, anxiety associated with life-threatening illness, and social anxiety in autistic adults. 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.

MECHANISM AND TARGET INDICATIONS

MDMA potentiates the release of monoamines and modulates the hypothalamic – pituitary – adrenal (HPA) axis, which may have important implications for PTSD treatment. MDMA also promotes neuroplasticity and regulates the HPA axis, improving functional outcomes through effects on learning and memory.

MDMA-assisted psychotherapy may improve self-knowledge, sleep regulation, accuracy in perceiving mental states of others, coping strategies, emotion regulation, and cognitive insights, and may be useful in the treatment of disorders associated with attachment insecurities, including PTSD, depression, anxiety disorders, obsessive-compulsive disorder, suicidality, substance use disorders, and eating disorders.

MDMA use is context-dependent and self-limiting, with moderate abuse potential. Studies suggest self-medication or intentional self-exploration as probable motivations for use, and an upcoming study of MDMA-assisted psychotherapy is planned for treatment of alcoholism.

REGULATORY PATHWAY AND MEDICAL NEED

Multiple phase II studies of MDMA-assisted psychotherapy for PTSD have shown promising results, and permission has been requested for a phase III program. The proposed phase III success criteria include statistical superiority over psychotherapy with placebo in reducing PTSD symptoms.

MDMA is administered as two to three single-dose treatments, frequently with a strong response after the first session. Single-dose toxicity studies are more appropriate than repeated-dose toxicology studies, and pre-postnatal development studies may be beyond the scope of what should be required.

The FDA has provided special programs with accelerated pathways for approval of MDMA for the treatment of PTSD, and will allow sponsor oversight of certification of treatment providers to assure that they have the necessary experience and qualifications to administer MDMA-assisted psychotherapy.

MDMA is not patentable and will be difficult to commercialize with single-dose treatments. A nonprofit organization is funding and sponsoring clinical trials of MDMA-assisted psychotherapy, which could offer improved safety and compliance over available treatments.

PDF of Potential Psychiatric Uses for MDMA