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MDMA and MDMA-Assisted Therapy
Aaron S Wolfgang1, Gregory A Fonzo1, Joshua C Gray1
1Directorate of Behavioral Health, Walter Reed National Military Medical Center, Bethesda, MD (Wolfgang); Departments of Psychiatry (Wolfgang) and Medical and Clinical Psychology (Gray), Uniformed Services University, Bethesda, MD; Departments of Psychiatry (Wolfgang, Krystal), Neuroscience (Krystal), and Psychology (Krystal), Yale University School of Medicine, New Haven, CT; Center for Psychedelic Research and Therapy, Department of Psychiatry and Behavioral Sciences, The University of Texas at Austin Dell Medical School (Fonzo, Nemeroff); Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, UCLA (Grzenda); Department of Psychiatry & Behavioral Sciences, University of Minnesota, Minneapolis (Widge); Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham (Kraguljac); Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (McDonald); Department of Psychiatry and Behavioral Sciences, Stanford University and Veterans Affairs Palo Alto Health Care System, Palo Alto, CA (Rodriguez).
MDMA-Assisted Therapy (MDMA-AT) shows promise for treating posttraumatic stress disorder (PTSD). Clinical trials indicate MDMA-AT is safe and effective, with significant symptom reduction compared to placebo.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- MDMA (3,4-methylenedioxymethamphetamine) has historical use in recreational and therapeutic contexts.
- The FDA designated MDMA-Assisted Therapy (MDMA-AT) as a Breakthrough Therapy for PTSD in 2017.
- Recreational MDMA use carries risks due to adulterants and lack of clinical oversight, limiting extrapolation to therapeutic settings.
Purpose of the Study:
- To differentiate evidence from recreational MDMA use versus controlled MDMA-AT.
- To review the neurobiological mechanisms underlying MDMA's therapeutic effects.
- To present clinical evidence, public health considerations, and future research directions for MDMA-AT.
Main Methods:
- Review of existing literature on MDMA use in clinical and nonclinical settings.
- Analysis of clinical trial data for MDMA-Assisted Therapy in PTSD.
- Examination of neurobiological and pharmacological data related to MDMA.
Main Results:
- MDMA uniquely promotes prosocial effects, trust, and self-compassion while preserving cognitive clarity.
- MDMA-AT in controlled settings demonstrates safety and efficacy for PTSD.
- Post-treatment, 67%-71% of individuals with PTSD no longer met diagnostic criteria after MDMA-AT, compared to 32%-48% with placebo.
Conclusions:
- MDMA-Assisted Therapy is a potentially groundbreaking treatment for PTSD, distinct from recreational use.
- Controlled clinical administration of pharmaceutical-grade MDMA with psychotherapy shows enduring positive outcomes.
- Further research and policy considerations are needed to optimize MDMA-AT's public health impact.
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