Psychedelic Therapy: A Primer for Primary Care Clinicians – Part VI. 3,4-methylenedioxy-methamphetamine (MDMA)

Background: After becoming notorious for its use as a party drug in the 1980s, 3,4-methylenedioxy-methampetamine (MDMA), also known by its street names “molly” and “ecstasy,” has emerged as a powerful treatment for post-traumatic stress disorder (PTSD). Areas of uncertainty: There is extensive data about the risk profile of MDMA. However, the literature is significantly biased. Animal models demonstrating neurotoxic or adverse effects used doses well beyond the range that would be expected in humans (up to 40 mg/kg in rats compared to roughly 1-2 mg/kg in humans). Furthermore, human samples are often comprised of recreational users who took other substances in addition to MDMA, in uncontrolled settings. Therapeutic advances: Phase III FDA clinical trials led by the Multidisciplinary Association for Psychedelic Studies (MAPS) have shown that MDMA-assisted psychotherapy has an effect size of d = 0.7-0.91, up to 2-3 times higher than the effect sizes of existing antidepressant treatments. 67 to 71% of patients who undergo MDMA-assisted psychotherapy no longer meet the diagnostic criteria for PTSD within 18 weeks. We also describe other promising applications of MDMA-assisted psychotherapy for treating alcohol use disorder, social anxiety, and other psychiatric conditions. Conclusions: While there have only been six clinical trials for PTSD thus far, all organized by MAPS, the preliminary evidence suggests that MDMA is much more effective than existing antidepressant medications for treating PTSD.