Rick Doblin, PhD, founder and executive director of the Multidisciplinary Association for Psychedelic Studies (MAPS), anticipates that 3,4-methylenedioxymethamphetamine (MDMA) will be approved for the treatment of posttraumatic stress disorder (PTSD) by 2021. During his presentation at the 2019 Psych Congress, held October 3 to 6 in San Diego, California, Dr Doblin discussed results of recent research and future directions for treatment of PTSD.1
Millions of Americans are affected by PTSD.2 Among veterans, it is the third most prevalent military service-related disability, which costs the Veterans Affairs disability payments service billions of dollars each year.3 Furthermore, treatment for PTSD can be challenging given the high number of nonresponders.
MDMA, a known psychoactive drug that is most often used recreationally, has been identified as potential therapeutic modality for this challenging condition. MDMA counters the neurologic effects of PTSD, which manifest as hypoactivity in both the hippocampus and prefrontal cortex and hyperactivity in the amygdala.
MDMA is not the entire therapy for PTSD; instead, it is MDMA-assisted psychotherapy — optimized with thorough preparation and integration of therapeutic outcomes — that has had early success in PTSD in multiple phase 2 trials and has now moved on to phase 3 studies.4
In a series of 6 international phase 2 MAPS-sponsored studies, an active dose of MDMA (75-125 mg) was compared with a nonactive lower dose (0-40 mg; placebo group) in MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD over multiple integrative sessions.4
At 2-month follow-up, more than half of patients who received the active MDMA dose no longer met the diagnostic criteria for PTSD (56% vs 23% in the placebo group). This improvement in PTSD with an active dose of MDMA was even greater at 12-month follow-up: two-thirds of patients (68%) were categorized as no longer having PTSD, indicating prolonged healing after MDMA-assisted therapy.4
On the day of administration, rates of anxiety, jaw clenching/tight jaw, lack of appetite, and nausea were higher in patients who received the active dose of MDMA, while fatigue and headache were more common in the comparator group. Despite concerns about longer-term neurotoxicity with MDMA, the investigators noted no neurocognitive changes after treatment.4
On the basis of these data, the United States Food and Drug Administration (FDA) approved the trial to move to phase 3 and granted breakthrough designation for MDMA-assisted psychotherapy for PTSD in 2017.5 The European Medicines Agency also approved the study to move to phase 3, with the condition that migrants and refugees be included. An interim analysis of the first of the phase 3 studies is expected around March 2020.
Though costs for MDMA drug development are high — an estimated $34 million before FDA approval and $11 million related to European Medicines Agency approval — MAPS, a nonprofit organization, is refusing investment from pharmaceutical companies in an effort to avoid competing interests. Representatives from MAPS are in conversations with the FDA to discuss expanded access through compassionate use, given that there are millions of patients with PTSD and only hundreds currently being enrolled in clinical trials.
As for next steps, Dr Doblin explained that patients with PTSD have a desperate need for this therapy. While MDMA-assisted treatment will never be a take-home, self-administered cure, he envisions a future with highly trained therapists at thousands of accessible psychedelic treatment centers across the world.
For more coverage of Psych Congress 2019, click here.
1. Doblin R. MDMA-assisted psychotherapy for PTSD: to phase 3 and beyond. Presented at: Psych Congress 2019; October 3-6, 2019; San Diego, CA.
2. PTSD: National Center for PTSD. US Department of Veterans Affairs website. https://www.ptsd.va.gov/understand/common/common_adults.asp. Accessed October 4, 2019.
3. Annual benefits report FY 2018, Compensation. US Department of Veterans Affairs website. https://benefits.va.gov/REPORTS/abr/docs/2018-compensation.pdf. Accessed October 4, 2019
4. Mithoefer MC, Feduccia AA, Jerome L, et al. 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. Psychopharmacol. 2019;236(9):2735-2745.
5. FDA grants breakthrough therapy designation for MDMA-assisted psychotherapy for PTSD, agrees on special protocol assessment for phase 3 trials [press release]. Santa Cruz, California; Multidisciplinary Association for Psychedelic Studies (MAPS); August 26, 2017.