Prevalence of Potential Contraindications and Risk Factors Relevant to MDMA-Assisted Therapy Among U.S. Veterans with Posttraumatic Stress Disorder

3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy has emerged as a potential strategy to treat posttraumatic stress disorder (PTSD). We conducted a national serial cross-sectional study of U.S. Veterans with PTSD from January 1, 2018, to December 31, 2023, to quantify the prevalence of potential contraindications, risk factors, and drug-drug interactions relevant to MDMA-assisted therapy. Participants were required to have at least two diagnostic codes for PTSD within a calendar year. Each year, 303,451 to 326,315 participants received care for PTSD. The annual proportion of individuals with at least one contraindication for MDMA-assisted therapy ranged from 15.3% to 17.3%, and the annual proportion with at least one conditional or modifiable risk factor ranged from 55.2% to 58.2%. Each year, 85.7% to 87.5% of participants filled at least one prescription for another medication that potentially interacts with MDMA. Many individuals with PTSD have contraindications or conditional risk factors that may require additional evaluation prior to receiving MDMA-assisted therapy, but many may be eligible with careful management of modifiable conditions and potential drug-drug interactions. Our results have important implications for policymakers and clinicians as studies examining the safety and efficacy of MDMA-assisted therapy continue to evolve toward potential implementation.