Leslie A Morland, Chandra E Khalifian, Dimitri Perivoliotis, Bettye Chargin, Al Alam, Tamara R Wachsman, Dhakshin Ramanathan, Andrew W Bismark, Christopher Stauffer, Anne C Wagner, Abigail C Angkaw, Kayla C Knopp
Posttraumatic stress disorder (PTSD) disrupts individual well-being and relationship health, particularly among veteran/military couples with heightened risks due to deployment, family reintegration, and traumatic stress. Although cognitive-behavioral conjoint therapy (CBCT) and brief CBCT (bCBCT) have demonstrated strong efficacy in reducing PTSD symptoms, their impact on relational outcomes is less compelling. Given the importance of relationship functioning for veterans' overall health, enhancing interpersonal outcomes of PTSD treatment remains a research priority. One promising approach is the integration of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy to augment the relational benefits of established PTSD interventions. This single-site, open-label pilot study evaluated the preliminary benefit, safety, and acceptability of MDMA-assisted bCBCT in eight U.S. military veterans with PTSD and their intimate partners (N = 16). An eight-session MDMA-assisted bCBCT protocol with two MDMA administration sessions and dyadic integration sessions incorporating elements of integrative behavioral couples therapy was delivered. Outcomes included PTSD symptom severity, relationship functioning, and safety. Veterans exhibited large pre-post PTSD symptom reductions, d = 1.25, which were generally maintained during follow-up. Both veterans and partners experienced large improvements in relationship functioning, ds = 1.83 and 1.29, respectively, with moderate rebound during follow-up. No serious adverse events were reported. This first trial of MDMA-assisted bCBCT in U.S. veterans and their partners provides preliminary evidence of potential improvements in PTSD and relational outcomes, with no identified serious safety concerns. This model has potential for future evaluation in large health care systems, leveraging the hypothesized therapeutic effects of MDMA for individuals with PTSD and their families.