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Symposia

Treatment - CBT

Expanding the Frontiers of CBT: Emerging Evidence and Equitable Engagement in Psychedelic- and MDMA-Assisted Therapies

2 - (SYM 23) The Promise of MDMA in Combination with Prolonged Exposure Therapy for Posttraumatic Stress Disorder

Friday, November 21, 2025
5:22 PM - 5:39 PM CST
Location: Empire D, Level 2
Keywords: Randomized Controlled Trial, CBT, Psychotherapy Outcome
Recommended Readings: Luoma, J. B., Sabucedo, P., Eriksson, J., Gates, N., & Pilecki, B. C. (2019). Toward a contextual psychedelic-assisted therapy: perspectives from acceptance and commitment therapy and contextual behavioral science. Journal of Contextual Behavioral Science, 14, 136-145.,   Weintraub, M. J., Jeffrey, J. K., Grob, C. S., Ichinose, M. C., Bergman, R. L., Cooper, Z. D., & Miklowitz, D. J. (2023). Psilocybin-Assisted Cognitive Behavioral Therapy for Adults with Major Depressive Disorder: Rationale and Treatment Development. Psychedelic Medicine, 1(4), 230-240.,   Morland, L. A., Perivoliotis, D., Wachsman, T. R., Alam, A., Knopp, K., Khalifian, C., ... & Wagner, A. C. (2024). MDMA-assisted brief cognitive behavioral conjoint therapy for PTSD: Study protocol for a pilot study. Contemporary Clinical Trials Communications, 40, 101314.,   Rothbaum, B. O., & Maples-Keller, J. L. (2023). The promise of 3, 4-methylenedioxymethamphetamine (MDMA) in combination with prolonged exposure therapy for posttraumatic stress disorder. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 48(1), 255-256.,   Lear, M. K., Smith, S. M., Pilecki, B., Stauffer, C. S., & Luoma, J. B. (2023). Social anxiety and MDMA-assisted therapy investigation: A novel clinical trial protocol. Frontiers in Psychiatry, 14, 1083354.
Abstract Body

Background. In a phase 3 trial, 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy, a non-directive therapeutic approach, resulted in significantly greater reductions in PTSD compared to placebo. The only interventions recommended as first-line treatments are trauma-focused psychotherapies: Prolonged Exposure (PE), Cognitive Processing Therapy, Eye Movement Desensitization and Reprocessing. PTSD can be understood using a translational fear extinction model in which exposure to a trauma represents an unconditioned stimulus (US) that elicits an unconditioned fear response. Translational research supports that MDMA facilitates the extinction of fear. In rodent models, MDMA enhances the extinction of both conditioned freezing and fear-potentiated startle, which is highly conserved across species. In a randomized, placebo-controlled trial with healthy adults using the same experimental startle paradigm, significantly more participants in the MDMA group retained extinction learning compared to the placebo group (χ2=7.29, p = 0.007). Methods. We have developed The METEMP Protocol for Massed Exposure Therapy Enhanced with MDMA for PTSD. This combined protocol and preliminary data will be presented. Results. Current results indicate significant PTSD symptom reduction with an average decrease in the CAPS-5-R of 65.07 (average CAPS-R of 73.75 [SD 11.23] and 8.68 [SD 9.24] at pre-treatment and 1-month post-treatment follow-up, respectively) and average decrease in PCL-5 of 33.13 (average PCL-5 of 45.13 [SD 8.43] and 13.57 [SD 15.23] at pre- treatment and 1-month post-treatment follow-up, respectively). Conclusions. Translational evidence indicates PE could represent the optimal psychotherapy to be combined with MDMA for PTSD intervention.