The Psychotherapy in MDMA-Assisted Psychotherapy

Ioana Alina Cristea; Pim Cuijpers; Joar 脴veraas Halvorsen

doi:10.1001/jamapsychiatry.2024.2887

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Viewpoint

October 2, 2024

The Psychotherapy in MDMA-Assisted Psychotherapy

Ioana Alina聽Cristea,聽PhD¹; 笔颈尘听颁耻颈箩辫别谤蝉,听笔丑顿²; Joar 脴veraas聽Halvorsen,聽PhD^3,4

Author Affiliations Article Information

¹Department of General Psychology, University of Padova, Padova, Italy
²Department of Clinical, Neuro and Developmental Psychology, WHO Collaborating Centre for Research and Dissemination of Psychological Interventions, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
³Psychological Outpatient Clinic for Adults, Department of Psychology, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
⁴St Olav鈥檚 University Hospital, Trondheim, Norway

JAMA Psychiatry. 2024;81(11):1053-1054. doi:10.1001/jamapsychiatry.2024.2887

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On June 4, 2024, the Psychopharmacologic Drugs Advisory Committee for the Food and Drug Administration (FDA) overwhelmingly voted that the efficacy of midomafetamine/3,4-methylenedioxymethamphetamine (MDMA)鈥揳ssisted psychotherapy for posttraumatic stress disorder (PTSD) was yet unsupported and that safety risks outweighed the treatment benefits. On August 9, 2024, the FDA followed the recommendation of the Advisory Committee and declined to approve MDMA-assisted psychotherapy. The intervention is composite, and its outcomes assumed to result from MDMA facilitating the effects of psychotherapy.¹^,2 In this Viewpoint, we argue that the psychotherapy component plays a critical role in assessing the validity of the trials.

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November 5, 2024

Clarifying Misconceptions About MDMA-Assisted Psychotherapy

Michael Alpert, M.D. | Department of Psychiatry, Beth Israel-Deaconess Medical Center - Harvard Medical School

The authors of 鈥淭he Psychotherapy in MDMA-Assisted Psychotherapy鈥� (Cristea IA, 2024) demonstrate a superficial understanding of the therapeutic model that they attempt to critique. The concept of an 鈥渋nner healing intelligence鈥� is a transtheoretical construct that asserts the innate capacity for each person to engage in self-directed healing and growth. It contrasts with more deterministic models of the mind, in which patients are passive bystanders to unconscious drives or the neurobiological effects of pharmacological interventions. A forthcoming paper on the theoretical lineages of the MDMA-Assisted Therapy model elaborates further on this topic (O鈥橠onnell KC, 2024). Initial inquiries into the concept of inner healing intelligence and its association with clinical outcomes have shown promising results (Peill J, 2024).

The authors appear unaware of how this model was implemented, a process that is summarized in the supplementary appendix accompanying the published results from a multisite trial of MDMA-Assisted Therapy (Mitchell JM, 2023). In brief, in addition to completing online modules and an in-person workshop, study therapists were monitored through video review by both supervisors and independent observers (i.e., Adherence Raters, AR). For AR review, the Therapy Manual was operationalized into a separate Adherence Manual: a set of core competencies and requirements specific to each phase of treatment. Treatment outcomes did not vary significantly across study sites (Mitchell JM, 2023), suggesting that the training and supervision process was sufficient to ensure fidelity.

The authors have also overlooked the success of the 鈥減sychotherapy only鈥� arms of these trials (Mitchell JM, 2023). Said success is even more remarkable if participants in these placebo arms were indeed subject to negative expectancy bias. In another measure of successful treatment, the dropout rates from the placebo arms were roughly one third the dropout rates seen in meta-analyses of Cognitive Processing Therapy (CPT) and Prolonged Exposure (PE) (McLean CP, 2022), with an effect size comparable to both modalities.

Taking these findings into account, a different perspective on this treatment emerges that can help guide future directions for research. While we can and should investigate the use of other models of psychotherapy in conjunction with MDMA, assuming a priori that such therapies should be used as standard of care in conjunction with MDMA ignores the growing evidence base for the MDMA psychotherapy model established in the Phase 3 trials, and does a disservice to those individuals living with PTSD who have been, or could be, helped by that model鈥攑articularly when existing treatments have failed them.

References
Cristea IA, Cuijpers P, Halvorsen J脴. The Psychotherapy in MDMA-Assisted Psychotherapy. JAMA Psychiatry. 2024 Oct 2. Epub ahead of print.

McLean CP, Levy HC, Miller ML, Tolin DF. Exposure therapy for PTSD: A meta-analysis. Clinical psychology review. 2022 Feb 1;91:102115.

Mitchell JM, et al. MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial. Nature Medicine. 2023 Oct;29(10):2473-80.

O'Donnell, Kelley C., et al. "The Conceptual Framework for the Therapeutic Approach Used in Phase 3 Trials of MDMA-Assisted Therapy for PTSD." Frontiers in Psychology 15: 1427531.

Peill, Joseph, et al. "Psychedelics and the 鈥榠nner healer鈥�: Myth or mechanism?." Journal of Psychopharmacology 38.5 (2024): 417-424.

CONFLICT OF INTEREST: Michael Alpert receives payments from Lykos Therapeutics, Inc. as an investigator to work on clinical trials and contracts with Lykos Therapeutics, Inc. to perform education and supervision services.

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