The authors of an editorial in the October JAMA Psychiatry journal emphasize that the psychotherapy component is a critical factor in assessing the efficacy of MDMA-assisted therapy.
An editorial in the October JAMA Psychiatry journal emphasizes that psychotherapy is a critical factor in assessing the efficacy of MDMA-assisted therapy for treating post-traumatic stress disorder, and urges further study of psychotherapy’s role in the treatment model.
In their October 2024 viewpoint in JAMA Psychiatry, Ioana Alina Cristea, Pim Cuijpers and Joar Øveraas Halvorsen highlight concerns about the lack of standardization and empirical support for the specific therapeutic approach used in the trials conducted by Lykos Theraputics. On Aug. 9, the U.S. Food & Drug Administration rejected the company’s new-drug application for MDMA-assisted therapy in the treatment of PTSD.
Designed by the Lykos – formerly the Multidisciplinary Association for Psychedelic Studies (MAPS) – the therapeutic trials included preparatory, active and integrative phases, with both drug and placebo groups receiving the same sequence, albeit under MDMA’s influence in the treatment group.
Cristea, Cuijpers and Halvorsen point out that the FDA previously has approved drugs that are part of a treatment plan that includes counseling or psychosocial support. However, the Lykos application marked the first time the agency had to evaluate a drug “that is assumed to work only accompanied by a specific psychotherapy.”
“The psychotherapy accompanying MDMA is not standard of care and has not been studied previously for PTSD or any other mental disorder,” the authors assert. “In previous studies of pharmacological or psychological enhancement of a psychiatric treatment, the intervention to be enhanced had established efficacy, such as D-cycloserine augmentation for exposure-based therapy or a novel cognitive task to extend the effects of a single infusion of ketamine. Conversely, MDMA-assisted psychotherapy is a combination of two experimental elements, each of unknown efficacy or safety.”
The authors add that the Lykos NDA was “singular because the FDA does not regulate psychotherapy.”
Cristea, Cuijpers and Halvorsen express concern over the variability and subjectivity allowed within the therapy sessions, which follow a nondirective manual that gives therapists significant discretion over therapeutic elements, including exposure techniques and cognitive restructuring. Such variability could have led to inconsistent treatment delivery across groups, potentially skewing outcomes, they assert.
Another concern is that the manual includes alternative, esoteric techniques lacking empirical support, such as somatic experiencing, holotropic breathwork and concepts such as “inner healing intelligence.”
“These concepts lack empirical evidence and are not even operationalized to allow measuring,” the authors assert. “They are not derived from any tested or testable theory and are not recommended by clinical practice guidelines.”
Established evidence-based PTSD therapies such as prolonged exposure (PE) and cognitive processing therapy (CPT) are founded on well-researched theoretical models, they add, while MDMA-assisted psychotherapy relies on untested, abstract concepts, making it difficult to measure and compare efficacy.
Ultimately, Cristea and colleagues suggest that the MDMA-therapy combination warrants further examination to identify its active components, potential standalone effects and susceptibility to bias from therapy variability. A more standardized, evidence-based approach, perhaps using established therapies such as PE or CPT, could strengthen the reliability of future studies. Additionally, testing MDMA’s effects with simpler therapeutic elements in controlled, subclinical environments could help refine its application and assess whether MDMA truly enhances psychotherapeutic outcomes for PTSD.