Psychedelics and Psychiatry–the use of MDMA as a psychotherapy adjunct
Psychotherapy has been practiced in a form most similar to its modern manifestation since the 19th century when Sigmund Freud developed his psychoanalytic theory and its corresponding modality of therapy–psychoanalysis, later developed into psychotherapy. For many patients, therapy is invaluable, resulting in a reduced symptomatic response to illness; however, 40-60% of PTSD patients do not experience an apposite response to conventional therapy (qtd. in Feduccia and Mithoefer, 2018). That deviation represents a considerable public health risk, especially as the rates associated with PTSD-related suicides continue to climb. Additionally, the inability to successfully treat the patients has a direct impact on the state of healthcare and the furtherance of poor treatment. Beginning in 2010, there was a resurgence of psychedelic-assisted therapy research when a clinical study was published demonstrating that 83% of the experimental group no longer met the criteria for PTSD, and remission was maintained for a mean of 45 months after one 125 mg dose and one 62.5 mg dose of 3, 4-methylenedioxymethamphetamine ( MDMA) (Sessa et al., 2019). Then, in 2017, MDMA was deemed a breakthrough therapy for PTSD treatment, allowing the Multidisciplinary Association for Psychedelic Studies (MAPS) to sponsor phase three clinical trials studying MDMA-assisted psychotherapy. This retro approach to psychiatry may be here to stay: since 2010, there have been more studies supporting the hypotheses that postulate the valuable clinical applications of psychedelics in psychiatry, and there may be relief for innumerable people in these psychedelics.
The low response rate to typical psychotherapy in PTSD patients is not surprising. Many of the symptoms caused by the brain’s alteration of emotional processing and regulation have made it difficult for patients to remain in therapy due to their “emotional detachment, fragmentation of the trauma memories or an inability to complete the sessions due to inability to tolerate re-experiencing emotional content of the traumatic memory” (Feduccia and Mithoefer, 2018) as a result of the trauma exposure. However, in recent trials, it seems MDMA-assisted therapy may theoretically modify these responses by introducing fear extinction and allowing for the reconsolidation of these painful memories. This seems to be done through the influx of dopamine and serotonin released by the binding of the MDMA to certain receptors, acting as a high affinity agonist for the 5HT system (Sessa et al., 2019). Although the mechanism of action that MDMA has as a PTSD treatment is not well-known, it can be extrapolated that the flood of neurotransmitters associated with positive feelings and closeness, often producing euphoria and a “chatty” disposition, are responsible for the participants’ ability to successfully complete the trials as they include extensive therapy sessions and potential for multiple doses of MDMA, thereby potentially enhancing the therapeutic relationship and content of the session.
In a paper that addressed the phase two clinical trial of MDMA-assisted psychotherapy, the goal was “aimed at allowing participants to revisit traumatic experiences while staying emotionally engaged even during intense feelings of anxiety, pain, or grief without feeling overwhelmed. The relatively non-directive approach is intended to allow for processing of other psychological, interpersonal, or behavioral aspects of the participants’ lives that are likely to arise spontaneously in addition to processing the traumatic memories that led to PTSD” (Mithoefer et al., 2019). The MDMA-assisted approach, according to the trial, had a markedly higher efficacy than the control groups. Following a third round of “active dosing–”participants receiving a dose between 75mg and 125mg, followed by an eight-hour-long therapy session–the least squares mean change in the metric used to measure severity of PTSD symptoms reported by the participants was, on average, 35 points lower than those reported by the control group. Moreover, after all three rounds of treatment and therapy had been completed, 54.2% of participants in the experimental group no longer met the criteria for PTSD, compared to 22.6% of participants in the control group.
In the context of psychotherapy, MDMA is a psychedelic that has a considerable quantity of data supporting its efficacy in its role as an adjunct to therapy. With the completion of the second and final phase three clinical trial of MDMA-assisted psychotherapy for treatment of PTSD in 2022, and the data available from those trials–MAPP1 demonstrated that 88% of participants displayed significant improvements, 67% no longer met criteria for diagnosis, MAPP2 showed results from participants having moderate PTSD, not exclusively severe, and lastly, MAPP2 enrolled nearly twice as many participants of color–it is evident that there will be a New Drug Application in the near future (Kuntz, 2022). This presents a potentially very promising future for PTSD patients who have yet to find relief from their symptoms in psychotherapy or psychopharmacology.
References
Feduccia, A. A., & Mithoefer, M. C. (2018). MDMA-Assisted psychotherapy for PTSD: Are memory reconsolidation and fear extinction underlying mechanisms? Progress in Neuro-Psychopharmacology and Biological Psychiatry, 84, 221–228. https://doi.org/10.1016/j.pnpbp.2018.03.003
Kuntz, L. (2022, November 18). MDMA-Assisted therapy for PTSD: Completion of phase 3 study. Psychiatric Times. Retrieved February 2, 2023, from https://www.psychiatrictimes.com/view/mdma-assisted-therapy-for-ptsd-completion-of-phase-3-study
Mithoefer, M. C., Feduccia, A. A., Jerome, L., Mithoefer, A., Wagner, M., Walsh, Z., Hamilton, S., Yazar-Klosinski, B., Emerson, A., & Doblin, R. (2019). MDMA-Assisted psychotherapy for treatment of PTSD: Study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology, 236(9), 2735–2745. https://doi.org/10.1007/s00213-019-05249-5
Sessa, B., Higbed, L., & Nutt, D. (2019). A review of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy. Frontiers in Psychiatry, 10. https://doi.org/10.3389/fpsyt.2019.00138
U.S. Department of Health and Human Services. (2021, April 13). What is the history of MDMA? National Institutes of Health. Retrieved February 5, 2023, from https://nida.nih.gov/publications/research-reports/mdma-ecstasy-abuse/what-is-the-history-of-mdma
