Indications
As previously noted, MDMA has been approved for clinical trials in the United States to treat PTSD, however MDMA is also being studied for its effectiveness treating other conditions.
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Alcohol Use Disorder
Preliminary research supports the safety of using MDMA-assisted therapy for treating alcohol use disorder. There was a study of 14 individuals who saw a drastic reduction in the average number of alcohol units consumed per week. These positive results continued even 9 months after treatment (Sessa et al., 2021).
Key Studies
Chronic Pain
Exploratory data analysis for participants with PTSD suggests that MDMA-assisted therapy may be beneficial in treating chronic pain. Among 32 individuals treated with MDMA-assisted therapy for severe treatment-resistant PTSD, there was a decrease in chronic pain and chronic-pain related disability among those with the highest pain score as measured by the CPGS (Christie et al., 2022).
Key Studies
“These findings demonstrate a high prevalence of pain in this sample of participants with severe PTSD, and that pain intensity, disability, and a composite pain severity index grade among those with the highest pain were significantly lower following MDMA-[assisted therapy].”
— Dr. Devon Christie et al. (2022).
Couples Therapy
While clinical studies on MDMA-assisted therapy have primarily focused on individuals, Wagner (2021) explores how couples therapy could be conducted with MDMA.
Key Studies
Learn More
To learn more about this area of research, please watch MDMA and Couples with Dr. Ann Wagner.
Eating Disorders
Exploratory data analysis for participants with PTSD suggests that MDMA-assisted therapy may be beneficial in treating eating disorder symptoms. Among 89 individuals with PTSD, a significant reduction in eating disorder scores was observed in comparison to the placebo group, after an intervention involving MDMA-assisted therapy to treat PTSD (Brewerton et al., 2022).
Key Studies
End-of-Life-Anxiety and Psychological Distress
In a study involving 18 individuals with anxiety or distress related to terminal illness, MDMA-assisted therapy produced a reduction in objective symptom measures, but it was not significantly greater than placebo in its effect (Wolfson et al., 2020). Further studies are needed.
Key Studies
Mood Disorders
Patel and Titheradge (2015) conducted a literature review of the studies that looked at MDMA as a rapid-onset antidepressant. As we will learn, depressed mood is a common reported side effect of MDMA consumption after the MDMA effects have finished, especially when consumed in a recreational setting. The results appear to be mixed: one study (Davison & Parrott, 1997) found 55% of participants experienced a depressed mood the following day while another found only 4% (De Almeida and Silva, 2003). One study (De Win et al., 2006) concluded that MDMA does not increase depression long-term while other studies (Lieb et al. 2002; Huizink et al. 2006; Briere et al. 2012) had contrary conclusions. In another study, Majumder et al. (2012) concluded that a decrease in depressive symptoms was observed in participants who consumed MDMA.
Key Studies
Post-Traumatic Stress
MDMA-assisted therapy has been shown to be able to be carried out safely in those with chronic PTSD who had not had success with previous treatments (Mitchell et all 2021; Bouso et al., 2008; Mithoefer et al., 2013). Additionally, MDMA-assisted therapy has been shown in several published randomized controlled trials to provide significant improvement in patients with moderate to severe PTSD (Jerome et al., 2020; Mithoefer et al., 2019; Mithoefer et al., 2011; Oehen et al., 2013). A Phase 3 randomized, double-blind, placebo-controlled trial of MDMA-assisted therapy with 90 participants suffering from moderate to severe PTSD and a range of common comorbidities demonstrated significant improvement in PTSD as measured by the CAPS-5 compared with the placebo (Mitchell et al., 2021). Long-term follow-up indicated that 67% of participants no longer met diagnostic criteria for PTSD and participants improved after 1 year without any further intervention (Mitchell et al., 2022). A longitudinal pooled analysis of six Phase 2 trials displayed that PTSD symptoms were reduced 1-2 months after MDMA-assisted therapy with symptoms continuing to improve at least 12 months after the treatment which supported the expansion into Phase 3 trials and led to the FDA granting Breakthrough Therapy designation to this treatment method (Jerome et al., 2020; Mithoefer et al., 2019). Some research has been conducted specifically examining certain populations, such as service-related PTSD in first responders and veterans where similar positive outcomes have been observed (Mithoefer et al., 2018). As of 2019, MAPS had completed 11 blinded, randomized, controlled Phase 2 and Phase 3 studies of MDMA-assisted therapy for PTSD, although most published data stems from Phase 2 trials (MAPS, 2021; Mithoefer et al., 2019).
Key Studies
“The reality is that we don’t presently have great treatments for PTSD. If the initial phase 3 trial results are confirmed, there is little doubt that MDMA assisted psychotherapy may represent an important new tool that can potentially provide relief to many who are suffering.”
— Dr. Evan Wood, Numinus Therapist (2022, personal communication).
Activity
Select one of the key studies above. Read through the study and summarize the main points in this document. The password for the document is mdma.
References
Bouso, J. C., Doblin, R., Farré, M., Alcázar, M. A., & Gómez-Jarabo, G. (2008). MDMA-assisted psychotherapy using low doses in a small sample of women with chronic posttraumatic stress disorder. J Psychoactive Drugs, 40(3), 225-236. https://doi.org/10.1080/02791072.2008.10400637
Brewerton, T. D., Lafrance, A., & Mithoefer, M. C. (2021). The potential use of N-methyl-3,4-methylenedioxyamphetamine (MDMA) assisted psychotherapy in the treatment of eating disorders comorbid with PTSD. Med Hypotheses, 146, 110367. https://doi.org/10.1016/j.mehy.2020.110367
Briere, J. (2012). Working with trauma: Mindfulness and compassion. Compassion and wisdom in psychotherapy (C. K. Germer and R. D. Seigel, Eds.), 265-79. Guilford. https://www.researchgate.net/publication/270647729_Working_with_trauma_Mindfulness_and_compassion
Christie, D., Yazar-Klosinski, B., Nosova, E., Kryskow, P., Siu, W., Lessor, D., & Argento, E. (2022). MDMA-assisted therapy is associated with a reduction in chronic pain among people with post-traumatic stress disorder. Frontiers in Psychiatry, 13, https://www.frontiersin.org/articles/10.3389/fpsyt.2022.939302/full
Danforth, A. L., Grob, C. S., Struble, C., Feduccia, A. A., Walker, N., Jerome, L., . . . Emerson, A. (2018). Reduction in social anxiety after MDMA-assisted psychotherapy with autistic adults: a randomized, double-blind, placebo-controlled pilot study. Psychopharmacology (Berl), 235(11), 3137-3148. https://doi.org/10.1007/s00213-018-5010-9
Davison, D. & Parrott, A. C. (1997). Ecstasy (MDMA) in Recreational Users: Self-Reported Psychological and Physiological Effects. Human Psychopharmacology, 12, 221-226. https://psy.swansea.ac.uk/staff/parrott/p-and-davisonHP-97.pdf
de Win, M. M., Schilt, T, Reneman L, Vervaeke H, Jager G, Dijkink S, Booij J, van den Brink W (2006) Ecstasy use and self-reported depression, impulsivity, and sensation seeking: a prospective cohort study. J Psychopharmacol 20:226–235
Feduccia, A. A., Holland, J., & Mithoefer, M. C. (2018). Progress and promise for the MDMA drug development program. Psychopharmacology (Berl), 235(2), 561-571. https://doi.org/10.1007/s00213-017-4779-2
Feduccia, A. A., Jerome, L., Yazar-Klosinski, B., Emerson, A., Mithoefer, M. C., & Doblin, R. (2019). Breakthrough for Trauma Treatment: Safety and Efficacy of MDMA-Assisted Psychotherapy Compared to Paroxetine and Sertraline. Front Psychiatry, 10, 650. https://doi.org/10.3389/fpsyt.2019.00650
Huizink, A. C., Ferdinand, R. F., van der Ende, J., & Verhulst, F. C. (2006). Symptoms of anxiety and depression in childhood and use of MDMA: prospective, population based study. BMJ (Clinical research ed.), 332(7545), 825–828. https://doi.org/10.1136/bmj.38743.539398.3A
Jerome, L., Feduccia, A. A., Wang, J. B., Hamilton, S., Yazar-Klosinski, B., Emerson, A., . . . Doblin, R. (2020). Long-term follow-up outcomes of MDMA-assisted psychotherapy for treatment of PTSD: a longitudinal pooled analysis of six phase 2 trials. Psychopharmacology (Berl), 237(8), 2485- 2497. https://doi.org/10.1007/s00213-020-05548-2
Lieb, R., Isensee, B., Höfler, M., Pfister, H., & Wittchen, H.-U. (2002). Parental major depression and the risk of depression and other mental disorders in offspring: a prospective-longitudinal community study. Archives of general psychiatry, 59(4), 365–374. https://doi.org/10.1001/archpsyc.59.4.365
Majumder, I., White J. M., Irvine, R. J. (2012). Antidepressant-like effects of ecstasy in subjects with a predisposition to depression. Addictive Behaviour, 37(10), 1189-92. doi: 10.1016/j.addbeh.2012.05.022.
Mitchell JM, Bogenschutz M, Lilienstein A, Harrison C, Kleiman S, Parker-Guilbert K, Ot'alora G M, Garas W, Paleos C, Gorman I, Nicholas C, Mithoefer M, Carlin S, Poulter B, Mithoefer A, Quevedo S, Wells G, Klaire SS, van der Kolk B, Tzarfaty K, Amiaz R, Worthy R, Shannon S, Woolley JD, Marta C, Gelfand Y, Hapke E, Amar S, Wallach Y, Brown R, Hamilton S, Wang JB, Coker A, Matthews R, de Boer A, Yazar-Klosinski B, Emerson A, Doblin R (2021). MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med, 27(6), 1025-1033. https://doi.org/10.1038/s41591-021-01336-3
Mithoefer, M. C., Feduccia, A. A., Jerome, L., Mithoefer, A., Wagner, M., Walsh, Z., . . . 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 (Berl), 236(9), 2735-2745. https://doi.org/10.1007/s00213-019-05249-5
Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T., Jerome, L., Martin, S. F., Yazar-Klosinski, B., . . . Doblin, R. (2013). Durability of improvement in post-traumatic stress disorder symptoms and absence of harmful effects or drug dependency after 3,4-methylenedioxymethamphetamine- assisted psychotherapy: a prospective long-term follow-up study. J Psychopharmacol, 27(1), 28- 39. https://doi.org/10.1177/0269881112456611
Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T., Jerome, L., & Doblin, R. (2011). The safety and efficacy of {+/-}3,4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress disorder: the first randomized controlled pilot study. J Psychopharmacol, 25(4), 439-452. https://doi.org/10.1177/0269881110378371
Oehen, P., Traber, R., Widmer, V., & Schnyder, U. (2013). A randomized, controlled pilot study of MDMA (± 3,4-Methylenedioxymethamphetamine)-assisted psychotherapy for treatment of resistant, chronic Post-Traumatic Stress Disorder (PTSD). J Psychopharmacol, 27(1), 40-52. https://doi.org/10.1177/0269881112464827
Patel, R., & Titheradge, D. (2015). MDMA for the treatment of mood disorder: all talk no substance?. Therapeutic advances in psychopharmacology, 5(3), 179–188. https://doi.org/10.1177/2045125315583786
Pereira De Almeida, S. & Araujo Silva, M. T. (2003). Ecstasy (MDMA): Effects and patterns of use reported by users in São Paulo. Revista Brasileira de Psiquiatria, 25(1), 11-7. https://www.scielo.br/j/rbp/a/jZfq4vwqNzKVqTzFjZsV4WQ/?format=pdf&lang=en
Riedlinger J, Montagne M. Using MDMA in the treatment of depression. In: Holland J, editor. Ecstasy: The Complete Guide: A Comprehensive Review of the Risks and Benefits of MDMA. Inner Traditions; (2001). p. 261–73.
Sessa, B., Sakal, C., O'Brien, S., & Nutt, D. (2019). First study of safety and tolerability of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in patients with alcohol use disorder: preliminary data on the first four participants. BMJ Case Rep, 12(7). https://doi.org/10.1177/0269881121991792
Wagner, A. C. (2021). Couple Therapy With MDMA—Proposed Pathways of Action. Frontiers in Psychology, 12, https://doi.org/10.3389/fpsyg.2021.733456
Wolfson, P. E., Andries, J., Feduccia, A. A., Jerome, L., Wang, J. B., Williams, E., . . . Doblin, R. (2020). MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study. Sci Rep, 10(1), 20442. https://doi.org/10.1038/s41598-020-75706-1
Yazar-Klosinski, B. and Mithoefer, M. (2017), Potential Psychiatric Uses for MDMA. Clin. Pharmacol. Ther., 101: 194-196. https://doi.org/10.1002/cpt.565
Social Anxiety Among Adults with Autism
MDMA-assisted therapy has shown benefit for improving social anxiety symptoms in adults with autism. This study involved 12 participants receiving either MDMA or a placebo as part of a therapy program with outcomes measured 6 months after the end of treatment showing positive results (Danforth et al., 2018).
Key Studies