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Recent advances in sleep research have shown that overall sleep quality is associated with a person’s physical and mental wellbeing (Tahmasian et al., 2020). As such, sleep disturbances are a common feature of many mental disorders, including posttraumatic stress disorder (PTSD), in which people often suffer from recurrent nightmares and insomnia (Krystal, 2013). 
PTSD is a debilitating mental health condition triggered by experiencing or witnessing a traumatic event. Symptoms of PTSD are usually categorized into four types: intrusive memories, avoidance, negative changes in thinking and mood, and changes in physical and emotional reactions. These symptoms have a negative impact on one’s daily life, resulting in fractured relationships, inability to maintain employment, substance abuse, high-cost healthcare utilization, and increased risk of depression and suicide. There are currently around 8 million people diagnosed with PTSD in the US, and healthcare service costs alone are estimated to exceed $8 billion (Wang et al., 2016), highlighting the individual and societal burden of the disorder. 
The current treatments for PTSD include cognitive behavioral therapy and prescription medications such as SSRIs, however treatment is often not tolerated. This is evidenced by low compliance and limited recovery with current medications that may contribute to inability to respond fully to treatment.  Further, existing treatments do little to improve sleep quality of people with PTSD; and sleep disturbances are a well-known treatment-resistant factor which often precipitate or worsen PTSD symptoms (Germain, 2013; Koffel et al., 2013). Therefore, future therapies that improve sleep quality may help to combat the unmet medical need of individuals with PTSD. 
Recent clinical trials looking into the efficacy of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy have shown promising results at both the phase 1 and 2 level, with the FDA granting it Breakthrough Therapy Designation in 2017 (Feduccia et al., 2019). MDMA increases the levels of serotonin, dopamine, and noradrenaline in the brain, which promotes feelings of openness, emotional empathy, and a greater ability to tolerate distressing memories. When these effects are experienced in combination with psychotherapy, MDMA has the ability to augment and enhance one’s inner healing. Interestingly, in Phase 2 trials MDMA-assisted therapy has been shown to improve not only the severity rating scores of PTSD symptoms, but also 63% of participants reported improved sleep quality at long-term follow up (Mithoefer et al., 2011; 2013). 
We sought to explore the relationship between sleep quality and MDMA-assisted therapy and how this could relate to improvements in PTSD symptoms. In the present study, we pooled data from four Phase 2 trials with similar study designs and compared the effects of active dose (75-125mg) MDMA vs control dose (0-40mg) MDMA on PTSD severity and sleep quality. During these studies, participants underwent three 90-min preparatory nondrug therapy sessions, followed by two blinded experimental sessions, spaced 3–5 weeks apart, followed by three 90-min integrative nondrug sessions. We conducted secondary analyses on these data with the hypothesis that improvements in sleep quality, measured by the Pittsburgh Sleep Quality Index (PSQI) would be associated with overall posttreatment PTSD symptom reductions, measured by the Clinician Administered PTSD Scale for DSM-IV (CAPS-IV).

Results showed the following: 

  • Active dose MDMA-assisted therapy significantly improved PTSD symptoms (measured by CAPS-IV severity score) and sleep quality (measured by PSQI) when compared to control (p =0.003 for both outcomes).
  • Over half (53.2%) of the participants in the active group reported a clinically significant improvement in sleep quality, shown by a decrease in PSQI score of 3 points or more (p = 0.003), which was associated with lower scores of PTSD symptom severity.
  • Participants that received an active dose (100-125mg) of MDMA reported improved sleep quality (p = 0.006), required less time to fall asleep (= 0.005), and reported less daytime dysfunction (p = 0.001) than those in the control group. 
  • Significant improvements in both sleep quality and PTSD symptom severity scores were reported at the end of treatment (p = 0.001) which continued to improve further at the 12-month follow-up (p < 0.001).  

Data from these randomized controlled double-blind studies provide evidence for the beneficial effects of MDMA-assisted psychotherapy in treating sleep disturbances in individuals with PTSD. Future research is warranted to further explore the extent to which MDMA impacts both subjective and objective sleep quality, as well as PTSD-associated sleep symptoms. More broadly, this study is yet another milestone in a growing body of research demonstrating the therapeutic benefits of psychedelics.  

Reference/Target Article

Ponte, L., Jerome, L., Hamilton S., Mithoefer M. C., Yazar-Klosinski B. B., Vermetten E. & Feduccia A. A. (2021). Sleep Quality Improvements After MDMA-Assisted Psychotherapy for the Treatment of Posttraumatic Stress Disorder. Journal of Traumatic Stress. 

Discussion Questions

  • Studies have shown that MDMA use may increase insomnia in the short-term. Why might the short-term and long-term effects of MDMA on sleep quality be different?
  • Could improvements in sleep quality explain the enduring therapeutic effect of MDMA-assisted psychotherapy for individuals with PTSD? 
  • What does this mean for the potential use of MDMA-assisted therapy in the context of other mental disorders?

About the Authors

Linnae Ponte, MFT, earned her bachelor’s degree from New College of Florida and master’s degree from the California Institute of Integral Studies. Linnae is the former Director of Harm Reduction for MAPS. Most recently, Linnae gained clinical experience as a facilitator on the psilocybin and MDMA trials taking place at Yale University. 

Lisa Jerome earned a doctorate in psychology from the University of Maryland. Jerome has worked on the creation and revision of MAPS’ Investigator’s Brochure and related documents. She continues to work as an integral part of the Safety team, providing research and informational support to medical monitors and coding data using medical dictionaries.

References Cited:

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. Frontiers in psychiatry10, 650.
Germain, A. (2013). Sleep disturbances as the hallmark of PTSD: where are we now? AJP170, 372–382.
Koffel, E., Polusny, M. A., Arbisi, P. A., & Erbes, C. R. (2013). Pre-deployment daytime and nighttime sleep complaints as predictors of post-deployment PTSD and depression in National Guard troops. Journal of anxiety disorders27(5), 512–519.
Krystal A. D. (2012). Psychiatric disorders and sleep. Neurologic clinics, 30(4), 1389–1413. 
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 Psychopharmacol25(4), 439-452.  
Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T., Jerome, L., Martin, S. F., Yazar-Klosinski, B., Michel, Y., Brewerton, T. D., & 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 Psychopharmacol27(1), 28-39.
Tahmasian, M., Samea, F., Khazaie, H.  Zarei, M., Masouleh, S. K., Hoffstaedter, F., Camilleri, J., Kochunov, P., Yeo, B. T. T., Eickhoff, S. B. & Valk, S. L. (2020). The interrelation of sleep and mental and physical health is anchored in grey-matter neuroanatomy and under genetic control. Commun Biol3, 171. 
Wang, L., Li, L., Zhou, X., Pandya, S. & Baser, O. (2016). A Real-World Evaluation of the Clinical and Economic Burden of United States Veteran Patients with Post-Traumatic Stress Disorder. Value in Health19, A542.