Science Stories

Exploring New Treatment Pathways for Post-Traumatic Stress Disorder

At Jazz, our research and development (R&D) teams are committed to discovering meaningful, differentiated medicines to address the significant unmet need for patients living with life-altering neurological and psychiatric conditions, including post-traumatic stress disorder (PTSD).

PTSD is a common psychiatric condition that can result from direct or indirect exposure to actual or threatened death, serious injury or sexual violence.1 Approximately 70% of the global population will experience a traumatic event at some point during their lifetime, the majority of whom will recover in the days and weeks following trauma exposure.2 However, between 4.7% and 6.1% of Americans who experience such an event will go on to develop PTSD, with similar rates observed across European Union countries (0/6% to 6.7%).3 While men are more likely to experience a traumatic event, women are two times more likely to develop the condition.4

There are four types of PTSD symptoms: recurrent intrusion/re-experiencing, persistent avoidance, negative alterations in mood and cognition, and marked arousal/reactivity. Individuals may experience powerful emotional and physical responses when presented with reminders of the event, experience nightmares, significant sleep disturbance and strong feelings of anger, and feel constantly on edge and watchful of their environment. These symptoms can last long after the trauma occurred.5 PTSD impacts all aspects of patients’ lives including negative impacts on work, school, relationships, housing, legal problems, financial challenges and an overall increase in healthcare utilization and healthcare costs.2,6

Neurobiological models of PTSD are based on a process called fear conditioning. These models suggest that during exposure to a trauma, stress hormones are released in response to fear, which results in strong learning between the cues present at the time of the trauma and the fear response. While this process can be helpful to avoid future danger, the natural recovery process includes a step called extinction learning. During extinction learning, individuals are exposed to reminders and cues of the traumatic event, but in a safe environment to create new learning that these cues are now a signal for safety rather than fear or threat. Dysregulation in this system can lead to continued fear response to these reminders as the cues signal the same level of fear and fear response as the original trauma, underlying the onset and maintenance of PTSD.

Current evidence-based behavioral interventions for PTSD treatment are centered around addressing extinction of this fear response.7 There are also pharmacological treatments, such as selective serotonin reuptake inhibitors, that mitigate some symptoms of PTSD, but these are not designed to address the core underlying problem that transforms such traumatic events and experiences into a chronic mental health illness. Over the past 20 years, there have been only two antidepressants that have received full approval from the U.S. Food and Drug Administration for the treatment of PTSD symptoms.8,9,10

As a long-time leader in providing solutions for patients with limited or no treatment options, we strive to use patient-centric innovation to drive our research and development strategy. This starts with identifying unmet needs across our therapeutic areas of focus and taking the best discovery and development approach to solutions, whether that’s leveraging our proprietary, industry-defining research platforms or our collaborations with leading investigators and bioscience companies. Our commitment to our mid-stage R&D pipeline in neuroscience is demonstrated in our efforts around the MONARCH study.

The study evaluates the safety and efficacy of our investigational first-in-class fatty acid amide hydrolase (FAAH) inhibitor for the treatment of PTSD. Previous studies have shown that FAAH inhibition can improve fear extinction and lessen the effects of stress, offering a possible unique approach to treating PTSD because it targets the pathophysiology of the disorder as opposed to already manifested symptoms.11,12,13,14,15

Our efforts to better understand this devastating disease and research innovative therapies is further evidence of our dedication to provide new treatment options. We’re growing our footprint in neuroscience and with the MONARCH study, we’re adding further diversification to our robust and productive pipeline of innovative mechanism of actions.

Above all else, at Jazz we understand the significant, far-reaching implications of neurological and psychiatric conditions and will continue to expand our understanding of the brain so that we can empower patients to reclaim their lives.


  1. American Psychiatric Association (APA). Diagnostic and Statistical Manual of Mental Disorders. 5th ed. Arlington, VA: American Psychiatric Publishing; 2013.
  2. Kessler RC, Aguilar-Gaxiola S, Alonso J, et al. Trauma and PTSD in the WHO world mental health surveys. Eur J of Psychotraumatol. 2017;8(sup5):1353383.
  3. Burri A and Maercker A. Differences in prevalence rates of PTSD in various European countries explained by war exposure, other trauma and cultural value orientation. BMC Research Notes. 2014;7(1):1-1.
  4. Goldstein RB, Smith SM, Chou SP, et al. The epidemiology of DSM-5 posttraumatic stress disorder in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions-III. Soc Psychiatry Psychiatr Epidemiol. 2016;51(8):1137-48.
  5. American Psychological Association. Post-traumatic Stress Disorder. Accessed December 29, 2021.
  6. Watson P. PTSD as a public mental health priority. Current Psychiatry Reports. 2019;21(7):1-2.
  7. Myers, K., Davis, M. Mechanisms of fear extinction. Mol Psychiatry 12, 120–150 (2007).
  8. Ehret M. Treatment of posttraumatic stress disorder: Focus on pharmacotherapy. Ment Health Clin. 2019;9(6):373-382. Published 2019 Nov 27. doi:10.9740/mhc.2019.11.373
  9. Zoloft® (sertraline hydrochloride) tablets, for oral use. US Prescribing Information. Roerig, New York, NY, US. December 2016.
  10. Paxil® CR (paroxetine) extended-release tablets, for oral use. US Prescribing Information. GlaxoSmithKline, Research Triangle Park, NC, US. September 2019.
  11. Kathuria S, Gaetani S, Fegley D, et al. Modulation of anxiety through blockade of anandamide hydrolysis. Nat Med. 2003;9(1):76-81.
  12. Patel S and Hillard CJ. Pharmacological evaluation of cannabinoid receptor ligands in a mouse model of anxiety: further evidence for an anxiolytic role for endogenous cannabinoid signaling. J Pharmacol Exp Ther. 2006;318(1):304-11.
  13. Mayo LM, Asratian A, Lindé J, et al. Elevated anandamide, enhanced recall of fear extinction, and attenuated stress responses following inhibition of fatty acid amide hydrolase: a randomized, controlled experimental medicine trial. Biol Psychiatry. 2020;87(6):538-47.
  14. D’Souza DC, Cortes-Briones J, Creatura G, et al. Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: a double-blind, placebo-controlled, parallel group, phase 2a single-site randomised controlled trial. The Lancet Psychiatry. 2019;6(1):35-45.
  15. Mayo LM, Asratian A, Lindé J, et al. Protective effects of elevated anandamide on stress and fear-related behaviors: translational evidence from humans and mice. Mol Psychiatry. 2020;25(5):993-1005.