title: Translational evidence for a role of endocannabinoids in the etiology and treatment of posttraumatic stress disorder.
abstract: BACKGROUND
  Posttraumatic stress disorder (PTSD) is a prevalent, chronic, and disabling anxiety disorder that may develop following exposure to a traumatic event. Despite the public health significance of PTSD, relatively little is known about the etiology or pathophysiology of this disorder, and pharmacotherapy development to date has been largely opportunistic instead of mechanism-based. Recently, an accumulating body of evidence has implicated the endocannabinoid system in the etiology of PTSD, and targets within this system are believed to be suitable for treatment development.
  
  
  METHODS
  Herein, we describe evidence from translational studies arguing for the relevance of the endocannabinoid system in the etiology of PTSD. We also show mechanisms relevant for treatment development.
  
  
  RESULTS
  There is convincing evidence from multiple studies for reduced endocannabinoid availability in PTSD. Brain imaging studies show molecular adaptations with elevated cannabinoid type 1 (CB1) receptor availability in PTSD which is linked to abnormal threat processing and anxious arousal symptoms.
  
  
  CONCLUSIONS
  Of particular relevance is evidence showing reduced levels of the endocannabinoid anandamide and compensatory increase of CB1 receptor availability in PTSD, and an association between increased CB1 receptor availability in the amygdala and abnormal threat processing, as well as increased severity of hyperarousal, but not dysphoric symptomatology, in trauma survivors. Given that hyperarousal symptoms are the key drivers of more disabling aspects of PTSD such as emotional numbing or suicidality, novel, mechanism-based pharmacotherapies that target this particular symptom cluster in patients with PTSD may have utility in mitigating the chronicity and morbidity of the disorder.
authors.affiliation: Department of Psychiatry, New York University School of Medicine, New York, NY, USA; Department of Radiology, New York University School of Medicine, New York, NY, USA. Electronic address: alexander.neumeister@nyumc.org.
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumeister
authors.affiliation: Department of Psychiatry, New York University School of Medicine, New York, NY, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Seidel
authors.affiliation: Department of Psychiatry, New York University School of Medicine, New York, NY, USA.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Ragen
authors.affiliation: United States Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, Clinical Neurosciences Division, VA Connecticut Healthcare System, West Haven, CT, USA; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Pietrzak
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000378:metabolism*; D006801:Humans; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy* / Q000209:etiology* / Q000378:metabolism; D057170:Translational Research, Biomedical
chemical_list: D063388:Endocannabinoids; D043884:Receptor, Cannabinoid, CB1
keywords: 5-Factor PTSD model; Anxious arousal; Endocannabinoids; PTSD; Treatment