title: Drug discovery strategies that focus on the endocannabinoid signaling system in psychiatric disease.
abstract: BACKGROUND
  The endocannabinoid (eCB) system plays an important role in the control of mood, and its dysregulation has been implicated in several psychiatric disorders. Targeting the eCB system appears to represent an attractive and novel approach to the treatment of depression and other mood disorders. However, several failed clinical trials have diminished enthusiasm for the continued development of eCB-targeted therapeutics for psychiatric disorders, despite the encouraging preclinical data and promising preliminary results obtained with the synthetic cannabinoid nabilone for treating post-traumatic stress disorder.
  
  
  METHODS
  This review describes the eCB system's role in modulating cell signaling within the brain. There is a specific focus on eCB's regulation of monoamine neurotransmission and the stress axis, as well as how dysfunction of this interaction can contribute to the development of psychiatric disorders. Additionally, the review provides discussion on compounds and drugs that target this system and might prove to be successful for the treatment of mood-related psychiatric disorders.
  
  
  CONCLUSIONS
  The discovery of increasingly selective modulators of CB receptors should enable the identification of optimal therapeutic strategies. It should also maximize the likelihood of developing safe and effective treatments for debilitating psychiatric disorders.
authors.affiliation: Drexel University, Department of Pharmacology and Physiology , Mail Stop 400, New College Building, 245 N. 15th Street, Philadelphia, PA 19102 , USA rrw47@drexel.edu.
authors.forename: Ryan
authors.initials: R
authors.lastname: Wyrofsky
authors.forename: Paul
authors.initials: P
authors.lastname: McGonigle
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Van Bockstaele
mesh_terms: D000339:Affect / Q000187:drug effects; D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods*; D063388:Endocannabinoids / Q000378:metabolism*; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D015394:Molecular Structure; D043882:Receptors, Cannabinoid / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism / Q000523:psychology
chemical_list: D014150:Antipsychotic Agents; D063388:Endocannabinoids; D043882:Receptors, Cannabinoid
keywords: CB1 receptors; anxiety; clinical trials; depression; hypothalamic–pituitary–adrenal axis; monoamines; post-traumatic stress disorder; stress response