Behavioral Neurobiology of the Endocannabinoid System

Volume 1 of the series Current Topics in Behavioral Neurosciences pp 347-371


Role of Endocannabinoid Signaling in Anxiety and Depression

  • Sachin PatelAffiliated withDepartment of Pharmacology, Medical College of Wisconsin
  • , Cecilia J. HillardAffiliated withDepartment of Pharmacology, Medical College of Wisconsin Email author 

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Cannabinoid receptors and their endogenous ligands are located throughout the limbic, or “emotional,” brain, where they modulate synaptic neurotransmission. Converging preclinical and clinical data suggest a role for endogenous cannabinoid signaling in the modulation of anxiety and depression. Augmentation of endocannabinoid signaling (ECS) has anxiolytic effects, whereas blockade or genetic deletion of CB1 receptors has anxiogenic properties. Augmentation of ECS also appears to have anti-depressant actions, and in some assays blockade and genetic deletion of CB1 receptors produces depressive phenotypes. These data provide evidence that ECS serves in an anxiolytic, and possibly anti-depressant, role. These data suggest novel approaches to treatment of affective disorders which could include enhancement of endogenous cannabinoid signaling, and warrant cautious use of CB1 receptor antagonists in patients with pre-existing affective disorders.


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