Role of Endocannabinoid Signaling in Anxiety and Depression

  • Sachin Patel
  • Cecilia J. HillardEmail author
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 1)


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.


Cannabis Fatty acid amide hydrolase Post-traumatic stress disorder Marijuana Anandamide Cannabinoid 





5-Hydroxytryptamine, serotonin


Anterior cingulate cortex




Basolateral amygdala




Chronic exposure to an unpredictable and variable set of stressors


Endocannabinoid signaling


Electroconvulsive therapy


Fatty acid amide hydrolase






Prefrontal cortex


Post-traumatic stress disorder


Paraventricular nucleus


Selective serotonin re-uptake inhibitors



CJH was supported during the writing of this review by Research for a Healthier Tomorrow, a component of the Advancing a Healthier Wisconsin endowment at the Medical College of Wisconsin and NIH grant R21 DA022439.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Department of PharmacologyMedical College of WisconsinMilwaukeeUSA

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