Role of endocannabinoid signaling in anxiety and depression

Curr Top Behav Neurosci. 2009;1:347-71. doi: 10.1007/978-3-540-88955-7_14.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Anti-Anxiety Agents / therapeutic use
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Anxiety / drug therapy*
  • Anxiety / metabolism
  • Cannabinoid Receptor Modulators / antagonists & inhibitors
  • Cannabinoid Receptor Modulators / deficiency
  • Cannabinoid Receptor Modulators / metabolism*
  • Cannabinoid Receptor Modulators / therapeutic use*
  • Depression / drug therapy*
  • Depression / metabolism
  • Endocannabinoids*
  • Humans
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Signal Transduction / physiology

Substances

  • Anti-Anxiety Agents
  • Antidepressive Agents
  • Cannabinoid Receptor Modulators
  • Endocannabinoids
  • Receptor, Cannabinoid, CB1