Role of Endocannabinoid Signaling in Anxiety and Depression

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.

Keywords

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

Abbreviations

2AG

2-Arachidonoylglycerol

5-HT

5-Hydroxytryptamine, serotonin

ACC

Anterior cingulate cortex

AEA

Anandamide

BLA

Basolateral amygdala

CCK

Cholecystokinin

CUS

Chronic exposure to an unpredictable and variable set of stressors

ECS

Endocannabinoid signaling

ECT

Electroconvulsive therapy

FAAH

Fatty acid amide hydrolase

HPA

Hypothalamus–pituitary–adrenal

KO

Knockout

PFC

Prefrontal cortex

PTSD

Post-traumatic stress disorder

PVN

Paraventricular nucleus

SSRI

Selective serotonin re-uptake inhibitors

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  1. 1.Department of PharmacologyMedical College of WisconsinMilwaukeeUSA

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