Cannabinoids, endocannabinoids and stress

This chapter reviews data that address the hypothesis that CB₁R-endocannabinoid signalling is an important component of the central response to stress. In particular, the available data support the hypothesis that endocannabinoid signalling is altered by stress and that these changes have multiple effects on the time course and degree of the endocrine and sympathetic responses to stress. The effect of chronic unpredictable (variable) stress (CUS) exposure in adult, male mice on the pattern of mRNA expression for components of the endocannabinoid signalling system in various brain regions is presented. The expression of both fatty acid amide hydrolase and monoacylglycerol lipase are significantly reduced by CUS in the hippocampus, as is the expression of the CB₁ receptor. We also present data demonstrating that CUS suppresses CB₁ receptor-mediated regulation of GABA release in the prelimbic region of the medial prefrontal cortex. These data, together with the large body of literature that is reviewed, demonstrate that the endocannabinoid system that was identified as a direct consequence of the identification of Δ⁹-tetrahydrocannabinol plays a vital role in the regulation of the impact of stress on the brain and body. This remarkable and significant role identifies the endocannabinoid system as a potential target for the treatment of many stress-related disorders.