Anxiety: Involvement of cannabinergic signaling and cross-talk with serotonergic and opioidergic pathways


Anxiety-related disorders are common in the United States. Anxiety symptoms are treated with benzodiazepines and antidepressants; however, these drugs produce aversive side effects and have nonresponse rates as high as 44%. Researchers have been exploring cannabinoids (CBs) as targets for treating anxiety symptoms. CBs influence behavior through cannabinoid Type I (CB1) receptor signaling. Generally, CB1 receptor agonism and antagonism elicit anxiolytic- and anxiogenic-like behaviors, respectively. However, CBs have dose-dependent biphasic influences on anxiety-related behaviors where higher doses are anxiogenic and lower doses are anxiolytic. CB administration influences anxiety-like behaviors through an array of mechanisms including eliciting changes in hypothalamic-pituitary-adrenal (HPA) axis activity. Additionally, cross-talk and higher-order cross-talk between cannabinergic, serotonergic, and opioidergic pathways have anxiolytic- and/or anxiogenic-like influences on behavior. The goals of this paper are to provide a basic understanding of some of the mechanisms involved in the relationship between anxiety symptoms and CBs and to identify areas that may benefit from further research. This may aid researchers in developing CB pharmacotherapies for anxiety-related symptoms.

Publication Title

Psychology and Neuroscience