Alcohol-Endocannabinoid Interactions: Implications for Addiction-Related Behavioral Processes

PURPOSE: The endogenous cannabinoid system is involved in several physiological functions in the central nervous system including the modulation of brain reward circuitry and emotional homeostasis. Substantial evidence implicates brain endocannabinoid signaling in the processing of drug-induced reward states, wherein repeated exposure besets pathological changes in activity that contribute to the progression of alcohol use disorder. This review provides a narrative summary of recent studies exploring the interaction between alcohol exposure and changes in endocannabinoid signaling that may underlie the development of alcohol use disorder. SEARCH METHODS: The authors began with an initial search for review articles to assist in the identification of relevant literature. This was followed by separate searches for primary literature and recent studies. The search terms “alcohol/ethanol” and “endocannabinoids” were applied, along with terms that covered specific objectives in reinforcement and addiction behavior. The content was further refined by excluding articles containing a broad focus on psychiatric disorders, polysubstance abuse, non-cannabinoid signaling lipids, and other criteria. SEARCH RESULTS: The initial search yielded a total of 49 review articles on PubMed, 13 on ScienceDirect, and 17 on Wiley Online, from which the authors garnered information from a total of 16 reviews. In addition to independent searches, this review provides information from a collection of 212 publications, including reviews and original research articles. DISCUSSION AND CONCLUSIONS: The review discusses the effects of alcohol consumption on brain endocannabinoid signaling, including alcohol-based perturbations in endocannabinoid-mediated synaptic transmission, the modulation of alcohol-related behaviors by manipulating signaling elements of the endocannabinoid system, and the influence of dysregulated endocannabinoid function in promoting withdrawal-induced anxiety-like behavior. Notable emphasis is placed on studies exploring the possible therapeutic relevance of bolstering brain endocannabinoid tone at different stages of alcohol use disorder.