Epigenetic Interactions between Alcohol and Cannabinergic Effects: Focus on Histone Modification and DNA Methylation.

Epigenetic studies have led to a more profound understanding of the mechanisms involved in chronic conditions. In the case of alcohol addiction, according to the National Institute on Alcohol Abuse and Alcoholism, 16 million adults suffer from Alcohol Use Disorders (AUDs). Even though therapeutic interventions like behavioral therapy and medications to prevent relapse are currently available, no robust cure exists, which stems from the lack of understanding the mechanisms of action of alcohol and the lack of development of precision medicine approaches to treat AUDs. Another common group of addictive substance, cannabinoids, have been studied extensively to reveal they work through cannabinoid receptors. Therapeutic applications have been found for the cannabinoids and a deeper understanding of the endocannabinoid system has been gained over the years. Recent reports of cannabinergic mechanisms in AUDs has opened an exciting realm of research that seeks to elucidate the molecular mechanisms of alcohol-induced end organ diseases and hopefully provide insight into new therapeutic strategies for the treatment of AUDs. To date, several epigenetic mechanisms have been associated with alcohol and cannabinoids independently. Therefore, the scope of this review is to compile the most recent literature regarding alcohol and cannabinoids in terms of a possible epigenetic connection between the endocannabinoid system and alcohol effects. First, we will provide an overview of epigenetics, followed by an overview of alcohol and epigenetic mechanisms with an emphasis on histone modifications and DNA methylations. Then, we will provide an overview of cannabinoids and epigenetic mechanisms. Lastly, we will discuss evidence of interactions between alcohol and cannabinergic pathways and possible insights into the novel epigenetic mechanisms underlying alcohol-cannabinergic pathway activity. Finalizing the review will be a discussion of future directions and therapeutic applications.