Interactions Between Alcohol and the Endocannabinoid System

Endocannabinoids are lipid mediators that interact with the same cannabinoid receptors that recognize Δ⁹ -tetrahydrocannabinol (THC), the psychoactive constituent of marijuana, to induce similar effects in the brain and periphery. Alcohol and THC are both addictive substances whose acute use elicits rewarding effects that can lead to chronic and compulsive use via engaging similar signaling pathways in the brain. In the liver, both alcohol and endocannabinoids activate lipogenic gene expression leading to fatty liver disease. This review focuses on evidence accumulated over the last 2 decades to indicate that both the addictive neural effects of ethanol and its organ toxic effects in the liver and elsewhere are mediated, to a large extent, by endocannabinoids signaling via cannabinoid-1 receptors (CB₁ R). The therapeutic potential of CB₁ R blockade globally or in peripheral tissues only is also discussed.