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Alcohol‐use disorder (AUD) is the third leading cause of preventable death in the United States following tobacco and obesity, and current treatments for AUD yield disappointing remission rates. Chronic alcohol intake has been established to negatively impact the body’s immune system, and the endocannabinoid system has been shown to modulate the abuse‐related effects of ethanol. In this study, and we investigated the effects of 30 mg/kg caryophyllene oxide ( BCPO), in two widely accepted animal models of AUD: two‐bottle choice ethanol consumption and ethanol‐induced conditioned place preference (CPP). Finally, we used multiplex bead‐based flow cytometry to evaluate the effect of BCPO on plasma level of cytokines following these behavioral assays. BCPO significantly decreased ethanol intake and preference without changing total fluid intake in mice that consumed high amounts of ethanol. In mice that consumed low amounts of ethanol, BCPO did not alter ethanol intake, preference, or total fluid intake. BCPO significantly attenuated the expression of an ethanol‐induced CPP. Following the CPP assay, we observed a significant decrease in circulating levels of IFNγ, TNFα, MCP1, IL12p70, IL1b, and IL10 which was reversed by treatment with BCPO. Our findings support the current knowledge that excessive consumption of alcohol may lead to immune suppression and predispose individuals to a number of infections as well as neoplastic diseases. This study expands and supports the use of immunoregulatory molecules as a viable target for the treatment of AUD.
