Caryophyllene Oxide is More Potent than Beta Caryophyllene in Attenuating the Abuse‐Related Effects of Ethanol

Abstract

17 million adults in the United States had an alcohol use disorder (AUD) in 2012 and current treatments yield disappointing remission rates. In recent years, the endocannabinoid system has been shown to modulate the abuse‐related effects of ethanol. In this study, we used the loss of righting reflex (LORR) assay to assess the direct pharmacodynamic interactions between beta‐caryophyllene (BCP), its derivative caryophyllene oxide (B Car 21), and ethanol. We investigated the effects of B Car 21 in two widely accepted animal models of ethanol abuse: two bottle choice ethanol consumption and ethanol‐induced conditioned place preference (CPP). Finally, we determined whether there is any pharmacokinetic interaction between B Car 21 and ethanol using blood and brain ethanol analysis. B Car 21 augmented the ethanol‐induced LORR at a dose tenfold lower than BCP. This effect was reversed by pretreatment with a selective CB2 antagonist, AM630. B Car 21 significantly decreased ethanol intake and preference without any effect on total fluid intake in mice that consumed high amounts of ethanol. In mice that consumed low amounts of ethanol, B Car 21 had no effect on ethanol intake, preference, or total fluid intake. B Car 21 significantly attenuated the expression of an ethanol‐induced CPP. Our findings show that B Car 21 is more potent than BCP in vivo and that its attenuation of the abuse‐related effects of ethanol is likely mediated through pharmacodynamic rather than pharmacokinetic interactions. This study expands the support for the CB2 receptor as a viable target for the treatment of AUD.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.