Cannabidiol as a Modulator of the Development of Alcohol Tolerance in Rats

The study aimed to explore in vivo the influence of cannabidiol (CBD) on the development of alcohol tolerance in rats. Rats were treated with ethanol (3.0 g/kg, i.p.) and CBD (20 mg/kg, p.o.) for nine successive days, and rectal body temperature, sedation (sleeping time), and blood alcohol concentration (BAC) were measured. In the prefrontal cortex, hippocampus, and striatum, the cannabinoid (CB1R and CB2R) and dopaminergic (DRD1, DRD2, DRD4, DRD5) receptors' mRNA level changes were analyzed using the quantitative RT-PCR method. CBD inhibited the development of tolerance to the hypothermic and sedative action of alcohol, coupled with BAC elevation. On a molecular level, the most pronounced effects of the CBD + ethanol interaction in the striatum were observed, where CBD reversed the downregulation of CB2R gene transcription caused by ethanol. For CB1R, DRD1, and DRD2 mRNAs, the CBD + ethanol interaction produced opposite effects than for CB2R ones. In turn, for the transcription of genes encoding dopaminergic receptors, the most potent effect of alcohol as CBD occurred in the hippocampus. However, the combined CBD and alcohol administration showed the same effect for each substance administered separately. Since tolerance is considered a prelude to drug addiction, obtained results allow us to emphasize the thesis that CBD can inhibit the development of alcohol dependence in rats.