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

Abstract

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.

Assessing the Safety and Therapeutic Efficacy of Cannabidiol Lipid Nanoparticles in Alleviating Metabolic and Memory Impairments and Hippocampal Histopathological Changes in Diabetic Parkinson’s Rats

“…According to the preliminary data presented in Figure S1 , the administration of 20 mg/kg CBD-LNP had no significant effect on the locomotor activities of normal rats in the open field test (OFT), while concurrently reducing anxiety levels as observed in the elevated-plus maze. This observation is consistent with previous studies conducted by Costa et al, 2007 and Szulc et al, 2013, which demonstrated the potential of CBD in alleviating inflammatory and neuropathic pain, as well as mitigating alcohol tolerance in rats [ 24 , 25 ]. Therefore, considering the positive outcomes reported in these studies, it was decided to orally administer 20 mg/kg CBD-LNP to DP rats.…”

Natural Products and Health

“…On the molecular level, the most expressed effect of the ethanol-CBD intervention was observed in the striatum, where CBD inverted the ethanol-induced down-regulation of CB2R gene transcription. The opposite effect was observed for the mRNA of CB1 and dopaminergic receptors (DRD1, DRD2) [78].…”