Reducing Effect of Cannabidiol on Alcohol Self-Administration in Sardinian Alcohol-Preferring Rats

Abstract

Introduction: Cannabidiol (CBD) is a major cannabinoid extracted from Cannabis sativa with no abuse potential. Data from recent rodent studies suggest that amelioration of alcohol-motivated behaviors may be one of the numerous pharmacological effects of CBD. This study was designed to contribute to this research, assessing the effect of CBD on operant oral alcohol self-administration in selectively bred Sardinian alcohol-preferring (sP) rats, a validated animal model of excessive alcohol consumption. In addition, this study investigated the effect of CBD on operant self-administration of a highly palatable chocolate solution in Wistar rats. Materials and Methods: Male sP rats were trained to lever respond for alcohol (15% v/v) under the fixed ratio 4 (FR4) schedule of reinforcement. Once lever responding had stabilized, rats were exposed to test sessions under the FR4 and progressive ratio (PR) schedules of reinforcement. Test sessions were preceded by acute treatment with CBD (0, 6.25, 12.5, and 25 mg/kg or 0, 25, 50, and 100 mg/kg, i.p.; each dose range was tested in an independent experiment). Male Wistar rats were trained to lever respond for a chocolate solution (5% w/v chocolate powder) under the FR10 schedule of reinforcement. Once lever responding had stabilized, rats were exposed to test sessions under the same schedule. Test sessions were preceded by acute treatment with CBD (0, 6.25, 12.5, and 25 mg/kg or 0, 25, 50, and 100 mg/kg, i.p., in two independent experiments). Results: Under the FR schedule, treatment with doses of CBD ‡ 12.5 mg/kg markedly reduced lever responding for alcohol and amount of self-administered alcohol. Under the PR schedule, treatment with CBD produced a slight tendency toward a decrease in lever responding and breakpoint for alcohol. Finally, no dose of CBD affected lever responding for the chocolate solution and amount of self-administered chocolate solution. Discussion: These results extend previous data on CBD ability to affect alcohol-motivated behaviors to an animal model of genetically-determined proclivity to high alcohol consumption. Because of the predictive validity of sP rats, these results may be of relevance in view of possible future studies testing CBD in patients affected by alcohol use disorder.

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

“…Differences in this aspect between these groups of animals indicate that CBD inhibited the development of tolerance to peripheral alcohol effects. This observation is in line with the results of experiments of others, clearly indicating that this compound may influence various aspects of the effects of alcohol, including the possibility of CBD-induced blockade of peripheral hypothermic EtOH activity [ 30 , 34 , 68 ].…”

“…Studies on the interaction of CBD with alcohol have been carried out for years. Briefly, it was found that CBD administration lowered alcohol-drinking behavior in rodent models [ 34 ]. Moreover, it is postulated that its ‘anti-addictive’ action through the regulation of dopaminergic, opioidergic, serotonergic, and endocannabinoid systems, as well as observed in HIP neurogenesis, provides an interesting option for the use of this compound in the treatment of alcoholism [ 35 ].…”

Patterns of Cannabis and Alcohol Co-Use: Substitution Versus Complementary Effects

“… 97 Among these is the treatment of alcohol-related problems and AUD. 98 , 99 Preclinical animal models suggest that CBD dampens preference for alcohol, alcohol seeking, 100 – 102 and alcohol-related functional harms, such as those to the liver and brain. 103 – 106 There is significantly less work examining the effects of CBD on alcohol use in humans.…”

Cannabidiol tempers alcohol intake and neuroendocrine and behavioural correlates in alcohol binge drinking adolescent rats. Focus on calcitonin gene‐related peptide's brain levels

“…These data confirm and extend previous evidence indicating the potential of CBD in attenuating discrete alcohol‐related behaviours in adult rodents (Nona et al, 2019). Indeed, CBD reduced alcohol reinforcement and consummatory behaviour in the two‐bottle choice paradigm, alcohol motivational properties and reinstatement in operant tasks, both in outbred rodents and models of genetically determined excessive alcohol drinking (Gonzalez‐Cuevas et al, 2018; Maccioni et al, 2022; Viudez‐Martínez et al, 2018). Notably, CBD administration was associated with a lower occurrence of high drinking in adolescent rats that decreased their consummatory behaviour for alcohol up to intermediate amounts (Ehinger et al, 2021), thus showing a promising effect in preventing vulnerability to excessive alcohol drinking.…”