Cannabidiol as a Novel Candidate Alcohol Use Disorder Pharmacotherapy: A Systematic Review

Abstract

There is substantial interest in the therapeutic potential of cannabidiol (CBD), a nonpsychoactive cannabinoid found in plants of the genus Cannabis. The goal of the current systematic review was to characterize the existing literature on this topic and to evaluate the credibility of CBD as a candidate pharmacotherapy for alcohol use disorder (AUD). Using a comprehensive search strategy, 303 unique potential articles were identified and 12 ultimately met criteria for inclusion (8 using rodent models, 3 using healthy adult volunteers, and 1 using cell culture). In both rodent and cell culture models, CBD was found to exert a neuroprotective effect against adverse alcohol consequences on the hippocampus. In rodent models, CBD was found to attenuate alcohol-induced hepatotoxicity, specifically, alcoholinduced steatosis. Finally, findings from preclinical rodent models also indicate that CBD attenuates cue-elicited and stress-elicited alcohol seeking, alcohol self-administration, withdrawal-induced convulsions, and impulsive discounting of delayed rewards. In human studies, CBD was well tolerated and did not interact with the subjective effects of alcohol. Collectively, given its favorable effects on alcoholrelated harms and addiction phenotypes in preclinical models, CBD appears to have promise as a candidate AUD pharmacotherapy. This is further bolstered by the absence of abuse liability and its general tolerability. A clear limitation to the literature is the paucity of human investigations. Human preclinical and clinical studies are needed to determine whether these positive effects in model systems substantively translate into clinically relevant outcomes.

Cannabis and Alcohol: From Basic Science to Public Policy

“…Cannabis research has lagged behind that of alcohol research, but important studies are emerging on the interactions between alcohol and cannabinoids. In this Virtual Issue, Cannabis and Alcohol: From Basic Science to Public Policy , we present 9 leading‐edge research publications spanning preclinical and epidemiological studies, as well as a critical review of the potential therapeutic use of cannabidiol (CBD) in the treatment of alcohol use disorder (AUD) (Turna et al., ), which recently appeared in Alcoholism: Clinical and Experimental Research .…”

“…In contrast, cannabis produces anti‐inflammatory actions (Nair et al., ), and it is of great interest to determine if any of the detrimental effects of alcohol can be ameliorated by exo‐ or endocannabinoids. As discussed in this Virtual Issue, studies in animal models report protective effects of CBD on alcohol‐induced neurodegeneration and alcohol‐induced liver steatosis, and human studies suggest a relationship between co‐use of cannabis and alcohol on immune function and inflammation (Karoly et al., ; Turna et al., ). To further examine cannabis–alcohol interactions in humans, Karoly and colleagues () determined if plasma levels of proinflammatory cytokines were associated with alcohol and cannabis use.…”

“…CBD has become widely available in many forms from a rapidly increasing number of online and retail suppliers. Preclinical studies reviewed by Turna and colleagues () in this Virtual Issue report diverse beneficial effects of CBD, such as neuroprotection from adverse alcohol effects in the hippocampus and reduced alcohol‐mediated liver damage, as well as reduced alcohol‐dependent phenotypes (e.g., alcohol self‐administration, craving, acute withdrawal). While only a few studies have examined the effects of CBD and alcohol in humans, the clinical evidence indicates that CBD was well tolerated and did not interact with the subjective effects of alcohol (Turna et al., ).…”

Cannabinoids and the Microbiota–Gut–Brain Axis: Emerging Effects of Cannabidiol and Potential Applications to Alcohol Use Disorders

“…Emerging evidence suggests that CBD may mitigate symptoms of AUD (Turna et al, ). CBD reduces the reinforcing properties of alcohol and decreases drinking motivation and consumption in mice (Viudez‐Martínez et al, , ) and attenuates cue‐induced and stress‐induced alcohol seeking, reinstatement, anxiety, and impulsivity in a rat model of AUD (Gonzalez‐Cuevas et al, ).…”

“…In sum, existing evidence indicates that THC may have synergistic or no effects in combination with alcohol, but CBD may mitigate cognitive impairment, lessen subjective effects of alcohol, and reduce relapse vulnerability across several domains. Further, CBD is well tolerated in humans, has no abuse liability, and does not interact with the subjective effects of alcohol, indicating that it could be a promising AUD treatment or harm‐reduction option (Turna et al, ). Thus, a logical next step is for human laboratory studies is to directly explore the impact of CBD on alcohol consumption both in an acute laboratory setting and over time.…”