“Background and purpose: Binge drinking is a risky pattern of alcohol intake and a major predictor of alcohol use disorder (AUD). Current AUD medications have limited efficacy and poor patient compliance, calling for more effective therapeutics. Cannabidiol (CBD), a non-intoxicating component of cannabis, has emerged as a potential novel therapeutic. However, receptor mechanisms in CBD’s alcohol-related effects have not been investigated comprehensively.
Experimental approach: Using the murine drinking-in-the-dark model of binge drinking, our research aimed to confirm a reduction of alcohol consumption with CBD (7.5, 15, 30, 60, 120 mg kg-1) in male and female mice. Behavioural pharmacological approaches were used to explore CBD interactions with identified target mechanisms: serotonin-1A receptor (5-HT1AR) and peroxisome proliferator-activated receptor-gamma (PPARɣ), and the novel targets, chemokine receptor type-4 (CXCR4) and neuropeptide S receptor (NPSR).
Key results: Acute CBD dose dependently suppressed binge-like drinking and blood ethanol concentration. The effect was not driven by locomotor impairments and was maintained across sub-chronic treatment. Blockade of 5-HT1AR and PPARɣ had no impact on CBD’s reduction of alcohol consumption. Co-administration of subthreshold CBD doses and a NPSR antagonist implicated NPSR blockade as a potential mechanism contributing to CBD’s effect, whereas co-administration of CBD and a CXCR4 antagonist suggested CXCR4 was not involved. However, the potent and selective CXCR4 antagonist AMD3100 reduced ethanol consumption.
Conclusions and implications: CBD represents a promising candidate to reduce voluntary alcohol consumption. Mechanisms driving CBD’s alcohol-related effects remain unclear and may involve polypharmacology, including actions at the NPSR identified in the present study.”
https://pubmed.ncbi.nlm.nih.gov/40432283/
“These experiments consistently showed a dose-dependent suppression of alcohol consumption by CBD.”
https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.70070