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

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2020-02, Vol.44 (2), p.340-353
• Main Authors: Karoly, Hollis C., Mueller, Raeghan L., Bidwell, L. Cinnamon, Hutchison, Kent E.
• Format: Article
• Language: English
• Subjects: Alcohol use; Alcoholism - drug therapy; Alcoholism - metabolism; Animals; Brain - drug effects; Brain - metabolism; Cannabidiol; Cannabidiol - metabolism; Cannabidiol - pharmacology; Cannabidiol - therapeutic use; Cannabinoids; Cannabinoids - metabolism; Cannabinoids - pharmacology; Cannabinoids - therapeutic use; Cognitive ability; Digestive system; Endocannabinoid; Endocannabinoid system; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - physiology; Gastrointestinal tract; Gastrointestinal Tract - drug effects; Gastrointestinal Tract - metabolism; Gut‐microbiota; Humans; Immune system; Intestinal microflora; Intestine; Microbiota; Permeability; Therapeutic applications
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/acer.14256

The endocannabinoid system (ECS) has emerged in recent years as a potential treatment target for alcohol use disorders (AUD). In particular, the nonpsychoactive cannabinoid cannabidiol (CBD) has shown preclinical promise in ameliorating numerous clinical symptoms of AUD. There are several proposed mechanism(s) through which cannabinoids (and CBD in particular) may confer beneficial effects in the context of AUD. First, CBD may directly impact specific brain mechanisms underlying AUD to influence alcohol consumption and the clinical features of AUD. Second, CBD may influence AUD symptoms through its actions across the digestive, immune, and central nervous systems, collectively known as the microbiota–gut–brain axis (MGBA). Notably, emerging work suggests that alcohol and cannabinoids exert opposing effects on the MGBA. Alcohol is linked to immune dysfunction (e.g., chronic systemic inflammation in the brain and periphery) as well as disturbances in gut microbial species (microbiota) and increased intestinal permeability. These MGBA disruptions have been associated with AUD symptoms such as craving and impaired cognitive control. Conversely, existing preclinical data suggest that cannabinoids may confer beneficial effects on the gastrointestinal and immune system, such as reducing intestinal permeability, regulating gut bacteria, and reducing inflammation. Thus, cannabinoids may exert AUD harm‐reduction effects, at least in part, through their beneficial actions across the MGBA. This review will provide a brief introduction to the ECS and the MGBA, discuss the effects of cannabinoids (particularly CBD) and alcohol in the brain, gut, and immune system (i.e., across the MGBA), and put forth a theoretical framework to inform future research questions. The endocannabinoid system, and particularly the non‐psychoactive cannabinoid cannabidiol (CBD), has emerged in recent years as a potential treatment target for alcohol use disorders (AUD). This critical review discusses the hypothesized effects of CBD on neural mechanisms underlying AUD, as well as across the microbiota‐gut‐brain axis (MGBA). Emerging work suggests that alcohol and cannabinoids (e.g., CBD) exert opposing effects on the MGBA. Thus, cannabinoids may exert AUD harm‐reduction effects, at least in part, through their beneficial actions across the MGBA.