Cannabidiol as a Modulator of the Gut-Liver Axis: Clinical and Pharmacological Insights into Hepatic and Metabolic Disorder Therapies

Abstract

A non-intoxicating substance produced from Cannabis sativa, cannabidiol (CBD) has shown promise as a treatment for metabolic and hepatic diseases, primarily due to its capacity to alter the gut-liver axis. A vital bidirectional communication pathway, the gut-liver axis is where substances produced from the liver affect gut homeostasis and gut-derived microbial products and metabolites influence liver health. Conditions including alcoholic liver disease (ALD), metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD) are mostly caused by dysregulation of this axis. According to preclinical research, CBD has hepatopro-tective benefits via improving the integrity of the gut barrier, decreasing intestinal permea-bility, altering the gut microbiota, and suppressing inflammatory signaling pathways such NF-κB and NLRP3 inflammasome activation. Furthermore, CBD improves insulin sensitivi-ty and lowers hepatic steatosis via modifying lipid and glucose metabolism via the PPARγ and CB1/CB2 receptor pathways. Its antioxidant qualities also help to lessen cellular dam-age and oxidative stress in hepatic tissues. Despite these encouraging results, there is still inconsistency in the clinical data because of variations in dosage, formulation, administra-tion method, and patient-specific variables including liver function and microbiota makeup. Furthermore, broad therapeutic usage is restricted by issues with hepatic metabolism, pos-sible drug-drug interactions, and regulatory obstacles. This review highlights information gaps, critically assesses the available preclinical and clinical evidence, and investigates the mechanisms underlying CBD's impact on the gut-liver axis. Additionally, it identifies po-tential avenues for future optimization of CBD-based therapies targeting liver and metabol-ic illnesses through personalized medicine, sophisticated delivery methods, and standard-ized clinical trial procedures.

Keywords: Cannabidiol; Endocannabinoid System; Gut Micro-biota; Gut-Liver Axis; Hepatic Disorders; Inflammation; Metabolic Syndrome; NAFLD.