The Cannabinoid System as a Potential Novel Target for Alcohol-Associated Liver Disease: A Propensity-Matched Cohort Study
Butros Fakhoury, Vinay Jahagirdar, Kaanthi Rama, David Hudson, Wei Wang, Luis Antonio Díaz, Juan Pablo Arab
| Virginia Commonwealth University, Richmond, Virginia, USA Western University & London Health Sciences Centre, London, Ontario, Canada Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile MASLD Research Center, Division of Gastroenterology and Hepatology, University of California San Diego, San Diego, California, USA Department of Medicine, St. Mary’s Hospital, Waterbury, Connecticut, USA |
Affiliationer
Background
Alcohol-associated liver disease (ALD) is a leading cause of liver-related morbidity and mortality, yet effective therapeutic options remain limited. Preclinical data suggest that modulation of the hepatic endocannabinoid system, particularly via cannabidiol (CBD), may reduce alcohol-induced liver injury. Due to CBD’s limited clinical use, we sought to evaluate the association between cannabis use and ALD risk among patients with alcohol use disorder (AUD).
Methods
Using the TriNetX US Collaborative Network, we identified adult patients with AUD between 2010 and 2022. Three cohorts were constructed: cannabis use disorder (CUD), cannabis users without cannabis abuse or dependence (CU) and non-cannabis users (non-CU). Outcomes included ALD, hepatic decompensation and composite all-cause mortality over 3 years. Incidence and hazard ratios were calculated using Kaplan–Meier analysis and Cox regression.
Results
After matching, 33 114 patients were included in each of the CUD and non-CU groups. Compared to non-CU, CUD was associated with a lower risk of ALD (HR 0.60, 95% CI 0.53–0.67; p < 0.001), hepatic decompensation (HR 0.83, 95% CI 0.73–0.95; p =0.005) and all-cause mortality (HR 0.86, 95% CI 0.80–0.94; p < 0.001) among individuals with AUD. Although CU was associated with lower risks of ALD, its risks of hepatic decompensation and all-cause mortality were similar to those of the non-CU cohort with AUD.
Conclusion
In this propensity-matched cohort study of patients with AUD, cannabis use was associated with a reduced risk of ALD, with the greatest risk reduction seen in patients with CUD compared to CU and non-CU. Our findings suggest that modulation of cannabinoid receptors may offer a new target for the development of pharmacological therapies for ALD.
Summary
- Alcohol-associated liver disease (ALD) is a serious medical condition that has limited therapies available.
- Although cannabidiol has shown promise in experimental studies for reducing alcohol-related liver injury, its clinical use remains limited.
- To address this gap, we evaluated whether cannabis use is associated with a reduced risk of ALD among individuals with alcohol use disorder.
- Cannabis use was linked to lower risks of ALD, liver-related complications and death compared to non-cannabis users.
- These findings suggest the cannabinoid system may represent a promising therapeutic target for ALD.
