Does Cannabis Intake Protect Against Non-alcoholic Fatty Liver Disease? A Two-Sample Mendelian Randomization Study

Abstract

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Previous observational studies suggested that cannabis use may be associated with a lower risk for NAFLD but the causal relationship remains unclear. We aim in this study to examine the causal effect of cannabis consumption on the risk of NAFLD using a Mendelian randomization analysis. Clarifying this causal effect is important for cannabis-based drug discovery for NAFLD. Methods: We used data from the largest-to-date GWAS meta-analysis on lifetime use of cannabis (yes or no) consisting of three cohorts [International Cannabis Consortium (ICC), 23andMe, and the UK Biobank] of European ancestry (total N = 184,765). We also used other GWAS data on cannabis use dependence and cannabis use disorder (CUD). The NAFLD GWAS data were generated from the UK Biobank population (1,122 cases and 399,900 controls). The inverse variance weighted (IVW) method was used to assess the causal impact of cannabis lifetime use on the risk of NAFLD. We also performed a sensitivity analysis using weighted median estimator and MR-Egger. Results: There was no statistically significant causal effect between either the lifetime cannabis use, cannabis use dependence or CUD and the risk for NAFLD (p > 0.05 for all tests). No significant pleotropic effect was observed based on both MR-PRESSO global test (p = 0.99) and the modified Q' statistics. However, the study may be underpowered. Conclusion: Our results demonstrated no evidence that cannabis consumption has a causal effect of protection against the development of NAFLD.

Expanding Research on Cannabis-Based Medicines for Liver Steatosis: A Low-Risk High-Reward Way Out of the Present Deadlock?

“…Observational studies conducted among cannabis users found a significant inverse relationship between cannabis use and body weight, potentially related to a long-lasting downregulation of CB1, 18 therefore mimicking CB1 blockade. Data regarding cannabis use and liver steatosis tend to display a similar pattern, 19–21 although null effects have occasionally been reported, 22 , 23 as well as isolated negative effects among untreated hepatitis C virus-infected individuals. 24 In addition, protective effects of cannabis use on the occurrence of insulin resistance and diabetes have also been observed in diverse populations.…”

Marijuana use is inversely associated with liver steatosis detected by transient elastography in the general United States population in NHANES 2017–2018: A cross-sectional study

“…Several studies reported that marijuana use is associated with obesity [ 20 ], diabetes [ 21 ], and gastrointestinal diseases [ 22 ]. Hitherto, there has been no consensus on whether marijuana use reduces the prevalence of NAFLD [ 23 , 24 ]. Kim et al conducted an observational study and found that active marijuana use protected against NAFLD through serum alanine aminotransferase levels (n = 14080, OR: 0.76; 95% CI: 0.58–0.98, P = 0.001 for current light users; OR: 0.70; 95% CI: 0.56–0.89, P = 0.001 for current heavy users) and ultrasound diagnosis (n = 8286, OR: 0.77, 95% CI: 0.59–1.00, P = 0.053 for current users; OR: 0.71, 95% CI: 0.51–0.97, P = 0.033 for current light users [ 25 ].…”

THC and CBD affect metabolic syndrome parameters including microbiome in mice fed high fat-cholesterol diet

“…This observation was strengthened by a subsequent clinical trial in which the incidence of liver steatosis was significantly lower in cannabis users (Vázquez-Bourgon et al 2019 ). On the other hand, a conflicting study showed no evidence that cannabis consumption reduces the risk of NAFLD (Wang et al 2020 ). These discrepancies can possibly be explained by the changing chemical profiles found in different cannabis samples.…”