Cannabinoids and Chronic Liver Diseases
Abstract
:1. Introduction
2. Cannabinoids and the Endocannabinoid System (eCBS)
2.1. The eCBS
2.2. Phytocannabinoids
3. The Endocannabinoid System in Chronic Liver Diseases
3.1. Hepatic Endocannabinoid System in Normal Physiology
3.2. Hepatic Endocannabinoid System in NAFLD and NASH
3.3. Hepatic Endocannabinoid System in ALD
3.4. The Hepatic Endocannabinoid System in Chronic Viral Hepatitis
4. Impact of Cannabis Intake and Cannabinoid-Based Medicine on NAFLD, NASH, ALD, and HCV-Induced Liver Disorders: Evidence from Preclinical, Observational, and Clinical-Trial Studies
4.1. Cannabis Use and CLD
4.1.1. Cannabis Use and NAFLD and NASH
4.1.2. Cannabis Use and ALD
4.1.3. Cannabis Use and HCV/HBV-Associated CLD
4.2. Cannabinoid-Based Medicine and CLDs
5. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Conflicts of Interest
References
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Main Outcomes and Conclusions | Study Design and Methodology | References |
---|---|---|
Cannabidiol | ||
| In vivo mice model of segmental hepatic ischemia. | [29] |
| In vitro and in vivo models of hepatic fibrosis. | [30] |
| In vitro and in vivo models of alcohol-induced liver steatosis. | [31] |
| In vitro and in vivo models of hepatosteatosis. Transcriptional, posttranslational, and metabolomic assays. | [32] |
|
| [33] |
| Mice-liver-injury model induced by ethanol plus high-fat high-cholesterol diet (EHFD) for 8 weeks. | [34] |
| Randomized double-blind placebo-controlled study: 5 treatment arms: CBD alone (100 mg twice daily); THCV alone (5 mg twice daily); 1:1 ratio of CBD and THCV (5 mg/5 mg, twice daily); 20:1 ratio of CBD and THCV (100 mg/5 mg, twice daily); or matched placebo for 13 weeks, on 62 subjects with noninsulin-treated type 2 diabetes. | [35] |
| Randomized partially blind placebo-controlled dose-ranging phase 2 clinical study: 200/400/800 mg of CBD daily or placebo for 8 weeks on 25 participants with NAFLD. | [36] |
Tetrahydrocannabivarin | ||
| In vivo model of fasting and feeding mice. | [37] |
| In vitro and in vivo mice models of hepatic ischemia. | [38] |
| In vivo mice model of diet-induced obesity (DIO) treated with regimens of increasing doses of THCV:
| [39] |
| In vitro and in vivo models of hepatosteatosis. Transcriptional, posttranslational, and metabolomic assays. | [32] |
| Randomized double-blind placebo-controlled study: 5 treatment arms: CBD alone (100 mg twice daily); THCV alone (5 mg twice daily); 1:1 ratio of CBD and THCV (5 mg/5 mg, twice daily); 20:1 ratio of CBD and THCV (100 mg/5 mg, twice daily); matched placebo for 13 weeks, on 62 subjects with noninsulin-treated type 2 diabetes. | [35] |
Tetrahydrocannabinolic acid | ||
| In vitro functional assay and in vivo mice model of high fat diet (HFD)-induced obesity. | [40] |
| In vitro model of liver fibrosis and in vivo ice model of nonalcoholic liver fibrosis induced by CCl4 treatment of 23-weeks of high-fat-diet (HFD) feeding. | [41] |
Atypical Cannabinoid Abn-CBD | ||
| Diet-induced obese mouse model of prediabetes and nonalcoholic fatty liver disease (NAFLD). | [42] |
Main Outcome | Study Design | Participant Characteristics | Method to Assess Outcome | Reference |
---|---|---|---|---|
NAFLD/NASH | ||||
Cannabis use is associated with lower prevalence of NAFLD/NASH. | Population-based case–control study | A total of 5,950,391 patients, 18 years and older, in three groups: noncannabis users (98.04%), nondependent cannabis users (1.74%), and dependent cannabis users (0.22%). | Multivariate logistic regression to determine the odds of developing NAFLD with respect to cannabis use. | [83] |
Cannabis use is associated with lower levels of fasting insulin and insulin resistance. | Examination survey | 4657 adults aged 18 years and older | Fasting insulin and glucose measured via blood samples after a 9 h fast, and HOMA-IR calculated to evaluate insulin resistance. Multiple linear regression to determine associations. | [84] |
Prevalence of obesity is lower in cannabis users than in nonusers. | Cross-sectional data on 2 population-based nationally representative studies. | 52,375 adults aged 18 years or older | Logistic regression model with obesity as a categorical outcome, and the frequency of cannabis use in the past year as the primary association. | [85] |
Inverse association between cannabis use and obesity. | Population-based 3-year prospective study. | 43,093 adults aged 18 years or older | General linear modeling yields estimates for change in body-mass index regressed on cannabis-use status. | [86] |
Current marijuana use is associated with lower odds of metabolic syndrome across emerging and middle-aged adults. | Population-based 5-year prospective study | 8478 adults, 20–59 years old | Metabolic syndrome was defined as ≥ 3 of the following: elevated fasting glucose, high triglycerides, low high-density-lipoprotein cholesterol, elevated systolic/diastolic blood pressure, and increased waist circumference. An age-stratified analysis was conducted to examine the relationship between marijuana use and metabolic syndrome among emerging adults (20–30 years), adults (31–44 years), and middle-aged adults (45–59 years). | [87] |
Marijuana use was independently associated with a lower prevalence of diabetes mellitus. | Cross-sectional study | 10,896 adults, 20–59 years old | Univariate and multivariate logistic regression analyses were used to determine the relationship between diabetes mellitus and marijuana use. | [88] |
Active marijuana use provided a protective effect against NAFLD independent of known metabolic risk factors. | Cross-sectional data from 2 National Health and Nutrition Examination Surveys | 22,366 | NAFLD was defined either by a serum alanine aminotransferase (ALT) that was >30 IU/L for men and >19 IU/L for women in the absence of other liver diseases, or based on ultrasonography. | [89] |
ALD | ||||
Among alcohol users, cannabis use was associated with significantly lower odds of developing alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. | Cross-sectional data from National Health and Nutrition Examination Survey | 319,514 adults 18 years and older | Univariate and multivariate logistic regression analyses were used to determine the relationship between alcoholic steatosis, steatohepatitis, fibrosis, cirrhosis, hepatocellular carcinoma, and cannabis use. | [90] |
No association between cannabis use and advanced liver fibrosis in heavy alcohol drinkers. | Cross-sectional study | 248 HIV-positive individuals with heavy alcohol use | Transient elastography was used to detect advanced liver fibrosis among participants. | [91] |
HCV/HBV infection | ||||
Regular or daily cannabis use was associated with a reduced risk of an elevated fatty liver index in HIV–HCV-coinfected individuals. | 5-year longitudinal study | 997 HIV–HCV-coinfected individuals | Mixed-effects multivariable logistic and linear regression models | [92] |
Cannabis use was associated with lower risks of obesity in chronically HBV-infected individuals. | Cross-sectional study | 3706 chronically HBV-infected individuals | Logistic and multinomial regression analyses | [93] |
Cannabis use was independently associated with a lower risk of diabetes in chronically HCV-infected individuals. | Cross-sectional study | 10,445 chronically HCV-infected individuals | Multivariate logistic regression analyses | [94] |
Daily cannabis use was independently associated with a reduced prevalence of steatosis. | Cross-sectional study in a nationwide multicenter cohort | 838 adults, HIV–HCV-coinfected individuals | A logistic regression model was used to evaluate the association between cannabis use and steatosis. | [95] |
THC-rich cannabis use was not associated with progression to significant liver fibrosis. | 11-year longitudinal study | 575 HIV–HCV-coinfected women | Cox proportional hazards regression analysis | [96] |
Cannabis use is associated with a lower insulin-resistance risk in HIV–HCV-coinfected individuals. | 60-month longitudinal study | 703 HIV–HCV-coinfected individuals | A mixed-effects multivariable logistic regression model | [97] |
Daily cannabis smoking is significantly associated with fibrosis progression during chronic hepatitis C virus infection. | Cross-sectional study | 270 untreated chronically hepatitis-infected individuals | Multivariate stepwise logistic regression analyses | [98] |
Daily cannabis smoking as a novel independent predictor of steatosis severity during chronic hepatitis C virus infection. | Cross-sectional study | 315 untreated chronically hepatitis-infected individuals | Multivariate stepwise logistic regression analyses | [99] |
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Mboumba Bouassa, R.-S.; Sebastiani, G.; Di Marzo, V.; Jenabian, M.-A.; Costiniuk, C.T. Cannabinoids and Chronic Liver Diseases. Int. J. Mol. Sci. 2022, 23, 9423. https://doi.org/10.3390/ijms23169423
Mboumba Bouassa R-S, Sebastiani G, Di Marzo V, Jenabian M-A, Costiniuk CT. Cannabinoids and Chronic Liver Diseases. International Journal of Molecular Sciences. 2022; 23(16):9423. https://doi.org/10.3390/ijms23169423
Chicago/Turabian StyleMboumba Bouassa, Ralph-Sydney, Giada Sebastiani, Vincenzo Di Marzo, Mohammad-Ali Jenabian, and Cecilia T. Costiniuk. 2022. "Cannabinoids and Chronic Liver Diseases" International Journal of Molecular Sciences 23, no. 16: 9423. https://doi.org/10.3390/ijms23169423