The endocannabinoid system plays important roles in liver disease
The endocannabinoid system is involved in multiple liver diseases including fatty liver, alcoholic liver disease, and hepatic encephalopathy, making it a potential therapeutic target despite early drug safety setbacks.
Quick Facts
What This Study Found
This review documented the endocannabinoid system's extensive involvement in liver disease. CB1 and CB2 receptors, endocannabinoids, and their metabolic enzymes are all present in the liver and play roles in multiple conditions including non-alcoholic fatty liver disease, alcoholic liver disease, hepatic encephalopathy, and autoimmune hepatitis.
The system also influences related conditions such as altered liver blood flow, cirrhotic cardiomyopathy, metabolic syndrome, and ischemia/reperfusion injury. One drug targeting the endocannabinoid system (rimonabant, a CB1 blocker) had shown therapeutic success for liver disease but was withdrawn from the market due to serious neurological and psychiatric side effects.
The authors noted optimism about newer therapeutics that target peripheral endocannabinoid receptors without crossing the blood-brain barrier, potentially avoiding the central nervous system side effects that derailed earlier approaches.
Key Numbers
The review covered multiple liver conditions. Rimonabant, the first marketed CB1 blocker, was withdrawn due to adverse psychiatric events. Novel peripherally restricted compounds were in preclinical development.
How They Did This
Review of original articles and reviews summarizing preclinical and clinical research on the endocannabinoid system in liver disease pathophysiology and therapeutic targeting.
Why This Research Matters
Liver disease is a major global health burden, and current treatments are limited for many conditions. The endocannabinoid system offers multiple potential drug targets, but the challenge of avoiding central nervous system side effects has been a significant barrier to drug development.
The Bigger Picture
The rimonabant story is instructive: a drug that worked well for metabolic conditions was pulled because it caused depression and suicidality by blocking CB1 receptors in the brain. The next generation of endocannabinoid-targeting drugs for liver disease aims to affect only peripheral receptors, preserving the brain's endocannabinoid signaling.
What This Study Doesn't Tell Us
Much of the evidence was preclinical. The peripheral-only drug strategy was still in early development at the time of publication. The complexity of the endocannabinoid system in liver pathophysiology makes predicting drug effects challenging.
Questions This Raises
- ?Have peripherally restricted CB1 blockers reached clinical trials for liver disease?
- ?Does cannabis use itself affect liver disease progression?
- ?Can CB2 receptor activation protect the liver without the risks associated with CB1 blockade?
Trust & Context
- Key Stat:
- Endocannabinoid system involved in fatty liver, alcoholic liver disease, hepatic encephalopathy, and more
- Evidence Grade:
- Comprehensive review of mixed preclinical and clinical evidence, with therapeutic applications still largely in development.
- Study Age:
- Published in 2014. Peripherally restricted endocannabinoid-targeting drugs have continued to be developed.
- Original Title:
- Review article: the endocannabinoid system in liver disease, a potential therapeutic target.
- Published In:
- Alimentary pharmacology & therapeutics, 39(8), 790-801 (2014)
- Authors:
- Basu, P P, Aloysius, M M, Shah, N J, Brown, R S
- Database ID:
- RTHC-00766
Evidence Hierarchy
Summarizes existing research on a topic.
What do these levels mean? →Frequently Asked Questions
Does the endocannabinoid system affect liver disease?
Yes. This review documented its involvement in non-alcoholic fatty liver disease, alcoholic liver disease, hepatic encephalopathy, autoimmune hepatitis, and several related conditions. Both CB1 and CB2 receptors play distinct roles in liver pathophysiology.
Why was the CB1 blocker rimonabant withdrawn?
Rimonabant showed therapeutic benefit for metabolic conditions including liver disease, but it crossed the blood-brain barrier and caused serious psychiatric side effects including depression and suicidality, leading to its withdrawal from the market.
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Cite This Study
https://rethinkthc.com/research/RTHC-00766APA
Basu, P P; Aloysius, M M; Shah, N J; Brown, R S. (2014). Review article: the endocannabinoid system in liver disease, a potential therapeutic target.. Alimentary pharmacology & therapeutics, 39(8), 790-801. https://doi.org/10.1111/apt.12673
MLA
Basu, P P, et al. "Review article: the endocannabinoid system in liver disease, a potential therapeutic target.." Alimentary pharmacology & therapeutics, 2014. https://doi.org/10.1111/apt.12673
RethinkTHC
RethinkTHC Research Database. "Review article: the endocannabinoid system in liver disease,..." RTHC-00766. Retrieved from https://rethinkthc.com/research/basu-2014-review-article-the-endocannabinoid
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.