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Review article: the endocannabinoid system in liver disease, a potential therapeutic target.

Abstract

BACKGROUND

Endocannabinoids are a family of potent lipid-soluble molecules, acting on the cannabinoid (CB) receptors that mediate the effects of marijuana. The CB receptors, endocannabinoids and the enzymes involved in their synthesis and degradation are located in the brain and peripheral tissues, including the liver.

AIMS

To review the current understanding of the role of the endocannabinoid system in liver disease-associated pathophysiological conditions, and drugs targeting the endocannabinoid system as therapy for liver disease.

METHODS

Original articles and reviews were used to summarise the relevant pre-clinical and clinical research findings relating to this topic.

RESULTS

The endocannabinoid system as a whole plays an important role in liver diseases (i.e. non-alcoholic liver disease, alcoholic liver disease, hepatic encephalopathy and autoimmune hepatitis) and related pathophysiological conditions (i.e. altered hepatic haemodynamics, cirrhotic cardiomyopathy, metabolic syndrome and ischaemia/reperfusion disease). Pharmacological targeting of the endocannabinoid system has had success as treatment for patients with liver disease, but adverse events led to withdrawal of marketing approval. However, there is optimism over novel therapeutics targeting the endocannabinoid system currently in the pre-clinical stage of development.

CONCLUSIONS

The endocannabinoid system plays an important role in the pathophysiology of liver disease and its associated conditions. While some drugs targeting the endocannabinoid system have deleterious neurological adverse events, there is promise for a newer generation of therapies that do not cross the blood-brain barrier.

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  • Authors+Show Affiliations

    ,

    Division of Digestive and Liver Diseases and Center for Liver Disease and Transplantation, Columbia University Medical Center, NY, USA; King's County Hospital Medical Center, Brooklyn, NY, USA.

    , ,

    Source

    MeSH

    Animals
    Cannabinoid Receptor Modulators
    Drug Design
    Drug Evaluation, Preclinical
    Endocannabinoids
    Humans
    Liver Diseases
    Molecular Targeted Therapy
    Receptors, Cannabinoid

    Pub Type(s)

    Journal Article
    Review

    Language

    eng

    PubMed ID

    24612021

    Citation

    Basu, P P., et al. "Review Article: the Endocannabinoid System in Liver Disease, a Potential Therapeutic Target." Alimentary Pharmacology & Therapeutics, vol. 39, no. 8, 2014, pp. 790-801.
    Basu PP, Aloysius MM, Shah NJ, et al. Review article: the endocannabinoid system in liver disease, a potential therapeutic target. Aliment Pharmacol Ther. 2014;39(8):790-801.
    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), pp. 790-801. doi:10.1111/apt.12673.
    Basu PP, et al. Review Article: the Endocannabinoid System in Liver Disease, a Potential Therapeutic Target. Aliment Pharmacol Ther. 2014;39(8):790-801. PubMed PMID: 24612021.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Review article: the endocannabinoid system in liver disease, a potential therapeutic target. AU - Basu,P P, AU - Aloysius,M M, AU - Shah,N J, AU - Brown,R S,Jr Y1 - 2014/02/24/ PY - 2013/11/16/received PY - 2013/12/16/revised PY - 2014/02/02/revised PY - 2014/02/03/accepted PY - 2014/3/12/entrez PY - 2014/3/13/pubmed PY - 2014/9/27/medline SP - 790 EP - 801 JF - Alimentary pharmacology & therapeutics JO - Aliment. Pharmacol. Ther. VL - 39 IS - 8 N2 - BACKGROUND: Endocannabinoids are a family of potent lipid-soluble molecules, acting on the cannabinoid (CB) receptors that mediate the effects of marijuana. The CB receptors, endocannabinoids and the enzymes involved in their synthesis and degradation are located in the brain and peripheral tissues, including the liver. AIMS: To review the current understanding of the role of the endocannabinoid system in liver disease-associated pathophysiological conditions, and drugs targeting the endocannabinoid system as therapy for liver disease. METHODS: Original articles and reviews were used to summarise the relevant pre-clinical and clinical research findings relating to this topic. RESULTS: The endocannabinoid system as a whole plays an important role in liver diseases (i.e. non-alcoholic liver disease, alcoholic liver disease, hepatic encephalopathy and autoimmune hepatitis) and related pathophysiological conditions (i.e. altered hepatic haemodynamics, cirrhotic cardiomyopathy, metabolic syndrome and ischaemia/reperfusion disease). Pharmacological targeting of the endocannabinoid system has had success as treatment for patients with liver disease, but adverse events led to withdrawal of marketing approval. However, there is optimism over novel therapeutics targeting the endocannabinoid system currently in the pre-clinical stage of development. CONCLUSIONS: The endocannabinoid system plays an important role in the pathophysiology of liver disease and its associated conditions. While some drugs targeting the endocannabinoid system have deleterious neurological adverse events, there is promise for a newer generation of therapies that do not cross the blood-brain barrier. SN - 1365-2036 UR - https://www.unboundmedicine.com/medline/citation/24612021/Review_article:_the_endocannabinoid_system_in_liver_disease_a_potential_therapeutic_target_ L2 - https://doi.org/10.1111/apt.12673 DB - PRIME DP - Unbound Medicine ER -