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Cannabinoids and the gut: new developments and emerging concepts.

Abstract

Cannabis has been used to treat gastrointestinal (GI) conditions that range from enteric infections and inflammatory conditions to disorders of motility, emesis and abdominal pain. The mechanistic basis of these treatments emerged after the discovery of Delta(9)-tetrahydrocannabinol as the major constituent of Cannabis. Further progress was made when the receptors for Delta(9)-tetrahydrocannabinol were identified as part of an endocannabinoid system, that consists of specific cannabinoid receptors, endogenous ligands and their biosynthetic and degradative enzymes. Anatomical, physiological and pharmacological studies have shown that the endocannabinoid system is widely distributed throughout the gut, with regional variation and organ-specific actions. It is involved in the regulation of food intake, nausea and emesis, gastric secretion and gastroprotection, GI motility, ion transport, visceral sensation, intestinal inflammation and cell proliferation in the gut. Cellular targets have been defined that include the enteric nervous system, epithelial and immune cells. Molecular targets of the endocannabinoid system include, in addition to the cannabinoid receptors, transient receptor potential vanilloid 1 receptors, peroxisome proliferator-activated receptor alpha receptors and the orphan G-protein coupled receptors, GPR55 and GPR119. Pharmacological agents that act on these targets have been shown in preclinical models to have therapeutic potential. Here, we discuss cannabinoid receptors and their localization in the gut, the proteins involved in endocannabinoid synthesis and degradation and the presence of endocannabinoids in the gut in health and disease. We focus on the pharmacological actions of cannabinoids in relation to GI disorders, highlighting recent data on genetic mutations in the endocannabinoid system in GI disease.

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  • Authors+Show Affiliations

    ,

    Department of Experimental Pharmacology, University of Naples Federico II and Endocannabinoid Research Group, Naples, Italy. aaizzo@unina.it

    Source

    Pharmacology & therapeutics 126:1 2010 Apr pg 21-38

    MeSH

    Animals
    Arachidonic Acids
    Cannabinoid Receptor Modulators
    Cannabinoids
    Cannabis
    Dronabinol
    Drug Evaluation, Preclinical
    Drug Tolerance
    Endocannabinoids
    Gastrointestinal Diseases
    Gastrointestinal Tract
    Genetic Variation
    Humans
    Models, Biological
    Polyunsaturated Alkamides
    Receptors, Cannabinoid

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Review

    Language

    eng

    PubMed ID

    20117132

    Citation

    Izzo, Angelo A., and Keith A. Sharkey. "Cannabinoids and the Gut: New Developments and Emerging Concepts." Pharmacology & Therapeutics, vol. 126, no. 1, 2010, pp. 21-38.
    Izzo AA, Sharkey KA. Cannabinoids and the gut: new developments and emerging concepts. Pharmacol Ther. 2010;126(1):21-38.
    Izzo, A. A., & Sharkey, K. A. (2010). Cannabinoids and the gut: new developments and emerging concepts. Pharmacology & Therapeutics, 126(1), pp. 21-38. doi:10.1016/j.pharmthera.2009.12.005.
    Izzo AA, Sharkey KA. Cannabinoids and the Gut: New Developments and Emerging Concepts. Pharmacol Ther. 2010;126(1):21-38. PubMed PMID: 20117132.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cannabinoids and the gut: new developments and emerging concepts. AU - Izzo,Angelo A, AU - Sharkey,Keith A, Y1 - 2010/02/01/ PY - 2009/12/21/received PY - 2009/12/24/accepted PY - 2010/2/2/entrez PY - 2010/2/2/pubmed PY - 2010/6/5/medline SP - 21 EP - 38 JF - Pharmacology & therapeutics JO - Pharmacol. Ther. VL - 126 IS - 1 N2 - Cannabis has been used to treat gastrointestinal (GI) conditions that range from enteric infections and inflammatory conditions to disorders of motility, emesis and abdominal pain. The mechanistic basis of these treatments emerged after the discovery of Delta(9)-tetrahydrocannabinol as the major constituent of Cannabis. Further progress was made when the receptors for Delta(9)-tetrahydrocannabinol were identified as part of an endocannabinoid system, that consists of specific cannabinoid receptors, endogenous ligands and their biosynthetic and degradative enzymes. Anatomical, physiological and pharmacological studies have shown that the endocannabinoid system is widely distributed throughout the gut, with regional variation and organ-specific actions. It is involved in the regulation of food intake, nausea and emesis, gastric secretion and gastroprotection, GI motility, ion transport, visceral sensation, intestinal inflammation and cell proliferation in the gut. Cellular targets have been defined that include the enteric nervous system, epithelial and immune cells. Molecular targets of the endocannabinoid system include, in addition to the cannabinoid receptors, transient receptor potential vanilloid 1 receptors, peroxisome proliferator-activated receptor alpha receptors and the orphan G-protein coupled receptors, GPR55 and GPR119. Pharmacological agents that act on these targets have been shown in preclinical models to have therapeutic potential. Here, we discuss cannabinoid receptors and their localization in the gut, the proteins involved in endocannabinoid synthesis and degradation and the presence of endocannabinoids in the gut in health and disease. We focus on the pharmacological actions of cannabinoids in relation to GI disorders, highlighting recent data on genetic mutations in the endocannabinoid system in GI disease. SN - 1879-016X UR - https://www.unboundmedicine.com/medline/citation/20117132/Cannabinoids_and_the_gut:_new_developments_and_emerging_concepts_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0163-7258(10)00006-9 DB - PRIME DP - Unbound Medicine ER -