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The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract

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Abstract

Numerous investigations have recently demonstrated the important roles of the endocannabinoid system in the gastrointestinal (GI) tract under physiological and pathophysiological conditions. In the GI tract, cannabinoid type 1 (CB1) receptors are present in neurons of the enteric nervous system and in sensory terminals of vagal and spinal neurons, while cannabinoid type 2 receptors are located in immune cells. Activation of CB1 receptors was shown to modulate several functions in the GI tract, including gastric secretion, gastric emptying and intestinal motility. Under pathophysiological conditions induced experimentally in rodents, the endocannabinoid system conveys protection to the GI tract (e.g. from inflammation and abnormally high gastric and enteric secretions). Such protective activities are largely in agreement with anecdotal reports from folk medicine on the use of Cannabis sativa extracts by subjects suffering from various GI disorders. Thus, the endocannabinoid system may serve as a potentially promising therapeutic target against different GI disorders, including frankly inflammatory bowel diseases (e.g. Crohn’s disease), functional bowel diseases (e.g. irritable bowel syndrome) and secretion- and motility-related disorders. As stimulation of this modulatory system by CB1 receptor agonists can lead to unwanted psychotropic side effects, an alternative and promising avenue for therapeutic applications resides in the treatment with CB1 receptor agonists that are unable to cross the blood–brain barrier, or with compounds that inhibit the degradation of endogenous ligands (endocannabinoids) of CB1 receptors, hence prolonging the activity of the endocannabinoid system.

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Abbreviations

Anandamide:

arachidonoyl ethanolamide

2-AG:

2-arachidonoyl glycerol

AT:

anandamide transporter

CB1:

cannabinoid type 1

CB2:

cannabinoid type 2

FAAH:

fatty acid amide hydrolase

GI:

gastrointestinal

Δ9-THC:

delta-9-tetrahydrocannabinol

TRPV1:

vanilloid type 1

CCK:

cholecystokinin

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Acknowledgements

We wish to thank Drs. Giovanni Marsicano and Krisztina Monory for discussions and suggestions, and Michael Plenikowski for the graphics.

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Authors and Affiliations

  1. Department of Physiological Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 6, 55099, Mainz, Germany

    Federico Massa & Beat Lutz

  2. Department of Internal Medicine II, Ludwig-Maximilians-University Munich, Marchioninistrasse 15, 81377, Munich, Germany

    Martin Storr

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  1. Federico Massa
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  2. Martin Storr
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  3. Beat Lutz
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Correspondence to Beat Lutz.

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Massa, F., Storr, M. & Lutz, B. The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract. J Mol Med 83, 944–954 (2005). https://doi.org/10.1007/s00109-005-0698-5

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  • DOI: https://doi.org/10.1007/s00109-005-0698-5

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