Aleksandra Tarasiuka, Maciej Salagaa, and Jakub Fichna
Encyclopedia of Gastroenterology, 2nd Edition, 2019
© 2019 Elsevier Inc. All rights reserved.
Cannabinoids and Their Role in the Physiological and Pathophysiological Processes in the GI Tract 3
Physiological Conditions 3
Gut motility 3
Gastric secretion and emptying 3
Pathophysiological Conditions 4
Colon cancer 5
Peptic ulcer disease 5
Endocannabinoid System and Its Interplay With Other Systems 5
Endocannabinoid System and Gut Microbiota 6
Endocannabinoid system (ECS) is one of the crucial physiological systems that may be targeted to improve human health. Endocannabinoids and their receptors are localized in various organs (heart, lungs, urinary bladder, brain), tissues and cells (e.g., immune cells); they can also be found in the gastrointestinal (GI) tract (Pertwee and Ross, 2002).
ECS consists of cannabinoid receptors type 1 (CB1) and 2 (CB2) which belong to the family of 7-transmembrane receptors, non-CB1 and non-CB2 receptors, their ligands and the enzymes involved in their synthesis, capture and degradation (Storr et al., 2008) (Fig. 1).
Ligands of cannabinoid (CB) receptors include plant-derived compounds (e.g., cannabidiol, cannabinol, yangonin) and synthetic molecules (e.g., drinabant, rimonabant, tedalinab) along with derivatives of arachidonic acid combined with ethanolamine or glycerol, such as anandamide (N arachidonoyl-ethanolamide, AEA), 2-arachidonyglycerol (2-AG), virodhamine (O-arachidonoyl ethanolamine; O-AEA), N-arachidonyldopamine (NADA) and 2-arachidonyl glyceryl ether (noladin ether, 2-AGE) (Sałaga et al., 2018; Ückert et al., 2018). CB1 receptors are located mainly in the brain and the peripheral nervous system, whereas CB2 receptors are mainly found in the immune system and in the central nervous system. Moreover, CB1 receptors are distributed in other sites, such as the GI tract, the circulatory system and the reproductive system (Massa et al., 2004; Pesce et al., 2018; Ückert et al., 2018).
The ECS of the GI tract includes CB receptors and their endogenous agonists as well as tools for their biosynthesis and inactivation.
Literature data indicate that impairment in the regulation of ECS may be a pivotal cause of GI disorders such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and colon cancer (Izzo and Sharkey, 2010; Izzo et al., 2015). This may arise for example from single nucleotide polymorphisms (SNP) in genes of the ECS including fatty acid amide hydrolase (FAAH), the degradative enzyme for the endocannabinoids, and CB1 which are related to increased colonic transit and IBS. In line, it was observed that pharmacological treatment in humans with dronabinol, a synthetic form of delta-9-tetrahydrocannabinol (D9-THC), the primary psychoactive component of cannabis, lowered post-prandial colonic motility. The potency of this therapy was particularly noticeable in patients with single nucleotide polymorphism of FAAH (missense SNP of rs324420 or C385A SNP (Melroy-Greif et al., 2016)) and silent intragenic biallelic polymorphism in codon 435 of the CB1 gene (substitution of G to A at nucleotide position 1359 (1359 G/A rs1049353) (Sadeghian et al., 2018)) (DiPatrizio, 2016). Several other examples can be found in the literature (Kafil et al., 2018; Goyal et al., 2017).
This article discusses the role of ECS and its components in the GI tract physiology as well as GI diseases such as IBS, IBD, colon cancer along with gastric ulcer (Fig. 2).