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Erschienen in: Current Treatment Options in Gastroenterology 4/2016

03.10.2016 | Motility (H Parkman and R Schey, Section Editors)

Cannabinoids and GI Disorders: Endogenous and Exogenous

verfasst von: Zachary Wilmer Reichenbach, M.D., Ph.D., Ron Schey, M.D., FACG

Erschienen in: Current Treatment Options in Gastroenterology | Ausgabe 4/2016

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Opinion Statement

Despite the political and social controversy affiliated with it, the medical community must come to the realization that cannabinoids exist as a ubiquitous signaling system in many organ systems. Our understanding of cannabinoids and how they relate not only to homeostasis but also in disease states must be furthered through research, both clinically and in the laboratory. The identification of the cannabinoid receptors in the early 1990s have provided us with the perfect target of translational research. Already, much has been done with cannabinoids and the nervous system. Here, we explore the implications it has for the gastrointestinal tract. Most therapeutics currently on the market presently target only one aspect of the cannabinoid system. Our main purpose here is to highlight areas of research and potential avenues of discovery that the cannabinoid system has yet to reveal.
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Zurück zum Zitat Li XH, Lin ML, Wang ZL, Wang P, Tang HH, Lin YY, Li N, Fang Q, Wang R. Central administrations of hemopressin and related peptides inhibit gastrointestinal motility in mice. Neurogastroenterol Motil. 2016;28:891–9 Explores the use of a novel group of CB 1 R agonists, hemopressin, and their ability to slow GI motility through a CB 1 R dependent manner.PubMedCrossRef Li XH, Lin ML, Wang ZL, Wang P, Tang HH, Lin YY, Li N, Fang Q, Wang R. Central administrations of hemopressin and related peptides inhibit gastrointestinal motility in mice. Neurogastroenterol Motil. 2016;28:891–9 Explores the use of a novel group of CB 1 R agonists, hemopressin, and their ability to slow GI motility through a CB 1 R dependent manner.PubMedCrossRef
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Zurück zum Zitat Wong BS, Camilleri M, Busciglio I, Carlson P, Szarka LA, Burton D, Zinsmeister AR. Pharmacogenetic trial of a cannabinoid agonist shows reduced fasting colonic motility in patients with nonconstipated irritable bowel syndrome. Gastroenterology. 2011;141:1638–47 e1631-1637.PubMedPubMedCentralCrossRef Wong BS, Camilleri M, Busciglio I, Carlson P, Szarka LA, Burton D, Zinsmeister AR. Pharmacogenetic trial of a cannabinoid agonist shows reduced fasting colonic motility in patients with nonconstipated irritable bowel syndrome. Gastroenterology. 2011;141:1638–47 e1631-1637.PubMedPubMedCentralCrossRef
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Zurück zum Zitat Sibaev A, Yüce B, Kemmer M, Van Nassauw L, Broedl U, Allescher HD, Göke B, Timmermans JP, Storr M. Cannabinoid-1 (CB1) receptors regulate colonic propulsion by acting at motor neurons within the ascending motor pathways in mouse colon. Am J Physiol Gastrointest Liver Physiol. 2009;296:G119–28.PubMedCrossRef Sibaev A, Yüce B, Kemmer M, Van Nassauw L, Broedl U, Allescher HD, Göke B, Timmermans JP, Storr M. Cannabinoid-1 (CB1) receptors regulate colonic propulsion by acting at motor neurons within the ascending motor pathways in mouse colon. Am J Physiol Gastrointest Liver Physiol. 2009;296:G119–28.PubMedCrossRef
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Zurück zum Zitat Zhang SC, Wang WL, Su PJ, Jiang KL, Yuan ZW. Decreased enteric fatty acid amide hydrolase activity is associated with colonic inertia in slow transit constipation. J Gastroenterol Hepatol. 2014;29:276–83.PubMedCrossRef Zhang SC, Wang WL, Su PJ, Jiang KL, Yuan ZW. Decreased enteric fatty acid amide hydrolase activity is associated with colonic inertia in slow transit constipation. J Gastroenterol Hepatol. 2014;29:276–83.PubMedCrossRef
75••.
Zurück zum Zitat Bashashati M, Nasser Y, Keenan CM, Ho W, Piscitelli F, Nalli M, Mackie K, Storr MA, Di Marzo V, Sharkey KA. Inhibiting endocannabinoid biosynthesis: a novel approach to the treatment of constipation. Br J Pharmacol. 2015;172:3099–111 In this report, the authors inhibited DAGL and found a resolution of constipation and increased motility. This occurred in a 2-AG and CB 1 R dependent fashion. DAGL remains a very novel area of drug development for the treatment of constipation.PubMedPubMedCentralCrossRef Bashashati M, Nasser Y, Keenan CM, Ho W, Piscitelli F, Nalli M, Mackie K, Storr MA, Di Marzo V, Sharkey KA. Inhibiting endocannabinoid biosynthesis: a novel approach to the treatment of constipation. Br J Pharmacol. 2015;172:3099–111 In this report, the authors inhibited DAGL and found a resolution of constipation and increased motility. This occurred in a 2-AG and CB 1 R dependent fashion. DAGL remains a very novel area of drug development for the treatment of constipation.PubMedPubMedCentralCrossRef
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Zurück zum Zitat Kimball ES, Schneider CR, Wallace NH, Hornby PJ. Agonists of cannabinoid receptor 1 and 2 inhibit experimental colitis induced by oil of mustard and by dextran sulfate sodium. Am J Physiol Gastrointest Liver Physiol. 2006;291:G364–71.PubMedCrossRef Kimball ES, Schneider CR, Wallace NH, Hornby PJ. Agonists of cannabinoid receptor 1 and 2 inhibit experimental colitis induced by oil of mustard and by dextran sulfate sodium. Am J Physiol Gastrointest Liver Physiol. 2006;291:G364–71.PubMedCrossRef
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Zurück zum Zitat Izzo AA, Pinto L, Borrelli F, Capasso R, Mascolo N, Capasso F. Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil. Br J Pharmacol. 2000;129:1627–32.PubMedPubMedCentralCrossRef Izzo AA, Pinto L, Borrelli F, Capasso R, Mascolo N, Capasso F. Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil. Br J Pharmacol. 2000;129:1627–32.PubMedPubMedCentralCrossRef
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Zurück zum Zitat Storr MA, Keenan CM, Emmerdinger D, Zhang H, Yüce B, Sibaev A, Massa F, Buckley NE, Lutz B, Göke B, Brand S, Patel KD, Sharkey KA. Targeting endocannabinoid degradation protects against experimental colitis in mice: involvement of CB1 and CB2 receptors. J Mol Med (Berl). 2008;86:925–36.CrossRef Storr MA, Keenan CM, Emmerdinger D, Zhang H, Yüce B, Sibaev A, Massa F, Buckley NE, Lutz B, Göke B, Brand S, Patel KD, Sharkey KA. Targeting endocannabinoid degradation protects against experimental colitis in mice: involvement of CB1 and CB2 receptors. J Mol Med (Berl). 2008;86:925–36.CrossRef
82••.
Zurück zum Zitat Sałaga M, Mokrowiecka A, Zakrzewski PK, Cygankiewicz A, Leishman E, Sobczak M, Zatorski H, Małecka-Panas E, Kordek R, Storr M, Krajewska WM, Bradshaw HB, Fichna J. Experimental colitis in mice is attenuated by changes in the levels of endocannabinoid metabolites induced by selective inhibition of fatty acid amide hydrolase (FAAH. J Crohns Colitis. 2014;8:998–1009 In this study, the authors employed PF-3845, a FAAH inhibitor, and found that it diminished colitis. Modulating cannabinoid production and degradation exist as promising avenues to capitalize on the ECS without directly utilizing a CB 1 R agonist.PubMedPubMedCentralCrossRef Sałaga M, Mokrowiecka A, Zakrzewski PK, Cygankiewicz A, Leishman E, Sobczak M, Zatorski H, Małecka-Panas E, Kordek R, Storr M, Krajewska WM, Bradshaw HB, Fichna J. Experimental colitis in mice is attenuated by changes in the levels of endocannabinoid metabolites induced by selective inhibition of fatty acid amide hydrolase (FAAH. J Crohns Colitis. 2014;8:998–1009 In this study, the authors employed PF-3845, a FAAH inhibitor, and found that it diminished colitis. Modulating cannabinoid production and degradation exist as promising avenues to capitalize on the ECS without directly utilizing a CB 1 R agonist.PubMedPubMedCentralCrossRef
83••.
Zurück zum Zitat Stančić A, Jandl K, Hasenöhrl C, Reichmann F, Marsche G, Schuligoi R, Heinemann A, Storr M, Schicho R. The GPR55 antagonist CID16020046 protects against intestinal inflammation. Neurogastroenterol Motil. 2015;27:1432–45 The exploration of GPR55 in GI disorders has only started. The authors here utilized a blockage of GPR55 and found that it reduced intestinal inflammation.PubMedPubMedCentralCrossRef Stančić A, Jandl K, Hasenöhrl C, Reichmann F, Marsche G, Schuligoi R, Heinemann A, Storr M, Schicho R. The GPR55 antagonist CID16020046 protects against intestinal inflammation. Neurogastroenterol Motil. 2015;27:1432–45 The exploration of GPR55 in GI disorders has only started. The authors here utilized a blockage of GPR55 and found that it reduced intestinal inflammation.PubMedPubMedCentralCrossRef
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Metadaten
Titel
Cannabinoids and GI Disorders: Endogenous and Exogenous
verfasst von
Zachary Wilmer Reichenbach, M.D., Ph.D.
Ron Schey, M.D., FACG
Publikationsdatum
03.10.2016
Verlag
Springer US
Erschienen in
Current Treatment Options in Gastroenterology / Ausgabe 4/2016
Print ISSN: 1092-8472
Elektronische ISSN: 1534-309X
DOI
https://doi.org/10.1007/s11938-016-0111-1

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