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Cannabinoid Receptors in Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance

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Gastrointestinal Pharmacology

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 239))

Abstract

Cannabinoid receptors are fundamentally involved in all aspects of intestinal physiology, such as motility, secretion, and epithelial barrier function. They are part of a broader entity, the so-called endocannabinoid system which also includes their endocannabinoid ligands and the ligands’ synthesizing/degrading enzymes. The system has a strong impact on the pathophysiology of the gastrointestinal tract and is believed to maintain homeostasis in the gut by controlling hypercontractility and by promoting regeneration after injury. For instance, genetic knockout of cannabinoid receptor 1 leads to inflammation and cancer of the intestines. Derivatives of Δ9-tetrahydrocannabinol, such as nabilone and dronabinol, activate cannabinoid receptors and have been introduced into the clinic to treat chemotherapy-induced emesis and loss of appetite; however, they may cause many psychotropic side effects. New drugs that interfere with endocannabinoid degradation to raise endocannabinoid levels circumvent this obstacle and could be used in the future to treat emesis, intestinal inflammation, and functional disorders associated with visceral hyperalgesia.

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Abbreviations

2-AG:

2-Arachidonoyl glycerol

Δ9-THC:

Δ9-Tetrahydrocannabinol

AA:

Arachidonic acid

ACEA:

Arachidonyl-2′-chloroethylamide

ACF:

Aberrant crypt foci

AEA:

Arachidonoyl ethanolamine

CB:

Cannabinoid

CBD:

Cannabidiol

CD:

Crohn’s disease

CNS:

Central nervous system

CRC:

Colorectal cancer

DAGL:

Diglyceride-specific lipase

DG:

Diglyceride

ENS:

Enteric nervous system

FAAH:

Fatty acid amide hydrolase

GI:

Gastrointestinal

GPR55:

G protein-coupled receptor 55

IBD:

Inflammatory bowel disease

IBS:

Irritable bowel syndrome

MGL:

Monoglyceride lipase

NANC:

Non-adrenergic non-cholinergic

NAPE:

N-Arachidonoyl phosphatidylethanolamine

NAPE-PLD:

NAPE-selective phospholipase D

OEA:

Oleoylethanolamide

PEA:

Palmitoylethanolamide

PPAR:

Peroxisome proliferative activated receptor

TLESR:

Transient lower esophageal sphincter relaxation

TNFα:

Tumor necrosis factor alpha

TRPV1:

Transient receptor potential cation channel subfamily V member 1

UC:

Ulcerative colitis

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Authors and Affiliations

  1. Institute of Experimental and Clinical Pharmacology, Medical University of Graz, Graz, Austria

    Ulrike Taschler, Carina Hasenoehrl & Rudolf Schicho

  2. Zentrum für Endoskopie, Starnberg, Germany

    Martin Storr

  3. Ludwig-Maximilians University Munich, Marchioninistr. 15, 81377, Munich, Germany

    Martin Storr

Authors
  1. Ulrike Taschler
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  2. Carina Hasenoehrl
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  3. Martin Storr
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  4. Rudolf Schicho
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Correspondence to Martin Storr .

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Editors and Affiliations

  1. Health Sciences Center, The University of Oklahoma, Oklahoma City, Oklahoma, USA

    Beverley Greenwood-Van Meerveld

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Taschler, U., Hasenoehrl, C., Storr, M., Schicho, R. (2016). Cannabinoid Receptors in Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance. In: Greenwood-Van Meerveld, B. (eds) Gastrointestinal Pharmacology . Handbook of Experimental Pharmacology, vol 239. Springer, Cham. https://doi.org/10.1007/164_2016_105

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