HEP (2005) 168:573–598
©cSpringer-Verlag 2005
Cannabinoids and the Digestive Tract
A.A. Izzo^1 ·A.A.Coutts^2 ()
(^1) Department of Experimental Pharmacology, University of Naples Federico II,
via D Montesano 49, 80131 Naples, Italy
(^2) School of Medical Sciences, College of Life Sciences and Medicine, University
of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK
[email protected]
1Introduction.................................... 574
2 The Endogenous Cannabinoid System in the Gut................ 575
3 Gastrointestinal Motility ............................. 577
3.1 InVitroStudies .................................. 578
3.1.1EffectsonExcitatoryNeuronalPathways..................... 578
3.1.2EffectsonInhibitoryNeurotransmission..................... 579
3.2 InVivoStudies................................... 580
3.2.1LowerOesophagealSphincter........................... 580
3.2.2GastricMotility .................................. 581
3.2.3UpperIntestinalMotility ............................. 581
3.2.4MotilityintheColon ............................... 582
4 Intestinal Secretion ................................ 583
5 Gastrointestinal Signs of Tolerance and Dependence .............. 583
6 Cannabinoids in Pathological States....................... 585
6.1 Emesis ....................................... 585
6.2 GastricUlcer ................................... 586
6.3 IntestinalInflammation.............................. 587
6.4 ParalyticIleus ................................... 588
6.5 Diarrhoea(CholeraToxin) ............................ 588
6.6 ColorectalCancer ................................. 589
7 Anandamide as an Endovanilloid ........................ 589
8Conclusion..................................... 591
References ........................................ 592
AbstractIn the digestive tract there is evidence for the presence of high lev-
els of endocannabinoids (anandamide and 2-arachidonoylglycerol) and enzymes
involved in the synthesis and metabolism of endocannabinoids. Immunohisto-
chemical studies have shown the presence of CB 1 receptorsonmyentericand
submucosal nerve plexuses along the alimentary tract. Pharmacological studies
have shown that activation of CB 1 receptors produces relaxation of the lower oe-
sophageal sphincter, inhibition of gastric motility and acid secretion, as well as
intestinal motility and secretion. In general, CB 1 -induced inhibition of intesti-