Skip to main content
SpringerLink
Log in
Book cover

Cannabinoids pp 573–598Cite as

Cannabinoids and the Digestive Tract

  • Chapter

Part of the Handbook of Experimental Pharmacology book series (HEP,volume 168)

Abstract

In the digestive tract there is evidence for the presence of high levels of endocannabinoids (anandamide and 2-arachidonoylglycerol) and enzymes involved in the synthesis and metabolism of endocannabinoids. Immunohistochemical studies have shown the presence of CB1 receptors on myenteric and submucosal nerve plexuses along the alimentary tract. Pharmacological studies have shown that activation of CB1 receptors produces relaxation of the lower oesophageal sphincter, inhibition of gastric motility and acid secretion, as well as intestinal motility and secretion. In general, CB1-induced inhibition of intestinal motility and secretion is due to reduced acetylcholine release from enteric nerves. Conversely, endocannabinoids stimulate intestinal primary sensory neurons via the vanilloid VR1 receptor, resulting in enteritis and enhanced motility. The endogenous cannabinoid system has been found to be involved in the physiological control of colonic motility and in some pathophysiological states, including paralytic ileus, intestinal inflammation and cholera toxin-induced diarrhoea. Cannabinoids also possess antiemetic effects mediated by activation of central and peripheral CB1 receptors. Pharmacological modulation of the endogenous cannabinoid system could provide a new therapeutic target for the treatment of a number of gastrointestinal diseases, including nausea and vomiting, gastric ulcers, secretory diarrhoea, paralytic ileus, inflammatory bowel disease, colon cancer and gastro-oesophageal reflux conditions.

Keywords

  • Cannabinoid receptors
  • Intestinal motility
  • Intestinal secretion
  • Emesis
  • Intestinal inflammation
  • Feeding

This is a preview of subscription content, access via your institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   549.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   699.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adami M, Frati P, Bertini S, Kulkarni-Narla A, Brown DR, de Caro G, Coruzzi G, Soldani G (2002) Gastric antisecretory role and immunohistochemical localization of cannabinoid receptors in the rat stomach. Br J Pharmacol 135:1598–1606

    CrossRef  PubMed  CAS  Google Scholar 

  • Ahluwalia J, Urban L, Capogna M, Bevan S, Nagy I (2000) Cannabinoid 1 receptors are expressed in nociceptive primary sensory neurons. Neuroscience 100:685–688

    CrossRef  PubMed  CAS  Google Scholar 

  • Akiba Y, Nakamura M, Ishii H (2001) Immunolocalization of vanilloid receptor-1 (VR-1) in CGRP-positive neurons and interstitial cells of Cajal in the myenteric plexus of the rat gastrointestinal tract. Gastroenterology 120:1721

    Google Scholar 

  • Anavi-Goffer S, Coutts AA (2003) Cellular distribution of vanilloid VR1 receptor immunoreactivity in the guinea-pig myenteric plexus. Eur J Pharmacol 458:61–71

    CrossRef  PubMed  CAS  Google Scholar 

  • Anavi-Goffer S, McKay MG, Ashford MLJ, Coutts AA (2002) Vanilloid receptor type 1-immunoreactivity is expressed by intrinsic afferent neurones in the guinea-pig myenteric plexus. Neurosci Lett 319:53–57

    CrossRef  PubMed  CAS  Google Scholar 

  • Anderson PF, Jackson DM, Chesher GB, Malor R (1975) Tolerance to the effects of delta-9-tetrahydrocannabinol in mice on intestinal motility, temperature and locomotor activity. Psychopharmacologia 43:31–36

    CrossRef  PubMed  CAS  Google Scholar 

  • Bartho L, Benko R, Lazar Z, Illenyi L, Horvath OP (2002) Nitric oxide is involved in the relaxant effect of capsaicin in the human sigmoid colon circular muscle. Naunyn Schmiedebergs Arch Pharmacol 366:496–500

    PubMed  CAS  Google Scholar 

  • Basilico L, Parolaro D, Colleoni M, Costa B, Giagnoni G (1999) Cross-tolerance and convergent dependence between morphine and cannabimimetic agent WIN 55,212-2 in the guinea-pig ileum myenteric plexus. Eur J Pharmacol 376:265–271

    CrossRef  PubMed  CAS  Google Scholar 

  • Bateman DN (1983) Delta-9-tetrahydrocannabinol and gastric emptying. Br J Clin Pharmacol 15:749–751

    PubMed  CAS  Google Scholar 

  • Begg M, Dale N, Llaudet E, Molleman A, Parsons ME (2002a) Modulation of the release of endogenous adenosine by cannabinoids in the myenteric preparation of the guinea-pig plexus-longitudinal muscle ileum. Br J Pharmacol 137:1298–1304

    CrossRef  PubMed  CAS  Google Scholar 

  • Begg M, Molleman A, Parsons M (2002b) Modulation of the release of endogenous gamma-aminobutyric acid by cannabinoids in the guinea pig ileum. Eur J Pharmacol 434:87–94

    CrossRef  PubMed  CAS  Google Scholar 

  • Bifulco M, Di Marzo V (2002) Targeting the endocannabinoid system in cancer therapy: a call for further research. Nat Med 8:547–550

    CrossRef  PubMed  CAS  Google Scholar 

  • Brown DR, Poonyachoti S, Osinski MA, Kowalski TR, Pampusch MS, Elde RP, Murtaugh MP (1998) Delta-opioid receptor mRNA expression and immunohistochemical localization in porcine ileum. Dig Dis Sci 43:1402–1410

    CrossRef  PubMed  CAS  Google Scholar 

  • Burdyga G, Lal S, Varro A, Dimaline R, Thompson DG, Dockray GJ (2004) Expression of cannabinoid CB1 receptors by vagal afferent neurons is inhibited by cholecystokinin. J Neurosci 24:2708–2715

    CrossRef  PubMed  CAS  Google Scholar 

  • Calignano A, La Rana G, Makriyannis A, Lin SY, Beltramo M, Piomelli D (1997) Inhibition of intestinal motility by anandamide, an endogenous cannabinoid. Eur J Pharmacol 340:R7–R8

    PubMed  CAS  Google Scholar 

  • Capasso R, Izzo AA, Fezza F, Pinto A, Capasso F, Mascolo N, Di Marzo V (2001) Inhibitory effect of palmitoylethanolamide on gastrointestinal motility in mice. Br J Pharmacol 134:945–950

    CrossRef  PubMed  CAS  Google Scholar 

  • Casu MA, Porcella A, Ruiu S, Saba P, Marchese G, Carai MA M, Reali R, Gessa GL, Pani L (2003) Differential distribution of functional cannabinoid CB1 receptors in the mouse gastroenteric tract. Eur J Pharmacol 459:97–105

    CrossRef  PubMed  CAS  Google Scholar 

  • Chesher GB, Dahl CJ, Everingham M, Jackson DM, Marchant Williams H, Starmer GA (1973) The effect of cannabinoids on intestinal motility and their antinociceptive effect in mice. Br J Pharmacol 49:588–594

    PubMed  CAS  Google Scholar 

  • Colombo G, Agabio R, Lobina C, Reali R, Gessa GL (1998) Cannabinoid modulation of intestinal propulsion in mice. Eur J Pharmacol 344:67–69

    CrossRef  PubMed  CAS  Google Scholar 

  • Coruzzi G, Adami M, Coppelli G, Frati P, Soldani G (1999) Inhibitory effect of the cannabinoid receptor agonist WIN 55,212-2 on pentagastrin-induced gastric acid secretion in the anaesthetized rat. Naunyn Schmiedebergs Arch Pharmacol 360:715–718

    CrossRef  PubMed  CAS  Google Scholar 

  • Coutts AA (2004) Cannabinoid receptor activation and the endocannabinoid system in the gastrointestinal tract. Curr Neuropharmacol 2:91–102

    CAS  Google Scholar 

  • Coutts AA, Pertwee RG (1997) Inhibition by cannabinoid receptor agonists of acetylcholine release from the guinea-pig myenteric plexus. Br J Pharmacol 121:1557–1566

    PubMed  CAS  Google Scholar 

  • Coutts AA, Brewster N, Ingram T, Razdan RK, Pertwee RG (2000) Comparison of novel cannabinoid partial agonists and SR141716A in the guinea-pig small intestine. Br J Pharmacol 129:645–652

    CrossRef  PubMed  CAS  Google Scholar 

  • Coutts AA, Irving AJ, Mackie K, Pertwee RG, Anavi-Goffer S (2002) Localisation of cannabinoid CB1 receptor immunoreactivity in the guinea pig and rat myenteric plexus. J Comp Neurol 448:410–422

    CrossRef  PubMed  CAS  Google Scholar 

  • Croci T, Manara L, Aureggi, Guagnini F, Rinaldi-Carmona M, Maffrand J-P, Le Fur G, Mukenge S, Ferla G (1998) In vitro functional evidence of neuronal cannabinoid CB1 receptors in human ileum. Br J Pharmacol 125:1393–1395

    CrossRef  PubMed  CAS  Google Scholar 

  • Croci T, Landi M, Galzin AM, Marini P (2003) Role of cannabinoid CB1 receptors and tumor necrosis factor-alpha in the gut and systemic anti-inflammatory activity of SR 141716 (Rimonabant) in rodents. Br J Pharmacol 140:115–122

    CrossRef  PubMed  CAS  Google Scholar 

  • Darmani NA (2001a) Delta(9)-tetrahydrocannabinol and synthetic cannabinoids prevent emesis produced by the cannabinoid CB1 receptor antagonist/inverse agonist SR141716A. Neuropsychopharmacology 24:198–203

    CrossRef  PubMed  CAS  Google Scholar 

  • Darmani NA (2001b) The cannabinoid CB1 receptor antagonist SR 141716A reverses the antiemetic and motor depressant actions of WIN 55, 212-2. Eur J Pharmacol 430:49–58

    CrossRef  PubMed  CAS  Google Scholar 

  • Darmani NA (2002) The potent emetogenic effects of the endocannabinoid, 2-AG (2-arachidonoylglycerol) are blocked by delta(9)-tetrahydrocannabinol and other cannabinoids. J Pharmacol Exp Ther 300:34–42

    CrossRef  PubMed  CAS  Google Scholar 

  • Darmani NA, Janoyan JJ, Kumar N, Crim JL (2003a) Behaviorally active doses of the CB1 receptor antagonist SR 141716A increase brain serotonin and dopamine levels and turnover. Pharmacol Biochem Behav 75:777–787

    CrossRef  PubMed  CAS  Google Scholar 

  • Darmani NA, Sim-Selley LJ, Martin BR, Janoyan JJ, Crim JL, Parekh B, Breivogel CS (2003b) Antiemetic and motor-depressive actions of CP55,940: cannabinoid CB1 receptor characterization, distribution, and G-protein activation. Eur J Pharmacol 459:83–95

    CrossRef  PubMed  CAS  Google Scholar 

  • De Petrocellis L, Cascio MG, Di Marzo V (2004) The endocannabinoid system: a general view and latest additions. Br J Pharmacol 141:765–774

    CrossRef  PubMed  CAS  Google Scholar 

  • Dewey WL, Harris LS, Kennedy JS (1972) Some pharmacological and toxicological effects of l-trans-delta-8-and l-trans-delta-9-tetrahydrocannabinol in laboratory rodents. Arch Int Pharmacodyn Ther 196:133–145

    PubMed  CAS  Google Scholar 

  • Di Carlo G, Izzo AA (2003) Cannabinoids for gastrointestinal diseases: potential therapeutic applications. Expert Opin Investig Drugs 12:39–49

    CrossRef  PubMed  Google Scholar 

  • Facer P, Knowles CH, Tam PK H, Ford AP, Dyer N, Baecker PA, Anand P (2001) Novel capsaicin (VR1) and purinergic (P2X(3)) receptors in Hirschsprung’s intestine. J Pediatr Surg 36:1679–1684

    CrossRef  PubMed  CAS  Google Scholar 

  • Feher E, Vajda J (1982) Effect of capsaicin on the nerve elements of the small intestine. Acta Morphol Acad Sci Hung 30:57–63

    PubMed  CAS  Google Scholar 

  • Frederickson RC A, Hewes CR, Aiken JW (1976) Correlation between the in vivo and in vitro expression of opiate withdrawal precipitated by naloxone: their antagonism by l-(-)-delta-9-tetrahydrocannabinol. J Pharmacol Exp Ther 199:375–384

    PubMed  CAS  Google Scholar 

  • Germanò MP, D’Angelo V, Mondello R, Pergolizzi S, Capasso F, Capasso R, Izzo AA, Mascolo N, De Pasquale R (2001) Cannabinoid CB1-mediated inhibition of stress-induced gastric ulcers in rats. Naunyn Schmiedebergs Arch Pharmacol 363:241–244

    PubMed  Google Scholar 

  • Gomez R, Navarro M, Ferrer B, Trigo JM, Bilbao A, Del Arco I, Cippitelli A, Nava F, Piomelli D, Rodriguez de Fonseca F (2002) A peripheral mechanism for CB1 cannabinoid receptor-dependent modulation of feeding. J Neurosci 22:9612–9617

    PubMed  CAS  Google Scholar 

  • Griffin G, Fernando SR, Ross RA, McKay NG, Ashford MLJ, Shire D, Huffman JW, Yu S, Lainton JA H, Pertwee RG (1997) Evidence for the presence of CB2-like cannabinoid receptors on peripheral nerve terminals. Eur J Pharmacol 339:53–61

    CrossRef  PubMed  CAS  Google Scholar 

  • Guanini F, Croci T, Aureggi G, Manara L, Rinaldi-Carmona M, Mukenge S, Aldrighetti L, Ferla G, Maffrand J-P, Le Fur G (2000) Tolerance to (+)WIN55,212-2 inhibitory effect and withdrawal by the cannabinoid CB1 receptor antagonist SR 141716 in isolated strips of small intestine. International Cannabinoid Research Society symposium on the Cannabinoids, Burlington, Vermont

    Google Scholar 

  • Hanus L, Abu-Lafi S, Fride E, Breuer A, Vogel Z, Shalev DE, Kustanovich I, Mechoulam R (2001) 2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc Natl Acad Sci USA 98:3662–3665

    CrossRef  PubMed  CAS  Google Scholar 

  • Heinemann A, Shahbazian A, Holzer P (1999) Cannabinoid inhibition of guinea-pig intestinal peristalsis via inhibition of excitatory and activation of inhibitory neural pathways. Neuropharmacology 38:1289–1297

    CrossRef  PubMed  CAS  Google Scholar 

  • Heshmati H, Caplain H, Bellisle F, Mosse M, Fauveau C, Le Fur G (2001) SR141716, a selective CB1 receptor cannabinoid receptor antagonist reduces hunger, caloric intake, and body weight in overweight or obese men. Obes Res 9:70S

    Google Scholar 

  • Hine B, Friedman E, Torrelio M, Gershon S (1975) Morphine-dependent rats: blockade of precipitated abstinence by tetrahydrocannabinol. Science 187:443–445

    PubMed  CAS  Google Scholar 

  • Holzer P (2001) Gastrointestinal afferents as targets of novel drugs for the treatment of functional bowel disorders and visceral pain. Eur J Pharmacol 429:177–193

    CrossRef  PubMed  CAS  Google Scholar 

  • Holzer P (2003) Acid-sensitive ion channels in gastrointestinal function. Curr Opin Pharmacol 3:618–625

    PubMed  CAS  Google Scholar 

  • Ihenetu K, Molleman A, Parsons ME, Whelan CJ (2003) Inhibition of interleukin-8 release in the human colonic epithelial cell line HT-29 by cannabinoids. Eur J Pharmacol 458:207–215

    CrossRef  PubMed  CAS  Google Scholar 

  • Izzo AA, Mascolo N, Borrelli F, Capasso F (1998) Excitatory transmission to the circular muscle of the guinea-pig ileum: evidence for the involvement of cannabinoid CB1 receptors. Br J Pharmacol 124:1363–1368

    PubMed  CAS  Google Scholar 

  • Izzo AA, Mascolo N, Capasso R, Germano MP, DePasquale R, Capasso F (1999a) Inhibitory effect of cannabinoid agonists on gastric emptying in the rat. Naunyn Schmiedebergs Arch Pharmacol 360:221–223

    CrossRef  PubMed  CAS  Google Scholar 

  • Izzo AA, Mascolo N, Borrelli F, Capasso F (1999b) Defaecation, intestinal fluid accumulation and motility in rodents: implications of cannabinoid CB1 receptors. Naunyn Schmiedebergs Arch Pharmacol 359:65–70

    PubMed  CAS  Google Scholar 

  • Izzo AA, Mascolo N, Tonini M, Capasso F (2000) Modulation of peristalsis by cannabinoid CB1 ligands in the isolated guinea-pig ileum. Br J Pharmacol 129:984–990

    PubMed  CAS  Google Scholar 

  • Izzo AA, Pinto L, Borrelli F, Capasso R, Mascolo N, Capasso F (2000b) Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil. Br J Pharmacol 129:1627–1632

    PubMed  CAS  Google Scholar 

  • Izzo AA, Capasso R, Pinto L, Di Carlo G, Mascolo N, Capasso F (2001a) Effect of vanilloid drugs on gastrointestinal transit in mice. Br J Pharmacol 132:1411–1416

    CrossRef  PubMed  CAS  Google Scholar 

  • Izzo AA, Fezza F, Capasso R, Bisogno T, Pinto L, Iuvone T, Esposito G, Mascolo N, Di Marzo V, Capasso F (2001b) Cannabinoid CB1-receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation. Br J Pharmacol 134:563–570

    CrossRef  PubMed  CAS  Google Scholar 

  • Izzo AA, Mascolo N, Capasso F (2001c) The gastrointestinal pharmacology of cannabinoids. Curr Opin Pharmacol 1:597–603

    PubMed  CAS  Google Scholar 

  • Izzo AA, Capasso F, Costagliola A, Bisogno T, Marsicano G, Ligresti A, Matias I, Capasso R, Pinto L, Borrelli F, Cecio A, Lutz B, Mascolo N, Di Marzo V (2003) An endogenous cannabinoid tone attenuates cholera toxin-induced fluid accumulation in mice. Gastroenterology 125:765–774

    CrossRef  PubMed  CAS  Google Scholar 

  • Joseph J, Niggemann B, Zaenker KS, Entschladen F (2004) Anandamide is an endogenous inhibitor for the migration of tumor cells and T lymphocytes. Cancer Immunol Immunother 53:723–728

    CrossRef  PubMed  CAS  Google Scholar 

  • Katayama K, Ueda N, Kurahashi Y, Suzuki H, Yamamoto S, Kato I (1997) Distribution of anandamide amidohydrolase in rat tissues with special reference to small intestine. Biochim Biophys Acta 1347:212–218

    PubMed  CAS  Google Scholar 

  • Kojima S, Sugiura T, Waku K K, Kamikawa Y (2002) Contractile response to a cannabimimetic eicosanoid, 2-arachidonoylglycerol, of longitudinal smoothmuscle from the guinea-pig distal colon in vitro. Eur J Pharmacol 444:203–207

    CrossRef  PubMed  CAS  Google Scholar 

  • Krowicki ZK, Moerschbaecher JM, Winsauer PJ, Digavalli SV, Hornby PJ (1999) Delta9-tetrahydrocannabinol inhibits gastric motility in the rat through cannabinoid CB1 receptors. Eur J Pharmacol 371:187–196

    CrossRef  PubMed  CAS  Google Scholar 

  • Kulkarni-Narla A, Brown DR (2000) Localization of CB1-cannabinoid receptor immunoreactivity in the porcine enteric nervous system. Cell Tissue Res 302:73–80

    CrossRef  PubMed  CAS  Google Scholar 

  • Kulkarni-Narla A, Brown DR (2001) Opioid, cannabinoid and vanilloid receptor localization on porcine cultured myenteric neurons. Neurosci Lett 308:153–156

    CrossRef  PubMed  CAS  Google Scholar 

  • Kwiatkowska M, Parker LA, Burton P, Mechoulam R (2004) A comparative analysis of the potential of cannabinoids and ondansetron to supress cisplatin-induced emesis in the Suncus murinus (house musk shrew). Psychopharmacology (Berl). 174:254–259

    CrossRef  PubMed  CAS  Google Scholar 

  • Lambert DM, Vandevoorde S, Jonsson KO, Fowler CJ (2002) The palmitoylethanolamide family: A new class of anti-inflammatory agents? Curr Med Chem 9:663–674

    PubMed  CAS  Google Scholar 

  • Landi M, Croci T, Rinaldi-Carmona M, Maffrand JP, Le Fur G, Manara L (2002) Modulation of gastric emptying and gastrointestinal transit in rats through intestinal cannabinoid CB1 receptors. Eur J Pharmacol 450:77–83

    CrossRef  PubMed  CAS  Google Scholar 

  • Lee MC, Smith FL, Stevens DL, Welch SP (2003) The role of several kinases in mice tolerant to Delta(9)-tetrahydrocannabinol. J Pharmacol Exp Ther 305:593–599

    PubMed  CAS  Google Scholar 

  • Lehmann A, Blackshaw LA, Branden L, Carlsson A, Jensen J, Nygren E, Smid SD (2002) Cannabinoid receptor agonism inhibits transient lower esophageal sph incter relaxations and reflux in dogs. Gastroenterology 123:1129–1134

    CrossRef  PubMed  CAS  Google Scholar 

  • Ligresti A, Bisogno T, Matias I, De Petrocellis L, Cascio MG, Cosenza V, D’Argenio G, Scaglione G, Bifulco M, Sorrentini I, Di Marzo V (2003) Possible endocannabinoid control of colorectal cancer growth. Gastroenterology 125:677–687

    CrossRef  PubMed  CAS  Google Scholar 

  • López-Redondo F, Lees GM, Pertwee RG (1997) Effects of cannabinoid receptor ligands on electrophysiological properties of myenteric neurones of the guinea-pig ileum. Br J Pharmacol 122:330–334

    PubMed  Google Scholar 

  • Lundgren O (2002) Enteric nerves and diarrhoea. Pharmacol Toxicol 90:109–120

    CrossRef  PubMed  CAS  Google Scholar 

  • Lynn AB, Herkenham M (1994) Localization of cannabinoid receptors and nonsaturable high-density cannabinoid binding sites in peripheral tissues of the rat: implications for receptor-mediated immune modulation by cannabinoids. J Pharmacol Exp Ther 268:1612–1623

    PubMed  CAS  Google Scholar 

  • MacNaughton WK, Cushing K, Van Sickle MD, Keenan CM, Mackie K, Sharkey KA (2003) Cannabinoid CB1 receptor distribution and function in neurally mediated chloride secretion in the guinea pig ileum. Gastroenterology 124:A342

    Google Scholar 

  • MacNaughton WK, Van Sickle MD, Keenan CM, Cushing K, Mackie K, Sharkey KA (2004) Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves. Am J Physiol Gastrointest Liver Physiol (in press)

    Google Scholar 

  • Manara L, Croci T, Guagnini F, Rinaldi-Carmona M, Maffrand JP, Le Fur G, Mukenge S, Ferla G (2002) Functional assessment of neuronal cannabinoid receptors in the muscular layers of human ileum and colon. Dig Liver Dis 34:262–269

    CrossRef  PubMed  CAS  Google Scholar 

  • Mancinelli R, Fabrizi A, Del Monaco S, Azzena GB, Vargiu R, Colombo GC, Gessa GL (2001) Inhibition of peristaltic activity by cannabinoids in the isolated distal colon of mouse. Life Sci 69:101–111

    CrossRef  PubMed  CAS  Google Scholar 

  • Mang CF, Erbelding D, Kilbinger H (2001) Differential effects of anandamide on acetylcholine release in the guinea-pig ileum mediated via vanilloid and non-CB1 cannabinoid receptors. Br J Pharmacol 134:161–167

    CrossRef  PubMed  CAS  Google Scholar 

  • Mascolo N, Izzo AA, Ligresti A, Costagliola A, Pinto L, Cascio MG, Maffia P, Cecio A, Capasso F, Di Marzo V (2002) The endocannabinoid system and the molecular basis of paralytic ileus in mice. Faseb J 16:1973–1975

    PubMed  CAS  Google Scholar 

  • Massa F, Marsicano G, Hermann H, Cannich A, Krisztina M, Cravatt BF, Ferri G-L, Sibaev A, Lutz B (2004) The endogenous cannabinoid system protects against colonic inflammation. J Clin Invest 113:1202–1209

    CrossRef  PubMed  CAS  Google Scholar 

  • McCallum RW, Soykan I, Sridhar KR, Ricci DA, Lange RC, Plankey MW (1999) Delta-9-tetrahydrocannabinol delays the gastric emptying of solid food in humans: a double-blind, randomized study. Aliment Pharmacol Ther 13:77–80

    CrossRef  PubMed  CAS  Google Scholar 

  • McVey DC, Schmid PC, Schmid HH O, Vigna SR (2003) Endocannabinoids induce ileitis in rats via the capsaicin receptor (VR1). J Pharmacol Exp Ther 304:713–722

    CrossRef  PubMed  CAS  Google Scholar 

  • Morrone LA, Romanelli L, Mazzanti G, Valeri P, Menichin F (1993) Hashish antagonism on the in vitro development of withdrawal contracture. Pharmacol Res 27(Suppl 1):63–64

    CAS  Google Scholar 

  • Nye JS, Seltzman HH, Pitt CG, Snyder SH (1985) High affinity cannabinoid binding sites in brain membranes labeled with [H-3]-5-trimethylammonium delta-8-tetra-hydrocannabinol. J Pharmacol Exp Ther 234:784–791

    PubMed  CAS  Google Scholar 

  • Oleinik VM (1995) Distribution of digestive enzyme activities along intestine in blue fox mink, ferret and rat. Comp Biochem Physiol A Physiol 112:55–58

    PubMed  CAS  Google Scholar 

  • Parker LA, Mechoulam R (2003) Cannabinoid agonists and antagonists modulate lithium-induced conditioned gaping in rats. Integr Physiol Behav Sci 38:134–146

    Google Scholar 

  • Parker LA, Mechoulam R, Schlievert C (2002) Cannabidiol, a non-psychoactive component of cannabis and its synthetic dimethylheptyl homolog suppress nausea in an experimental model with rats. Neuroreport 13:567–570

    PubMed  CAS  Google Scholar 

  • Parker LA, Mechoulam R, Schlievert C, Abbott L, Fudge ML, Burton P (2003) Effects of cannabinoids on lithium-induced conditioned rejection reactions in a rat model of nausea. Psychopharmacology (Berl) 166:156–162

    PubMed  CAS  Google Scholar 

  • Partosoedarso ER, Abrahams TP, Scullion RT, Moerschbaecher JM, Hornby PJ (2003) Cannabinoid1 receptor in the dorsal vagal complex modulates lower oesophageal sphincter relaxation in ferrets. J Physiol 550:149–158

    CrossRef  PubMed  CAS  Google Scholar 

  • Paton WDM, Zar MA (1968) The origin of acetylcholine released from guinea-pig intestine and longitudinal muscle strips. J Physiol (Lond) 194:13–33

    PubMed  CAS  Google Scholar 

  • Pertwee RG (1997) Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther 74:129–180

    CrossRef  PubMed  CAS  Google Scholar 

  • Pertwee RG (2001) Cannabinoids and the gastrointestinal tract. Gut 48:859–867

    CrossRef  PubMed  CAS  Google Scholar 

  • Pertwee RG, Ross RA (2002) Cannabinoid receptors and their ligands.Prostaglandins Leukot Essent Fatty Acids 66:101–121

    CrossRef  PubMed  CAS  Google Scholar 

  • Pertwee RG, Stevenson LA, Elrick DB, Mechoulam R, Corbett AD (1992) Inhibitory effects of certain enantiomeric cannabinoids in the mouse vas deferens and themyenteric plexus preparation of guinea-pig small intestine. Br J Pharmacol 105:980–984

    PubMed  CAS  Google Scholar 

  • Pertwee RG, Fernando SR, Griffin G, Abadji V, Makriyannis A (1995) Effect of phenylmethyl-sulphonyl fluoride on the potency of anandamide as an inhibitor of electrically evoked contractions in two isolated tissue preparations. Eur J Pharmacol 272:73–78

    PubMed  CAS  Google Scholar 

  • Pertwee RG, Fernando SR, Nash JE, Coutts AA (1996) Further evidence for the presence of cannabinoid CB1 receptors in guinea-pig small intestine. Br J Pharmacol 118:2199–2205

    PubMed  CAS  Google Scholar 

  • Pertwee RG, Fernando S, Ritchie JEA (1998) Preliminary validation of a novel experimental model for the study of cannabinoid tolerance. International Cannabinoid Research Society symposium on the Cannabinoids, Burlington, Vermont

    Google Scholar 

  • Pinto L, Capasso R, Di Carlo G, Izzo AA (2002a) Endocannabinoids and the gut. Prostaglandins Leukot Essent Fatty Acids 66:333–341

    CrossRef  PubMed  CAS  Google Scholar 

  • Pinto L, Izzo AA, Cascio MG, Bisogno T, Hospodar-Scott K, Brown DR, Mascolo N, Di Marzo VCapasso F (2002b) Endocannabinoids as physiological regulators of colonic propulsion in mice. Gastroenterology 123:227–234

    CrossRef  PubMed  CAS  Google Scholar 

  • Poonyachoti S, Kulkarni-Narla A, Brown DR (2002) Chemical coding of neurons expressing delta-and kappa-opioid receptor and type I vanilloid receptor immunoreactivities in the porcine ileum. Cell Tissue Res 307:23–33

    CrossRef  PubMed  CAS  Google Scholar 

  • Rosell S, Agurell S (1975) Effects of 7-hydroxy-D6-tetrahydrocannabinol and some related cannabinoids on the guinea-pig isolated ileum. Acta Physiol Scand 94:142–144

    CrossRef  PubMed  CAS  Google Scholar 

  • Rosell S, Agurell S, Martin BR (1976) Effects of cannabinoids on isolated smooth muscle preparations. New York, Springer-Verlag

    Google Scholar 

  • Ross RA, Brockie HC, Fernando SR, Saha B, Razdan RK, Pertwee RG (1998) Comparison of cannabinoid binding sites in guinea-pig forebrain and small intestine. Br J Pharmacol 125:1345–1351

    CrossRef  PubMed  CAS  Google Scholar 

  • Rumessen JJ, d’Exaerde AD, Mignon S, Bernex F, Timmermans JP, Schiffmann SN, Panthier JJ, Vanderwinden JM (2001) Interstitial cells of Cajal in the striated musculature of the mouse esophagus. Cell Tissue Res 306:1–14

    CrossRef  PubMed  CAS  Google Scholar 

  • Shire D, Carillon C, Kaghad M, Calandra B, Rinaldi-Carmona M, Le Fur G, Caput D, Ferrara P (1995) An amino-terminal variant of the central cannabinoid receptor resulting from alternative splicing. J Biol Chem 270:3726–3731

    PubMed  CAS  Google Scholar 

  • Shook JE, Burks TF (1989) Psychoactive cannabinoids reduce gastrointestinal propulsion and motility in rodents. J Pharmacol Exp Ther 249:444–449

    PubMed  CAS  Google Scholar 

  • Simoneau II, Hamza MS, Mata HP, Siegel EM, Vanderah, TW, Porreca F, Makriyannis A, Malan TP (2001) The cannabinoid agonist WIN55,212-2 suppresses opioid-induced emesis in ferrets. Anesthesiology 94:882–887

    PubMed  CAS  Google Scholar 

  • Sofia RD, Diamantis W, Harrison JE, Melton J (1978) Evaluation of antiulcer activity of delta-9-tetrahydrocannabinol in the Shay rat test. Pharmacology 17:173–177

    PubMed  CAS  Google Scholar 

  • Storr M, Gaffal E, Saur D, Schusdziarra V, Allescher HD (2002) Effect of cannabinoids on neural transmission in rat gastric fundus. Can J Physiol Pharmacol 80:67–76

    PubMed  CAS  Google Scholar 

  • Storr M, Sibaev A, Marsicano G, Lutz B, Schusdziarra V, Timmermans JP Allescher HD (2004) Cannabinoid receptor type 1 modulates excitatory and inhibitory neurotransmission in mouse colon. Am J Physiol Gastrointest Liver Physiol 286:G110–G117

    PubMed  CAS  Google Scholar 

  • Sugiura T, Kobayashi Y, Oka S, Waku K (2002) Biosynthesis and degradation of anandamide and2-arachidonoylglycerol andtheirpossiblephysiological significance. Prostaglandins Leukot Essent Fatty Acids 66:173–192

    CrossRef  PubMed  CAS  Google Scholar 

  • Todorov S, Pozzoli C, Zamfirova R, Poli E (2003) Prejunctional modulation of non-adrenergic non-cholinergic (NANC) inhibitory responses in the isolated guinea-pig gastric fundus. Neurogastroenterol Motil 15:299–306

    CrossRef  PubMed  CAS  Google Scholar 

  • Tominaga M, Wada M, Masu M (2001) Potentiation of capsaicin receptor activity by metabotropic ATP receptors as a possible mechanism for ATP-evoked pain and hyperalgesia. Proc Natl Acad Sci U S A 98:6951–6956

    CrossRef  PubMed  CAS  Google Scholar 

  • Tramer MR, Carroll D, Campbell FA, Reynolds DJM, Moore RA, McQuay HJ (2001) Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review. Br Med J 323:16–21

    CAS  Google Scholar 

  • Tyler K, Hillard CJ, Greenwood-Van Meerveld B (2000) Inhibition of small intestinal secretion by cannabinoids is CB1 receptor-mediated in rats. Eur J Pharmacol 409:207–211

    CrossRef  PubMed  CAS  Google Scholar 

  • Ueda N, Yamamoto S (2000) Anandamide amidohydrolase (fatty acid amide hydrolase). Prostaglandins Other Lipid Mediat 61:19–28

    PubMed  CAS  Google Scholar 

  • Van Sickle MD, Oland LD, Ho, W, Hillard CJ, Mackie K, Davison JS, Sharkey KA (2001) Cannabinoids inhibit emesis through CB1 receptors in the brainstem of the ferret. Gastroenterology 121:767–774

    PubMed  Google Scholar 

  • Van Sickle MD, Oland LD, Mackie K, Davison JS, Sharkey KA (2003) Delta-9–tetrahydrocannabinol selectively acts on cannabinoid 1(CB1) receptors in specific regions of the dorsal vagal complex to inhibit emesis in the ferret. Am J Physiol Gastrointest Liver Physiol 285:G566–G576

    PubMed  Google Scholar 

  • Vigano D, Cascio MG, Rubino T, Fezza F, Vaccani A, Di Marzo V, Parolaro D (2003) Chronic morphine modulates the contents of the endocannabinoid, 2-arachidonoyl glycerol, in rat brain. Neuropsychopharmacology 28:1160–1167

    PubMed  CAS  Google Scholar 

  • Yiangou Y, Facer P, Dyer NHC, Chan CL H, Knowles C, Williams NS, Anand P (2001) Vanilloid receptor 1 immunoreactivity in inflamed human bowel. Lancet 357:1338–1339

    CrossRef  PubMed  CAS  Google Scholar 

  • Zygmunt PM, Petersson J, Andersson DA, Chuang HH, Sorgard M, Di Marzo V, Julius D, Hogestatt ED (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400:452–457

    PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. A. A. Coutts

    Present address: School of Medical Sciences, College of Life Sciences and Medicine, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD, UK

Authors and Affiliations

  1. Department of Experimental Pharmacology, University of Naples Federico II, via D Montesano 49, 80131, Naples, Italy

    A. A. Izzo

Authors
  1. A. A. Izzo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. A. Coutts
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. School of Medical Sciences, Institute of Medical Science, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, Scotland, UK

    Professor Dr. Roger G. Pertwee

Rights and permissions

Reprints and Permissions

Copyright information

© 2005 Springer-Verlag

About this chapter

Cite this chapter

Izzo, A.A., Coutts, A.A. (2005). Cannabinoids and the Digestive Tract. In: Pertwee, R.G. (eds) Cannabinoids. Handbook of Experimental Pharmacology, vol 168. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-26573-2_19

Download citation

search

Navigation