Z Gastroenterol 2006; 44(2): 185-191
DOI: 10.1055/s-2005-858931
Übersicht

© Karl Demeter Verlag im Georg Thieme Verlag KG Stuttgart · New York

Perspektiven von Cannabinoiden in der Gastroenterologie

Perspectives of Cannabinoids in GastroenterologyM. Storr1 , B. Yüce1 , B. Göke1
  • 1Medizinische Klinik und Poliklinik II der Ludwig-Maximilians-Universität München
Further Information

Publication History

Manuskript eingetroffen: 2.9.2005

Manuskript akzeptiert: 13.11.2005

Publication Date:
03 February 2006 (online)

Zusammenfassung

Frühere Kulturen verwandten Extrakte der Pflanze Cannabis sativa unter medizinischen Gesichtspunkten, unter anderem zur Behandlung von gastrointestinalen Symptomen wie Übelkeit, Erbrechen, Diarrhö und abdominellen Schmerzen. Bis ca. 1920 war Cannabisextrakt ein häufig verwendetes Therapeutikum, z. B. bei Diarrhöerkrankungen in den Vereinigten Staaten. Die missbräuchliche Verwendung von Cannabinoiden als Sucht- und Rauschmittel führten zu einem weltweiten gesetzlichen Verbot und damit zum vorläufigen Ende von Cannabisextrakten als Heilmittel. Die Charakterisierung eines endogenen Cannabinoidsystems, bestehend aus endogenen Rezeptoren, Agonisten, Antagonisten und degradierenden Enzymen, öffnet die Tür für ein Comeback der Cannabinoide in die Medizin. Insbesondere den klinisch gut belegten Effekten in der Behandlung von Schmerzen verschiedenster Art, Kachexie im Rahmen von HIV oder Tumorerkrankungen sowie Übelkeit und Erbrechen im Rahmen von Chemotherapien ist es zu verdanken, dass Patienten mit Cannabinoiden wirksame Medikamente verabreicht werden können. In dieser Übersicht werden mit Übelkeit und Erbrechen diejenigen Indikationen diskutiert, in denen Cannabinoide zur Behandlung von Funktionsstörungen des Gastrointestinaltraktes aktuell eingesetzt werden. Weiterhin werden diejenigen Indikationen vorgestellt, bei denen tierexperimentelle Daten und Einzelbeobachtungen am Menschen einen zukünftigen Einsatz denkbar erscheinen lassen.

Abstract

In early cultures, extracts of the plant Cannabis sativa were medically used for the treatment of gastrointestinal symptoms like nausea, vomiting, diarrhoea and abdominal pain. In the United States cannabis extracts were frequently used as drugs, e. g., for the treatment of diarrhoea, until around 1920. The possibility of cannabis abuse resulted in a worldwide prohibition and thus the temporary ending of the medical use of cannabinoids. The characterisation of an endogenous cannabinoid system consisting of receptors, endogenous agonists, antagonists and degrading enzymes opens the door for a comeback of cannabinoids in medicine. The clinically proven effects in the treatment of pain, cachexia in conjunction with HIV, or malignant disease and treatment of nausea and vomiting in conjunction with chemotherapy now result in the prescription of cannabinoids as valuable medication. This review will discuss the value of cannabinoids in the treatment of nausea and vomiting, i. e., the indications for which cannabinoids are presently used in gastroenterology. Additionally, this review will discuss potential indications within gastroenterology, where results from basic research or individual observations suggest that a future use of cannabinoids in gastroenterology seems possible.

Literatur

  • 1 Grinspoon L. The future of medical marijuana.  Forsch Komplementarmed. 1999;  44 40-43
  • 2 Mechoulam R, Gaoni Y. The absolute configuration of delta-1-tetrahydrocannabinol, the major active constituent of hashish.  Tetrahedron Lett. 1967;  44 1109-1111
  • 3 Matsuda L A, Lolait S J, Brownstein M J. et al . Structure of a cannabinoid receptor and functional expression of the cloned cDNA.  Nature. 1990;  44 561-564
  • 4 Howlett A C, Barth F, Bonner T I. et al . International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors.  Pharmacol Rev. 2002;  44 161-202
  • 5 Wright K, Rooney N, Feeney M. et al . Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing.  Gastroenterology. 2005;  44 437-453
  • 6 Pertwee R G. Pharmacology of cannabinoid CB1 and CB2 receptors.  Pharmacol Ther. 1997;  44 129-180
  • 7 Pertwee R G. Cannabinoids and the gastrointestinal tract.  Gut. 2001;  44 859-867
  • 8 Izzo A A, Mascolo N, Capasso F. The gastrointestinal pharmacology of cannabinoids.  Curr Opin Pharmacol. 2001;  44 597-603
  • 9 Massa F, Storr M, Lutz B. The endocannabinoidsystem in the physiology and pathophysiology of the gastrointestinal tract.  Mol Med. 2005; in press; 
  • 10 Van Gaal L F, Rissanen A M, Scheen A J. et al . Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study.  Lancet. 2005;  44 1389-1397
  • 11 Tramer M R, Carroll D, Campbell F A. et al . Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review.  BMJ. 2001;  44 16-21
  • 12 Walsh D, Nelson K A, Mahmoud F A. Established and potential therapeutic applications of cannabinoids in oncology.  Support Care Cancer. 2003;  44 137-143
  • 13 Coutts A A, Izzo A A. The gastrointestinal pharmacology of cannabinoids: an update.  Current Opinion in Pharmacology. 2004;  44 572-579
  • 14 Inui A. Emesis, appetite, and endocannabinoids.  Gastroenterology. 2002;  44 655-656
  • 15 Darmani N A, Johnson J C. Central and peripheral mechanisms contribute to the antiemetic actions of delta-9-tetrahydrocannabinol against 5-hydroxytryptophan-induced emesis.  European Journal of Pharmacology. 2004;  44 201-212
  • 16 Van Sickle M D, Oland L D, Mackie K. et al . Distribution of the cannabinoid 1 receptor in the brainstem and gut: A novel neuroregulatory system in emesis.  Gastroenterology. 2001;  44 A197
  • 17 Annese V, Bassotti G, Napolitano G. et al . Gastrointestinal motility disorders in patients with inactive Crohn’s disease.  Scand J Gastroenterol. 1997;  44 1107-1117
  • 18 Pinto L, Capasso R, Di Carlo G. et al . Endocannabinoids and the gut.  Prostaglandins Leukotrienes and Essential Fatty Acids. 2002;  44 333-341
  • 19 Massa F, Marsicano G, Hermann H. et al . The endogenous cannabinoid system protects against colonic inflammation.  J Clin Invest. 2004;  44 1202-1209
  • 20 Izzo A A, Fezza F, Capasso R. et al . Cannabinoid CB1-receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation.  British Journal of Pharmacology. 2001;  44 563-570
  • 21 Coutts A A, Pertwee R G. Inhibition by cannabinoid receptor agonists of acetylcholine release from the guinea-pig myenteric plexus.  Br J Pharmacol. 1997;  44 1557-1566
  • 22 Storr M, Gaffal E, Saur D. et al . Influence of cannabinoids on neurotransmission in rat gastric fundus.  Can J Physiol Pharmacol. 2002;  44 67-76
  • 23 Colombo G, Agabio R, Lobina C. et al . Cannabinoid modulation of intestional propulsion in mice.  Eur J Pharmacol. 1998;  44 67-69
  • 24 Heinemann A, Shahbazian A, Holzer P. Cannabinoid inhibition of guinea-pig intestinal peristalsis via inhibition of excitatory and activation of inhibitory neural pathways.  Neuropharmacology. 1999;  44 1289-1297
  • 25 Izzo A A, Mascolo N, Capasso R. et al . Inhibitory effect of cannabinoid agonists on gastric emptying in the rat.  Naunyn Schmiedebergs Arch Pharmacol. 1999;  44 221-223
  • 26 Pinto L, Izzo A A, Cascio M G. et al . Endocannabinoids as physiological regulators of colonic propulsion in mice.  Gastroenterology. 2002;  44 227-234
  • 27 Izzo A A, Mascolo N, Tonini M. et al . Modulation of peristalsis by cannabinoid CB(1) ligands in the isolated guinea-pig ileum.  Br J Pharmacol. 2000;  44 984-990
  • 28 Grinspoon L, Bakalar J B. Marihuana as medicine. A plea for reconsideration.  JAMA. 1995;  44 1875-1876
  • 29 Izzo A A, Pinto L, Borrelli F. et al . Central and peripheral cannabinoid modulation of gastrointestinal transit in physiological states or during the diarrhoea induced by croton oil.  Br J Pharmacol. 2000;  44 1627-1632
  • 30 Izzo A A, Capasso F, Costagliola A. et al . An endogenous cannabinoid tone attenuates cholera toxin-induced fluid accumulation in mice.  Gastroenterology. 2003;  44 765-774
  • 31 Tyler K, Hillard C J, Van Greenwood-Meerveld B. Inhibition of small intestinal secretion by cannabinoids is CB1 receptor-mediated in rats.  European Journal of Pharmacology. 2000;  44 207-211
  • 32 Drossman D A, Whitehead W E, Camilleri M. Irritable bowel syndrome: a technical review for practice guideline development.  Gastroenterology. 1997;  44 2120-2137
  • 33 Hornby P J, Prouty S M. Involvement of cannabinoid receptors in gut motility and visceral perception.  Br J Pharmacol. 2004;  44 1335-1345
  • 34 Hunt R H, Tougas G. Evolving concepts in functional gastrointestinal disorders: promising directions for novel pharmaceutical treatments.  Best Pract Res Clin Gastroenterol. 2002;  44 869-883
  • 35 Tognetto M, Amadesi S, Harrison S. et al . Anandamide excites central terminals of dorsal root ganglion neurons via vanilloid receptor-1 activation.  J Neurosci. 2001;  44 1104-1109
  • 36 Madl C, Druml W. Gastrointestinal disorders of the critically ill. Systemic consequences of ileus.  Best Pract Res Clin Gastroenterol. 2003;  44 445-456
  • 37 Mascolo N, Izzo A A, Ligresti A. et al . The endocannabinoid system and the molecular basis of paralytic ileus in mice.  FASEB J. 2002;  44 1973-1975
  • 38 Ligresti A, Bisogno T, Matias I. et al . Possible endocannabinoid control of colorectal cancer growth.  Gastroenterology. 2003;  44 677-687
  • 39 Patsos H A, Hicks D J, Greenhough A. et al . Cannabinoids and cancer: potential for colorectal cancer therapy.  Biochem Soc Trans. 2005;  44 712-714
  • 40 Holloway R, Penagini R, Ireland A. Criteria for objective definition of transient lower esophageal sphincter relaxation.  Am J Physiol. 1995;  44 G128-G133
  • 41 Lehmann A, Blackshaw L A, Branden L. et al . Cannabinoid receptor agonism inhibits transient lower esophageal sphincter relaxations and reflux in dogs.  Gastroenterology. 2002;  44 1129-1134
  • 42 Partosoedarso E R, Abrahams T P, Scullion R T. et al . Cannabinoid1 receptor in the dorsal vagal complex modulates lower oesophageal sphincter relaxation in ferrets.  Journal of Physiology-London. 2003;  44 149-158
  • 43 Sofia R D, Diamantis W, Harrison J E. et al . Evaluation of antiulcer activity of delta9-tetrahydrocannabinol in the Shay rat test.  Pharmacology. 1978;  44 173-177
  • 44 Adami M, Frati P, Bertini S. et al . Gastric antisecretory role and immunohistochemical localization of cannabinoid receptors in the rat stomach.  British Journal of Pharmacology. 2002;  44 1598-1606
  • 45 Coruzzi G, Adami M, Coppelli G. et al . Inhibitory effect of the cannabinoid receptor agonist WIN 55,212 - 2 on pentagastrin-induced gastric acid secretion in the anaesthetized rat.  Naunyn-Schmiedebergs Archives of Pharmacology. 1999;  44 715-718
  • 46 Nalin D R, Levine M M, Rhead J. et al . Cannabis, Hypochlorhydria, and Cholera.  Lancet. 1978;  44 859-862
  • 47 Germano M P, D’Angelo V, Mondello M R. et al . Cannabinoid CB1-mediated inhibition of stress-induced gastric ulcers in rats.  Naunyn Schmiedebergs Arch Pharmacol. 2001;  44 241-244

PD Dr. Martin Storr

Medizinische Klinik und Poliklinik II der Ludwig-Maximilians-Universität München

Marchioninistr. 15

81377 München

Phone: ++ 49/89/7 09 50

Fax: ++ 49/89/70 95 52 81

Email: martin.storr@med.uni-muenchen.de

    >