title: Cannabinoids alleviate experimentally induced intestinal inflammation by acting at central and peripheral receptors.
abstract: OBJECTIVE
  In an attempt to further investigate the role of cannabinoid (CB) system in the pathogenesis of inflammatory bowel diseases, we employed two recently developed ligands, AM841 (a covalently acting CB agonist) and CB13 (a peripherally-restricted CB agonist) to establish whether central and peripheral CB sites are involved in the anti-inflammatory action in the intestine.
  
  
  RESULTS
  AM841 (0.01, 0.1 and 1 mg/kg, i.p.) significantly decreased inflammation scores in dextran sulfate sodium (DSS)- and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-treated mice when administered before induction of colitis or as a treatment of existing intestinal inflammation. The effect was absent in CB1, CB2 and CB(1/2)-deficient mice. A peripherally-restricted agonist CB13 did not alleviate colitis when given i.p. (0.1 mg/kg), but significantly decreased inflammation score after central administration (0.1 µg/animal).
  
  
  CONCLUSIONS
  This is the first evidence that central and peripheral CB receptors are responsible for the protective and therapeutic action of cannabinoids in mouse models of colitis. Our observations provide new insight to CB pharmacology and validate the use of novel ligands AM841 and CB13 as potent tools in CB-related research.
authors.affiliation: Snyder Institute for Chronic Disease, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Biochemistry, Medical University of Lodz, Lodz, Poland.
authors.forename: Jakub
authors.initials: J
authors.lastname: Fichna
authors.affiliation: Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Misha
authors.initials: M
authors.lastname: Bawa
authors.affiliation: Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, United States of America.
authors.forename: Ganesh A
authors.initials: GA
authors.lastname: Thakur
authors.affiliation: Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, United States of America.
authors.forename: Ritesh
authors.initials: R
authors.lastname: Tichkule
authors.affiliation: Center for Drug Discovery, Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts, United States of America.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Makriyannis
authors.affiliation: Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Donna-Marie
authors.initials: DM
authors.lastname: McCafferty
authors.affiliation: Snyder Institute for Chronic Disease, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Sharkey
authors.affiliation: Snyder Institute for Chronic Disease, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; Division of Gastroenterology, Department of Medicine, University of Munich, Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Storr
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000494:pharmacology*; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D010587:Phagocytosis / Q000187:drug effects; D043882:Receptors, Cannabinoid / Q000187:drug effects*
chemical_list: C507046:7'-Isothiocyanato-11-hydroxy-1',1'-dimethylheptylhexahydrocannabinol; D002186:Cannabinoids; D043882:Receptors, Cannabinoid; D013759:Dronabinol