Cannabidiol, a safe and non-psychotropic ingredient of the marijuana plant Cannabis sativa, is protective in a murine model of colitis.
Inflammatory bowel disease affects millions of individuals; nevertheless, pharmacological treatment is disappointingly unsatisfactory. Cannabidiol, a safe and non-psychotropic ingredient of marijuana, exerts pharmacological effects (e.g., antioxidant) and mechanisms (e.g., inhibition of endocannabinoids enzymatic degradation) potentially beneficial for the inflamed gut. Thus, we investigated the effect of cannabidiol in a murine model of colitis. Colitis was induced in mice by intracolonic administration of dinitrobenzene sulfonic acid. Inflammation was assessed both macroscopically and histologically. In the inflamed colon, cyclooxygenase-2 and inducible nitric oxide synthase (iNOS) were evaluated by Western blot, interleukin-1beta and interleukin-10 by ELISA, and endocannabinoids by isotope dilution liquid chromatography-mass spectrometry. Human colon adenocarcinoma (Caco-2) cells were used to evaluate the effect of cannabidiol on oxidative stress. Cannabidiol reduced colon injury, inducible iNOS (but not cyclooxygenase-2) expression, and interleukin-1beta, interleukin-10, and endocannabinoid changes associated with 2,4,6-dinitrobenzene sulfonic acid administration. In Caco-2 cells, cannabidiol reduced reactive oxygen species production and lipid peroxidation. In conclusion, cannabidiol, a likely safe compound, prevents experimental colitis in mice.
Borrelli
Francesca
F
Department of Experimental Pharmacology, University of Naples Federico II, via D Montesano 49, 80131 Naples, Italy.
Aviello
Gabriella
G
Romano
Barbara
B
Orlando
Pierangelo
P
Capasso
Raffaele
R
Maiello
Francesco
F
Guadagno
Federico
F
Petrosino
Stefania
S
Capasso
Francesco
F
Di Marzo
Vincenzo
V
Izzo
Angelo A
AA
D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D018938:Caco-2 Cells; D002185:Cannabidiol / Q000494:pharmacology / Q000627:therapeutic use*; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism; D002188:Cannabis / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D003092:Colitis / Q000517:prevention & control*; D003106:Colon / Q000187:drug effects / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D000099252:Fatty Acid Amide Hydrolases
D000581:Amidohydrolases; D000975:Antioxidants; D002185:Cannabidiol; D063385:Cannabinoid Receptor Modulators; D051546:Cyclooxygenase 2; D016753:Interleukin-10; D053583:Interleukin-1beta; D052247:Nitric Oxide Synthase Type II; D000099252:Fatty Acid Amide Hydrolases
Pharmacology. 1980;21(3):175-85
7413719
Gastroenterology. 2002 Dec;123(6):2140-4
12454869
Br J Pharmacol. 2000 Aug;130(8):1949-59
10952687
Br J Pharmacol. 2008 Jan;153(2):199-215
17828291
Br J Pharmacol. 2007 Aug;151(8):1272-9
17592514
Nature. 2007 Jul 26;448(7152):427-34
17653185
Biochem Pharmacol. 2002 Jul 1;64(1):1-8
12106600
Gut. 2006 Oct;55(10):1373-6
16966693
J Pharmacol Exp Ther. 2006 Sep;318(3):1375-87
16728591
Am J Pathol. 2006 Jan;168(1):235-44
16400026
FASEB J. 2006 Mar;20(3):568-70
16403786
Inflammopharmacology. 2007 Oct;15(5):188-95
17943250
Br J Pharmacol. 2008 Mar;153(6):1272-80
18223666
Methods Enzymol. 1990;186:407-21
2233308
Am J Physiol Gastrointest Liver Physiol. 2006 Aug;291(2):G364-71
16574988
Gastroenterology. 1998 Aug;115(2):297-306
9679035
Gastroenterology. 2006 Mar;130(3):940-87
16530532
Br J Pharmacol. 2008 Jul;154(5):1001-8
18469842
J Mol Med (Berl). 2008 Jan;86(1):89-98
17823781
Gastroenterology. 2005 Sep;129(3):941-51
16143133
J Mol Med (Berl). 2006 Mar;84(3):253-8
16389547
J Neurochem. 2008 Feb;104(4):1091-100
18028339
Nat Prod Rep. 1999 Apr;16(2):131-43
10331283
Gut. 2000 Mar;46(3):344-9
10673295
J Clin Invest. 1996 Nov 1;98(9):2076-85
8903327
Chem Biodivers. 2007 Aug;4(8):1678-92
17712814
J Immunol Methods. 1983 Dec 16;65(1-2):55-63
6606682
J Clin Invest. 2004 Apr;113(8):1202-9
15085199
Nat Rev Drug Discov. 2008 May;7(5):438-55
18446159
Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H610-9
17384130
Biosci Biotechnol Biochem. 2006 Jun;70(6):1317-24
16794309
Gut. 2008 Apr;57(4):429-33
18079284
ScientificWorldJournal. 2006 May 25;6:577-88
16752007
Br J Pharmacol. 2008 Jan;153(2):263-70
17906675
Br J Pharmacol. 2007 Nov;152(5):583-93
17641667
Cancer Res. 1991 Jan 1;51(1):77-81
1988109
Proc Natl Acad Sci U S A. 1998 Jul 7;95(14):8268-73
9653176
J Mol Med (Berl). 2008 Aug;86(8):925-36
18493729
Gut. 2008 Aug;57(8):1140-55
18397936
Neurogastroenterol Motil. 2008 Aug;20(8):919-27
18373655
Immunology. 2004 Dec;113(4):427-37
15554920
Aliment Pharmacol Ther. 2002 Dec;16(12):1997-2015
12452933
Gastroenterology. 1992 Jul;103(1):65-71
1535326
World J Gastroenterol. 2008 Jan 21;14(3):354-77
18200659
Eur J Pharmacol. 2007 Feb 5;556(1-3):75-83
17157290
Br J Pharmacol. 2001 Oct;134(4):845-52
11606325