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Review

Cannabinoids as Novel Anti-Inflammatory Drugs

Prakash NagarkattiDepartment of Pathology, Microbiology and Immunology, University of South Carolina, School of Medicine Columbia, SC29208, USACorrespondence[email protected]
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,
Rupal PandeyDepartment of Pathology, Microbiology and Immunology, University of South Carolina, School of Medicine Columbia, SC29208, USAView further author information
,
Sadiye Amcaoglu RiederDepartment of Pathology, Microbiology and Immunology, University of South Carolina, School of Medicine Columbia, SC29208, USAView further author information
,
Venkatesh L HegdeDepartment of Pathology, Microbiology and Immunology, University of South Carolina, School of Medicine Columbia, SC29208, USAView further author information
&
Mitzi NagarkattiDepartment of Pathology, Microbiology and Immunology, University of South Carolina, School of Medicine Columbia, SC29208, USAView further author information
Pages 1333-1349 | Published online: 21 Oct 2009

Bibliography

  • Guzman M . Cannabinoids: potential anticancer agents.Nat. Rev. Cancer3, 745–755 (2003).
  • Inui A . Cancer anorexia-cachexia syndrome: current issues in research and management.CA Cancer J. Clin.52, 72–91 (2002).
  • Pollmann W , FenebergW. Current management of pain associated with multiple sclerosis.CNS Drugs22, 291–324 (2008).
  • Tramer MR , CarrollD, CampbellFA, ReynoldsDJ, MooreRA, McQuayHJ. Cannabinoids for control of chemotherapy induced nausea and vomiting: quantitative systematic review.BMJ323, 16–21 (2001).
  • Croxford JL , YamamuraT. Cannabinoids and the immune system: potential for the treatment of inflammatory diseases?J. Neuroimmunol.166, 3–18 (2005).
  • Mackie K . Cannabinoid receptors as therapeutic targets.Annu. Rev. Pharmacol. Toxicol.46, 101–122 (2006).
  • Stefano GB , LiuY, GoligorskyMS. Cannabinoid receptors are coupled to nitric oxide release in invertebrate immunocytes, microglia, and human monocytes.J. Biol. Chem.271, 19238–19242 (1996).
  • Devane WA , HanusL, BreuerAet al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258, 1946–1949 (1992).
  • Mechoulam R , Ben-ShabatS, HanusLet al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol. 50, 83–90 (1995).
  • Sugiura T , KondoS, SukagawaAet al. 2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain. Biochem. Biophys. Res. Commun. 215, 89–97 (1995).
  • Cravatt BF , GiangDK, MayfieldSP, BogerDL, LernerRA, GilulaNB. Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides.Nature384, 83–87 (1996).
  • Kaczocha M , GlaserST, DeutschDG. Identification of intracellular carriers for the endocannabinoid anandamide.Proc. Natl Acad. Sci. USA106, 6375–6380 (2009).
  • Rodriguez de Fonseca F , Del Arco I, Bermudez-Silva FJ, Bilbao A, Cippitelli A, Navarro M. The endocannabinoid system: physiology and pharmacology. Alcohol Alcoholism40, 2–14 (2005).
  • Hengartner MO . The biochemistry of apoptosis.Nature407, 770–776 (2000).
  • Igney FH , KrammerPH. Death and anti-death: tumour resistance to apoptosis.Nat. Rev. Cancer2, 277–288 (2002).
  • Zhu W , FriedmanH, KleinTW. Δ9-tetrahydrocannabinol induces apoptosis in macrophages and lymphocytes: involvement of Bcl-2 and caspase-1.J. Pharmacol. Exp. Ther.286, 1103–1109 (1998).
  • McKallip RJ , LombardC, MartinBR, NagarkattiM, NagarkattiPS. D(9)-tetrahydrocannabinol-induced apoptosis in the thymus and spleen as a mechanism of immunosuppression in vitro and in vivo. J. Pharmacol. Exp. Ther.302, 451–465 (2002).
  • Do Y , McKallipRJ, NagarkattiM, NagarkattiPS. Activation through cannabinoid receptors 1 and 2 on dendritic cells triggers NF-κB-dependent apoptosis: novel role for endogenous and exogenous cannabinoids in immunoregulation.J. Immunol.173, 2373–2382 (2004).
  • Lu T , NewtonC, PerkinsI, FriedmanH, KleinTW. Cannabinoid treatment suppresses the T-helper cell-polarizing function of mouse dendritic cells stimulated with Legionella pneumophila infection. J. Pharmacol. Exp. Ther.319, 269–276 (2006).
  • Lee CY , WeySP, LiaoMHet al. A comparative study on cannabidiol-induced apoptosis in murine thymocytes and EL-4 thymoma cells. Int. Immunopharmacol. 8, 732–740 (2008).
  • Bidinger B , TorresR, RossettiRGet al. Ajulemic acid, a nonpsychoactive cannabinoid acid, induces apoptosis in human T lymphocytes. Clin. Immunol. 108, 95–102 (2003).
  • Lombard C , NagarkattiM, NagarkattiP. CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: potential role for CB2-selective ligands as immunosuppressive agents.Clin. Immunol.122, 259–270 (2007).
  • Molina-Holgado F , Molina-HolgadoE, GuazaC, RothwellNJ. Role of CB1 and CB2 receptors in the inhibitory effects of cannabinoids on lipopolysaccharide-induced nitric oxide release in astrocyte cultures.J. Neurosci. Res.67, 829–836 (2002).
  • Croxford JL , PryceG, JacksonSJet al. Cannabinoid-mediated neuroprotection, not immunosuppression, may be more relevant to multiple sclerosis. J. Neuroimmunol. 193, 120–129 (2008).
  • Klein TW , NewtonCA, NakachiN, FriedmanH. Δ9-tetrahydrocannabinol treatment suppresses immunity and early IFN-γ, IL-12, and IL-12 receptor β 2 responses to Legionella pneumophila infection. J. Immunol.164, 6461–6466 (2000).
  • Srivastava MD , SrivastavaBI, BrouhardB. Δ9 tetrahydrocannabinol and cannabidiol alter cytokine production by human immune cells.Immunopharmacology40, 179–185 (1998).
  • Derocq JM , JbiloO, BouaboulaM, SeguiM, ClereC, CasellasP. Genomic and functional changes induced by the activation of the peripheral cannabinoid receptor CB2 in the promyelocytic cells HL-60. Possible involvement of the CB2 receptor in cell differentiation.J. Biol. Chem.275, 15621–15628 (2000).
  • Puffenbarger RA , BootheAC, CabralGA. Cannabinoids inhibit LPS-inducible cytokine mRNA expression in rat microglial cells.Glia29, 58–69 (2000).
  • Smith SR , TerminelliC, DenhardtG. Effects of cannabinoid receptor agonist and antagonist ligands on production of inflammatory cytokines and anti-inflammatory interleukin-10 in endotoxemic mice.J. Pharmacol. Exp. Ther.293, 136–150 (2000).
  • Smolen JS , MainiRN. Interleukin-6: a new therapeutic target.Arthritis Res. Ther.8(Suppl. 2), S5 (2006).
  • Zurier RB , RossettiRG, LaneJH, GoldbergJM, HunterSA, BursteinSH. Dimethylheptyl-THC-11 oic acid: a nonpsychoactive antiinflammatory agent with a cannabinoid template structure.Arthritis Rheum.41, 163–170 (1998).
  • Parker J , AtezF, RossettiRG, SkulasA, PatelR, ZurierRB. Suppression of human macrophage interleukin-6 by a nonpsychoactive cannabinoid acid.Rheumatol. Int.28, 631–635 (2008).
  • Rajesh M , PanH, MukhopadhyayPet al. Cannabinoid-2 receptor agonist HU-308 protects against hepatic ischemia/reperfusion injury by attenuating oxidative stress, inflammatory response, and apoptosis. J. Leukoc. Biol. 82, 1382–1389 (2007).
  • Selvi E , LorenziniS, Garcia-GonzalezEet al. Inhibitory effect of synthetic cannabinoids on cytokine production in rheumatoid fibroblast-like synoviocytes. Clin. Exp. Rheumatol. 26, 574–581 (2008).
  • Valk P , VerbakelS, VankanYet al. Anandamide, a natural ligand for the peripheral cannabinoid receptor is a novel synergistic growth factor for hematopoietic cells. Blood 90, 1448–1457 (1997).
  • Rockwell CE , SniderNT, ThompsonJT, Vanden Heuvel JP, Kaminski NE. Interleukin-2 suppression by 2-arachidonyl glycerol is mediated through peroxisome proliferator-activated receptor γ independently of cannabinoid receptors 1 and 2. Mol. Pharmacol.70, 101–111 (2006).
  • Kishimoto S , KobayashiY, OkaS, GokohM, WakuK, SugiuraT. 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces accelerated production of chemokines in HL-60 cells.J. Biochem.135, 517–524 (2004).
  • Mestre L , CorreaF, Arevalo-MartinAet al. Pharmacological modulation of the endocannabinoid system in a viral model of multiple sclerosis. J. Neurochem. 92, 1327–1339 (2005).
  • Maccarrone M , ValensiseH, BariM, LazzarinN, RomaniniC, Finazzi-AgroA. Progesterone up-regulates anandamide hydrolase in human lymphocytes: role of cytokines and implications for fertility.J. Immunol.166, 7183–7189 (2001).
  • Fischer-Stenger K , Dove Pettit DA, Cabral GA. Δ9-tetrahydrocannabinol inhibition of tumor necrosis factor-α: suppression of post-translational events. J. Pharmacol. Exp. Ther.267, 1558–1565 (1993).
  • Zhu W , NewtonC, DkaY, FriedmanH, KleinTW. Δ9-tetrahydrocannabinol enhances the secretion of interleukin 1 from endotoxin-stimulated macrophages.J. Pharmacol. Exp. Ther.270, 1334–1339 (1994).
  • Weiner HL . The challenge of multiple sclerosis: how do we cure a chronic heterogeneous disease?Ann. Neurol.65, 239–248 (2009).
  • Pertwee RG . Cannabinoids and multiple sclerosis.Pharmacol. Ther.95, 165–174 (2002).
  • Arevalo-Martin A , Garcia-OvejeroD, GomezOet al. CB2 cannabinoid receptors as an emerging target for demyelinating diseases: from neuroimmune interactions to cell replacement strategies. Br. J. Pharmacol. 153, 216–225 (2008).
  • Centonze D , BariM, RossiSet al. The endocannabinoid system is dysregulated in multiple sclerosis and in experimental autoimmune encephalomyelitis. Brain 130, 2543–2553 (2007).
  • Ghosh S , PreetA, GroopmanJE, GanjuRK. Cannabinoid receptor CB2 modulates the CXCL12/CXCR4-mediated chemotaxis of T lymphocytes.Mol. Immunol.43, 2169–2179 (2006).
  • Iglesias A , BauerJ, LitzenburgerT, SchubartA, LiningtonC. T- and B-cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis.Glia36, 220–234 (2001).
  • Aranami T , YamamuraT. Th17 Cells and autoimmune encephalomyelitis (EAE/MS).Allergol. Int.57, 115–120 (2008).
  • Frisullo G , NocitiV, IorioRet al. IL17 and IFNγ production by peripheral blood mononuclear cells from clinically isolated syndrome to secondary progressive multiple sclerosis. Cytokine 44, 22–25 (2008).
  • Sanchez AJ , Gonzalez-PerezP, Galve-RoperhI, Garcia-MerinoA. R-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)-pyrrolo-[1,2,3-de]-1,4 -benzoxazin-6-yl]-1-naphtalenylmethanone (WIN-2) ameliorates experimental autoimmune encephalomyelitis and induces encephalitogenic T cell apoptosis: partial involvement of the CB(2) receptor. Biochem. Pharmacol.72, 1697–1706 (2006).
  • Arevalo-Martin A , VelaJM, Molina-HolgadoE, BorrellJ, GuazaC. Therapeutic action of cannabinoids in a murine model of multiple sclerosis.J. Neurosci.23, 2511–2516 (2003).
  • Mestre L , DocagneF, CorreaFet al. A cannabinoid agonist interferes with the progression of a chronic model of multiple sclerosis by downregulating adhesion molecules. Mol. Cell Neurosci. 40, 258–266 (2009).
  • Ehrhart J , ObregonD, MoriTet al. Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation. J. Neuroinflammation 2, 29 (2005).
  • Correa F , DocagneF, MestreLet al. A role for CB2 receptors in anandamide signalling pathways involved in the regulation of IL-12 and IL-23 in microglial cells. Biochem. Pharmacol. 77, 86–100 (2009).
  • Palazuelos J , DavoustN, JulienBet al. The CB(2) cannabinoid receptor controls myeloid progenitor trafficking: involvement in the pathogenesis of an animal model of multiple sclerosis. J. Biol. Chem. 283, 13320–13329 (2008).
  • Sheng WS , HuS, MinX, CabralGA, LokensgardJR, PetersonPK. Synthetic cannabinoid WIN55,212–212 inhibits generation of inflammatory mediators by IL-1β-stimulated human astrocytes.Glia49, 211–219 (2005).
  • Molina-Holgado F , Molina-HolgadoE, GuazaC. The endogenous cannabinoid anandamide potentiates interleukin-6 production by astrocytes infected with Theiler’s murine encephalomyelitis virus by a receptor-mediated pathway.FEBS Lett.433, 139–142 (1998).
  • Wood JD , AlpersDH, AndrewsPL. Fundamentals of neurogastroenterology.Gut45(Suppl. 2.), II6–II16 (1999).
  • Massa F , MarsicanoG, HermannHet al. The endogenous cannabinoid system protects against colonic inflammation. J. Clin. Invest. 113, 1202–1209 (2004).
  • Pertwee RG . Cannabinoids and the gastrointestinal tract.Gut48, 859–867 (2001).
  • Okayasu I , HatakeyamaS, YamadaM, OhkusaT, InagakiY, NakayaR. A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice.Gastroenterology98, 694–702 (1990).
  • Yamada Y , MarshallS, SpecianRD, GrishamMB. A comparative analysis of two models of colitis in rats.Gastroenterology102, 1524–1534 (1992).
  • Neurath MF , FussI, KelsallBL, StuberE, StroberW. Antibodies to interleukin 12 abrogate established experimental colitis in mice.J. Exp. Med.182, 1281–1290 (1995).
  • Kimball ES , SchneiderCR, WallaceNH, HornbyPJ. Agonists of cannabinoid receptor 1 and 2 inhibit experimental colitis induced by oil of mustard and by dextran sulfate sodium.Am. J. Physiol. Gastrointest. Liver Physiol.291, G364–G371 (2006).
  • Izzo AA , FezzaF, CapassoRet al. Cannabinoid CB1-receptor mediated regulation of gastrointestinal motility in mice in a model of intestinal inflammation. Br. J. Pharmacol. 134, 563–570 (2001).
  • Cravatt BF , DemarestK, PatricelliMPet al. Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase. Proc. Natl Acad. Sci. USA 98, 9371–9376 (2001).
  • Di Marzo V , De Petrocellis L, Fezza F, Ligresti A, Bisogno T. Anandamide receptors. Prostaglandins Leukot. Essent. Fatty Acids66, 377–391 (2002).
  • Biecker E , SagesserH, ReichenJ. Vasodilator mRNA levels are increased in the livers of portal hypertensive NO-synthase 3-deficient mice.Eur. J. Clin. Invest.34, 283–289 (2004).
  • Julien B , GrenardP, Teixeira-ClercFet al. Antifibrogenic role of the cannabinoid receptor CB2 in the liver. Gastroenterology 128, 742–755 (2005).
  • Osei-Hyiaman D , DePetrilloM, PacherPet al. Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J. Clin. Invest. 115, 1298–1305 (2005).
  • Schwabe RF , SiegmundSV. Potential role of CB2 receptors in cannabis smokers with chronic hepatitis C.Hepatology42, 975–977 (2005).
  • Teixeira-Clerc F , JulienB, GrenardPet al. CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. Nat. Med. 12, 671–676 (2006).
  • Batkai S , JaraiZ, WagnerJAet al. Endocannabinoids acting at vascular CB1 receptors mediate the vasodilated state in advanced liver cirrhosis. Nat. Med. 7, 827–832 (2001).
  • Batkai S , Osei-HyiamanD, PanHet al. Cannabinoid-2 receptor mediates protection against hepatic ischemia/reperfusion injury. FASEB J. 21, 1788–1800 (2007).
  • Gary-Bobo M , ElachouriG, GallasJFet al. Rimonabant reduces obesity-associated hepatic steatosis and features of metabolic syndrome in obese Zucker fa/fa rats. Hepatology 46, 122–129 (2007).
  • Siegmund SV , QianT, de Minicis S et al. The endocannabinoid 2-arachidonoyl glycerol induces death of hepatic stellate cells via mitochondrial reactive oxygen species. FASEB J.21, 2798–2806 (2007).
  • Hezode C , Roudot-ThoravalF, NguyenSet al. Daily cannabis smoking as a risk factor for progression of fibrosis in chronic hepatitis C. Hepatology 42, 63–71 (2005).
  • Avraham Y , IsraeliE, GabbayEet al. Endocannabinoids affect neurological and cognitive function in thioacetamide-induced hepatic encephalopathy in mice. Neurobiol. Dis. 21, 237–245 (2006).
  • Hegde VL , HegdeS, CravattBF, HofsethLJ, NagarkattiM, NagarkattiPS. Attenuation of experimental autoimmune hepatitis by exogenous and endogenous cannabinoids: involvement of regulatory T cells.Mol. Pharmacol.74, 20–33 (2008).
  • Hurlimann D , EnseleitF, RuschitzkaF. Rheumatoid arthritis, inflammation, and atherosclerosis.Herz29, 760–768 (2004).
  • Pratt AG , IsaacsJD, MatteyDL. Current concepts in the pathogenesis of early rheumatoid arthritis.Best Pract. Res. Clin. Rheumatol.23, 37–48 (2009).
  • Zurier RB , RossettiRG, BursteinSH, BidingerB. Suppression of human monocyte interleukin-1β production by ajulemic acid, a nonpsychoactive cannabinoid.Biochem. Pharmacol.65, 649–655 (2003).
  • George KL , SaltmanLH, SteinGS, LianJB, ZurierRB. Ajulemic acid, a nonpsychoactive cannabinoid acid, suppresses osteoclastogenesis in mononuclear precursor cells and induces apoptosis in mature osteoclast-like cells.J. Cell Physiol.214, 714–720 (2008).
  • Balkwill F , MantovaniA. Inflammation and cancer: back to Virchow?Lancet357, 539–545 (2001).
  • Malfait AM , GallilyR, SumariwallaPFet al. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc. Natl Acad. Sci. USA 97, 9561–9566 (2000).
  • Sumariwalla PF , GallilyR, TchilibonS, FrideE, MechoulamR, FeldmannM. A novel synthetic, nonpsychoactive cannabinoid acid (HU-320) with antiinflammatory properties in murine collagen-induced arthritis.Arthritis Rheum.50, 985–998 (2004).
  • Mamytbekova A , RezabekK, KacerovskaH, GrimovaJ, SvobodovaJ. Antimetastatic effect of flurbiprofen and other platelet aggregation inhibitors.Neoplasma33, 417–421 (1986).
  • Sarfaraz S , AdhamiVM, SyedDN, AfaqF, MukhtarH. Cannabinoids for cancer treatment: progress and promise.Cancer Res.68, 339–342 (2008).
  • Carracedo A , GironellaM, LorenteMet al. Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes. Cancer Res. 66, 6748–6755 (2006).
  • Casanova ML , BlazquezC, Martinez-PalacioJet al. Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. J. Clin. Invest. 111, 43–50 (2003).
  • Galve-Roperh I , SanchezC, CortesMLet al. Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nat. Med. 6, 313–319 (2000).
  • Sanchez C , de CeballosML, Gomez del PulgarTet al. Inhibition of glioma growth in vivo by selective activation of the CB(2) cannabinoid receptor. Cancer Res.61, 5784–5789 (2001).
  • Sarfaraz S , AfaqF, AdhamiVM, MukhtarH. Cannabinoid receptor as a novel target for the treatment of prostate cancer.Cancer Res.65, 1635–1641 (2005).
  • Velasco G , Galve-RoperhI, SanchezC, BlazquezC, GuzmanM. Hypothesis: cannabinoid therapy for the treatment of gliomas?Neuropharmacology47, 315–323 (2004).
  • Lombard C , NagarkattiM, NagarkattiPS. Targeting cannabinoid receptors to treat leukemia: role of cross-talk between extrinsic and intrinsic pathways in Δ9-tetrahydrocannabinol (THC)-induced apoptosis of Jurkat cells.Leuk. Res.29, 915–922 (2005).
  • Jia W , HegdeVL, SinghNPet al. Δ9-tetrahydrocannabinol-induced apoptosis in Jurkat leukemia T cells is regulated by translocation of Bad to mitochondria. Mol. Cancer Res. 4, 549–562 (2006).
  • McKallip RJ , LombardC, FisherMet al. Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease. Blood 100, 627–634 (2002).
  • Ligresti A , BisognoT, MatiasIet al. Possible endocannabinoid control of colorectal cancer growth. Gastroenterology 125, 677–687 (2003).
  • Cianchi F , PapucciL, SchiavoneNet al. Cannabinoid receptor activation induces apoptosis through tumor necrosis factor α-mediated ceramide de novo synthesis in colon cancer cells. Clin. Cancer Res. 14, 7691–7700 (2008).
  • Bifulco M , LaezzaC, ValentiMet al. A new strategy to block tumor growth by inhibiting endocannabinoid inactivation. FASEB J. 18, 1606–1608 (2004).
  • De Lago E , GustafssonSB, Fernandez-RuizJet al. Acyl-based anandamide uptake inhibitors cause rapid toxicity to C6 glioma cells at pharmacologically relevant concentrations. J. Neurochem. 99, 677–688 (2006).
  • Endsley MP , AggarwalN, IsbellMAet al. Diverse roles of 2-arachidonoylglycerol in invasion of prostate carcinoma cells: location, hydrolysis and 12-lipoxygenase metabolism. Int. J. Cancer 121, 984–991 (2007).
  • Nithipatikom K , EndsleyMP, IsbellMA, WheelockCE, HammockBD, CampbellWB. A new class of inhibitors of 2-arachidonoylglycerol hydrolysis and invasion of prostate cancer cells.Biochem. Biophys. Res. Commun.332, 1028–1033 (2005).
  • Contassot E , TenanM, SchnurigerV, PelteMF, DietrichPY. Arachidonyl ethanolamide induces apoptosis of uterine cervix cancer cells via aberrantly expressed vanilloid receptor-1.Gynecol. Oncol.93, 182–188 (2004).
  • Contassot E , WilmotteR, TenanMet al. Arachidonylethanolamide induces apoptosis of human glioma cells through vanilloid receptor-1. J. Neuropathol. Exp. Neurol. 63, 956–963 (2004).
  • DeMorrow S , GlaserS, FrancisHet al. Opposing actions of endocannabinoids on cholangiocarcinoma growth: recruitment of Fas and Fas ligand to lipid rafts. J. Biol. Chem. 282, 13098–13113 (2007).
  • Bifulco M , LaezzaC, PortellaGet al. Control by the endogenous cannabinoid system of ras oncogene-dependent tumor growth. FASEB J. 15, 2745–2747 (2001).
  • Caffarel MM , SarrioD, PalaciosJ, GuzmanM, SanchezC. Δ9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation.Cancer Res.66, 6615–6621 (2006).
  • Ek S , HogerkorpCM, DictorM, EhingerM, BorrebaeckCA. Mantle cell lymphomas express a distinct genetic signature affecting lymphocyte trafficking and growth regulation as compared with subpopulations of normal human B cells.Cancer Res.62, 4398–4405 (2002).
  • Islam TC , AsplundAC, LindvallJMet al. High level of cannabinoid receptor 1, absence of regulator of G protein signalling 13 and differential expression of cyclin D1 in mantle cell lymphoma. Leukemia 17, 1880–1890 (2003).
  • Wills-Karp M . Immunologic basis of antigen-induced airway hyperresponsiveness.Annu. Rev. Immunol.17, 255–281 (1999).
  • Anderson GP , CoyleAJ. TH2 and ‘TH2-like’ cells in allergy and asthma: pharmacological perspectives.Trends Pharmacol. Sci.15, 324–332 (1994).
  • Jan TR , FarrajAK, HarkemaJR, KaminskiNE. Attenuation of the ovalbumin-induced allergic airway response by cannabinoid treatment in A/J mice.Toxicol. Appl. Pharmacol.188, 24–35 (2003).
  • Tashkin DP , ReissS, ShapiroBJ, CalvareseB, OlsenJL, LodgeJW. Bronchial effects of aerosolized Δ9-tetrahydrocannabinol in healthy and asthmatic subjects.Am. Rev. Respir. Dis.115, 57–65 (1977).
  • Abboud RT , SandersHD. Effect of oral administration of D-tetrahydrocannabinol on airway mechanics in normal and asthmatic subjects.Chest70, 480–485 (1976).
  • Hartley JP , NogradySG, SeatonA. Bronchodilator effect of D1-tetrahydrocannabinol.Br. J. Clin. Pharmacol.5, 523–525 (1978).
  • Calignano A , KatonaI, DesarnaudFet al. Bidirectional control of airway responsiveness by endogenous cannabinoids. Nature 408, 96–101 (2000).
  • Rajesh M , MukhopadhyayP, BatkaiSet al. Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption. Am. J. Physiol. Heart Circ. Physiol. 293, H610–H619 (2007).
  • Rajesh M , MukhopadhyayP, HaskoG, HuffmanJW, MackieK, PacherP. CB2 cannabinoid receptor agonists attenuate TNF-α-induced human vascular smooth muscle cell proliferation and migration.Br. J. Pharmacol.153, 347–357 (2008).
  • de Kozak Y , SakaiJ, ThillayeB, FaureJP. S antigen-induced experimental autoimmune uveo-retinitis in rats.Curr. Eye Res.1, 327–337 (1981).
  • Xu H , ChengCL, ChenMet al. Anti-inflammatory property of the cannabinoid receptor-2-selective agonist JWH-133 in a rodent model of autoimmune uveoretinitis. J. Leukoc. Biol. 82, 532–541 (2007).
  • Correa F , MestreL, DocagneF, GuazaC. Activation of cannabinoid CB2 receptor negatively regulates IL-12p40 production in murine macrophages: role of IL-10 and ERK1/2 kinase signaling.Br. J. Pharmacol.145, 441–448 (2005).
  • Broderick CA , SmithAJ, BalagganKSet al. Local administration of an adeno-associated viral vector expressing IL-10 reduces monocyte infiltration and subsequent photoreceptor damage during experimental autoimmune uveitis. Mol. Ther. 12, 369–373 (2005).
  • De Kozak Y , Thillaye-GoldenbergB, NaudMC, Da Costa AV, Auriault C, Verwaerde C. Inhibition of experimental autoimmune uveoretinitis by systemic and subconjunctival adenovirus-mediated transfer of the viral IL-10 gene. Clin. Exp. Immunol.130, 212–223 (2002).
  • Mandrup-Poulsen T . β Cell death and protection.Ann. NY Acad. Sci.1005, 32–42 (2003).
  • Li X , KaminskiNE, FischerLJ. Examination of the immunosuppressive effect of Δ9-tetrahydrocannabinol in streptozotocin-induced autoimmune diabetes.Int. Immunopharmacol.1, 699–712 (2001).
  • Weiss L , ZeiraM, ReichSet al. Cannabidiol lowers incidence of diabetes in non-obese diabetic mice. Autoimmunity 39, 143–151 (2006).
  • Weiss L , ZeiraM, ReichSet al. Cannabidiol arrests onset of autoimmune diabetes in NOD mice. Neuropharmacology 54, 244–249 (2008).
  • El-Remessy AB , Al-ShabraweyM, KhalifaY, TsaiNT, CaldwellRB, LiouGI. Neuroprotective and blood–retinal barrier-preserving effects of cannabidiol in experimental diabetes.Am. J. Pathol.168, 235–244 (2006).
  • Dogrul A , GulH, YildizO, BilginF, GuzeldemirME. Cannabinoids blocks tactile allodynia in diabetic mice without attenuation of its antinociceptive effect.Neurosci. Lett.368, 82–86 (2004).

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