Abstract
Cannabinoid-based drugs modeled on cannabinoids originally isolated from marijuana are now known to significantly impact the functioning of the endocannabinoid system of mammals. This system operates not only in the brain but also in organs and tissues in the periphery including the immune system. Natural and synthetic cannabinoids are tricyclic terpenes, whereas the endogenous physiological ligands are eicosanoids. Several receptors for these compounds have been extensively described, CB1 and CB2, and are G protein-coupled receptors; however, cannabinoid-based drugs are also demonstrated to function independently of these receptors. Cannabinoids regulate many physiological functions and their impact on immunity is generally antiinflammatory as powerful modulators of the cytokine cascade. This anti-inflammatory potency has led to the testing of these drugs in chronic inflammatory laboratory paradigms and even in some human diseases. Psychoactive and nonpsychoactive cannabinoid- based drugs such as ?9-tetrahydrocannabinol, cannabidiol, HU-211, and ajulemic acid have been tested and found moderately effective in clinical trials of multiple sclerosis, traumatic brain injury, arthritis, and neuropathic pain. Furthermore, although clinical trials are not yet reported, preclinical data with cannabinoid-based drugs suggest efficacy in other inflammatory diseases such as inflammatory bowel disease, Alzheimer’s disease, atherosclerosis, and osteoporosis.
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References
Anday, J.K. and Mercier, R.W. (2005) Gene ancestry of the cannabinoid receptor family. Pharmacol. Res. 20, 20.
Baker, D., Pryce, G., Croxford, J.L., Brown, P., Pertwee, R.G., Huffman, J.W. and Layward, L. (2000) Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature 404, 84–87.
Baker, D., Pryce, G., Davies, W.L. and Hiley, C.R. (2006) In silico patent searching reveals a new cannabinoid receptor. Trends Pharmacol. Sci. 27, 1–4.
Baldwin, G.C., Tashkin, D.P., Buckley, D.M., Park, A.N., Dubinett, S.M. and Roth, M.D. (1997) Marijuana and cocaine impair alveolar macrophage function and cytokine production. Am. J. Respir. Crit. Care Med. 156, 1606–1613.
Blake, D.R., Robson, P., Ho, M., Jubb, R.W. and McCabe, C.S. (2006) Preliminary assessment of the efficacy, tolerability and safety of a cannabis-based medicine (Sativex) in the treatment of pain caused by rheumatoid arthritis. Rheumatology (Oxford) 45, 50–52.
Breivogel, C.S., Griffin, G., Di Marzo, V. and Martin, B.R. (2001) Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol. Pharmacol. 60, 155–163.
Burstein, S.H., Friderichs, E., Kogel, B., Schneider, J. and Selve, N. (1998) Analgesic effects of 1’,1’ dimethylheptyl-delta8-THC-11-oic acid (CT3) in mice. Life Sci. 63, 161–168.
Cabral, G. and Dove Pettit, D. (1998) Drugs and immunity: cannabinoids and their role in decreased resistance to infectious diseases. J. Neuroimmunol. 83, 116–123.
Calignano, A., La Rana, G., Giuffrida, A. and Piomelli, D. (1998) Control of pain initiation by endogenous cannabinoids. Nature 394, 277–281.
Chang, Y.H., Lee, S.T. and Lin, W.W. (2001) Effects of cannabinoids on LPS-stimulated inflammatory mediator release from macrophages: involvement of eicosanoids. J. Cell. Biochem. 81, 715–723.
Croxford, J.L. and Miller, S.D. (2003) Immunoregulation of a viral model of multiple sclerosis using the synthetic cannabinoid R+WIN55,212. J. Clin. Invest. 111, 1231–1240.
Dajani, E.Z., Larsen, K.R., Taylor, J., Dajani, N.E., Shahwan, T.G., Neeleman, S.D., Taylor, M.S., Dayton, M.T. and Mir, G.N. (1999) 1’,1’-Dimethylheptyl-delta-8-tetrahydrocannabinol-11-oic acid: a novel, orally effective cannabinoid with analgesic and anti-inflammatory properties. J. Pharmacol. Exp. Ther. 291, 31–38.
Derocq, J.M., Jbilo, O., Bouaboula, M., Segui, M., Clere, C. and Casellas, P. (2000) 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.
Devane, W.A., Hanus, L., Breuer, A., Pertwee, R.G., Stevenson, L.A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A. and Mechoulam, R. (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258, 1946–1949.
Di Filippo, C., Rossi, F., Rossi, S. and D’Amico, M. (2004) Cannabinoid CB2 receptor activation reduces mouse myocardial ischemia-reperfusion injury: involvement of cytokine/chemokines and PMN. J. Leukoc. Biol. 75, 453–459. Epub 2003 Dec 2004.
Di Marzo, V. and Izzo, A.A. (2006) Endocannabinoid overactivity and intestinal inflammation. Gut 55, 1373–1376.
Ehrhart, J., Obregon, D., Mori, T., Hou, H., Sun, N., Bai, Y., Klein, T., Fernandez, F., Tan, J. and Shytle, R.D. (2005) Stimulation of cannabinoid receptor 2 (CB2) suppresses microglial activation. J. Neuroinflammation 2, 29.
Elmes, S.J., Winyard, L.A., Medhurst, S.J., Clayton, N.M., Wilson, A.W., Kendall, D.A. and Chapman, V. (2005) Activation of CB1 and CB2 receptors attenuates the induction and maintenance of inflammatory pain in the rat. Pain 118, 327–335.
Eubanks, L.M., Rogers, C.J., Beuscher, A.E., Koob, G.F., Olson, A.J., Dickerson, T.J. and Janda, K.D. (2006) A molecular link between the active component of marijuana and Alzheimer’s disease pathology. Mol. Pharm. 3, 773–777.
Fischer-Stenger, K., Dove Pettit, D.A. and Cabral, G.A. (1993) δ 9-Tetrahydrocannabinol inhibition of tumor necrosis factor-α : suppression of post-translational events. J. Pharm. Exp. Ther. 267, 1558–1565.
Fowler, C.J., Holt, S., Nilsson, O., Jonsson, K.O., Tiger, G. and Jacobsson, S.O. (2005) The endocannabinoid signaling system: pharmacological and therapeutic aspects. Pharmacol. Biochem. Behav. 81, 248–262.
Gaoni, Y. and Mechoulam, R. (1964) Isolation, structure, and partial synthesis of an active constituent of hashish. J. Am. Chem. Soc. 86, 1646–1647.
Gerard, C.M., Mollereau, C., Vassart, G. and Parmentier, M. (1991) Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem. J. 279, 129–134.
Hanus, L., Abu-Lafi, S., Fride, E., Breuer, A., Vogel, Z., Shalev, D.E., Kustanovich, I. and Mechoulam, R. (2001) 2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc. Natl. Acad. Sci. USA 98, 3662–3665.
Hohmann, A. and Suplita, R. (2006) Endocannabinoid mechanisms of pain modulation. AAPS J. 8, E693–E708.
Howlett, A.C., Breivogel, C.S., Childers, S.R., Deadwyler, S.A., Hampson, R.E. and Porrino, L.J. (2004) Cannabinoid physiology and pharmacology: 30 years of progress. Neuropharmacology 47, 345–358.
Ibrahim, M.M., Deng, H., Zvonok, A., Cockayne, D.A., Kwan, J., Mata, H.P., Vanderah, T.W., Lai, J., Porreca, F., Makriyannis, A. and Malan, T.P., Jr. (2003) Activation of CB2 cannabinoid receptors by AM1241 inhibits experimental neuropathic pain: pain inhibition by receptors not present in the CNS. Proc. Natl. Acad. Sci. USA 100, 10529–10533.
Idris, A.I., van ‘t Hof, R.J., Greig, I.R., Ridge, S.A., Baker, D., Ross, R.A. and Ralston, S.H. (2005) Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nat. Med. 11, 774–779.
Iskedjian, M., Bereza, B., Gordon, A., Piwko, C. and Einarson, T.R. (2007)Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain. Curr. Med. Res. Opin. 23, 17–24.
Jarai, Z., Wagner, J.A., Varga, K., Lake, K.D., Compton, D.R., Martin, B.R., Zimmer, A.M., Bonner, T.I., Buckley, N.E., Mezey, E., Razdan, R.K., Zimmer, A. and Kunos, G. (1999) Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors. Proc. Natl. Acad. Sci. USA 96, 14136–14141.
Karsak, M., Cohen-Solal, M., Freudenberg, J., Ostertag, A., Morieux, C., Kornak, U., Essig, J., Erxlebe, E., Bab, I., Kubisch, C., de Vernejoul, M.C. and Zimmer, A. (2005) Cannabinoid receptor type 2 gene is associated with human osteoporosis. Hum. Mol. Genet. 14, 3389–3396.
Karst, M., Salim, K., Burstein, S., Conrad, I., Hoy, L. and Schneider, U. (2003) Analgesic effect of the synthetic cannabinoid CT-3 on chronic neuropathic pain: a randomized controlled trial. JAMA 290, 1757–1762.
Kishimoto, S., Kobayashi, Y., Oka, S., Gokoh, M., Waku, K. and Sugiura, T. (2004) 2-Arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces accelerated production of chemokines in HL-60 cells. J. Biochem. (Tokyo) 135, 517–524.
Klein, T.W. (2005) Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat. Rev. Immunol. 5, 400–411.
Klein, T.W. and Cabral, G. (2006) Cannabinoid-induced immune suppression and modulation of antigen-presenting cells. J. Neuroimmune Pharmacol. 1, 50–64.
Klein, T.W., Lane, B., Newton, C.A. and Friedman, H. (2000a) The cannabinoid system and cytokine network. Proc. Soc. Exp. Biol. Med. 225, 1–8.
Klein, T., Newton, C. and Friedman, H. (1998) Cannabinoid receptors and immunity. Immunol. Today 19, 373–381.
Klein, T.W., Newton, C., Larsen, K., Lu, L., Perkins, I., Nong, L. and Friedman, H. (2003) The cannabinoid system and immune modulation. J. Leukoc. Biol. 74, 486–496.
Klein, T.W., Newton, C.A., Nakachi, N. and Friedman, H. (2000b) δ 9-Tetrahydrocannabinol treatment suppresses immunity and early IFNγ , IL-12, and IL-12 receptor β 2 responses to Legionella pneumophila infection. J. Immunol. 164, 6461–6466.
Klein, T.W., Newton, C., Widen, R. and Friedman, H. (1993) δ 9- Tetrahydrocannabinol injection induces cytokine-mediated mortality of mice infected with Legionella pneumophila. J. Pharmacol. Exp. Ther. 267, 635–640.
Knoller, N., Levi, L., Shoshan, I., Reichenthal, E., Razon, N., Rappaport, Z.H. and Biegon, A. (2002) Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomized, placebo-controlled, phase II clinical trial. Crit. Care Med. 30, 548–554.
Liu, J., Li, H., Burstein, S.H., Zurier, R.B. and Chen, J.D. (2003) Activation and binding of peroxisome proliferator-activated receptor gamma by synthetic cannabinoid ajulemic acid. Mol. Pharmacol. 63, 983–992.
Lu, T., Newton, C., Perkins, I., Friedman, H. and Klein, T.W. (2006) Role of cannabinoid receptors in Delta-9-tetrahydrocannabinol suppression of IL-12p40 in mouse bone marrow-derived dendritic cells infected with Legionella pneumophila. Eur. J. Pharmacol. 532, 170–177.
Lyman, W.D., Sonett, J.R., Brosnan, C.F., Elkin, R. and Bornstein, M.B. (1989) δ 9-Tetrahydrocannabinol: a novel treatment for experimental autoimmune encephalomyelitis. J. Neuroimmunol. 23, 73–81.
Maas, A.I., Murray, G., Henney, H., 3rd, Kassem, N., Legrand, V., Mangelus, M., Muizelaar, J.P., Stocchetti, N. and Knoller, N. (2006) Efficacy and safety of dexanabinol in severe traumatic brain injury: results of a phase III randomised, placebo-controlled, clinical trial. Lancet Neurol. 5, 38–45.
Mackenzie, I.R., Hao, C. and Munoz, D.G. (1995) Role of microglia in senile plaque formation. Neurobiol. Aging 16, 797–804.
Malfait, A.M., Gallily, R., Sumariwalla, P.F., Malik, A.S., Andreakos, E., Mechoulam, R. and Feldmann, M. (2000) The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis [see comments]. Proc. Natl. Acad. Sci. USA 97, 9561–9566.
Marsicano, G., Goodenough, S., Monory, K., Hermann, H., Eder, M., Cannich, A., Azad, S.C., Cascio, M.G., Gutierrez, S.O., van der Stelt, M., Lopez-Rodriguez, M.L., Casanova, E., Schutz, G., Zieglgansberger, W., Di Marzo, V., Behl, C. and Lutz, B. (2003) CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science. 302, 84–88.
Massa, F., Storr, M. and Lutz, B. (2005) The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract. J. Mol. Med. 26, 26.
Mathison, R., Ho, W., Pittman, Q.J., Davison, J.S. and Sharkey, K.A. (2004) Effects of cannabinoid receptor-2 activation on accelerated gastrointestinal transit in lipopolysaccharide-treated rats. Br. J. Pharmacol. 142, 1247–1254.
Matsuda, L.A., Lolait, S.J., Brownstein, M.J., Young, A.C. and Bonner, T.I. (1990) Structure of cannabinoid receptor and functional expression of the cloned cDNA. Nature 346, 561–564.
Mechoulam, R., Ben-Shabat, S., Hanus, L., Ligumsky, M., Kaminski, N.E., Schatz, A.R., Gopher, A., Almog, S., Martin, B.R., Compton, D.R., Pertwee, R.G., Griffin, G., Bayewitch, M., Barg, J. and Vogel, Z. (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharm. 50, 83–90.
Mechoulam, R., Panikashvili, D. and Shohami, E. (2002) Cannabinoids and brain injury: therapeutic implications. Trends Mol. Med. 8, 58–61.
Milton, N.G. (2002) Anandamide and noladin ether prevent neurotoxicity of the human amyloid-beta peptide. Neurosci. Lett. 332, 127–130.
Mitchell, V.A., Aslan, S., Safaei, R. and Vaughan, C.W. (2005) Effect of the cannabinoid ajulemic acid on rat models of neuropathic and inflammatory pain. Neurosci. Lett. 382, 231–235.
Munro, S., Thomas, K.L. and Abu-Shaar, M. (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365, 61–65.
Nahas, G.G., Suciu-Foca, N., Armand, J.-P. and Morishima, A. (1974) Inhibition of cellular mediated immunity in marihuana smokers. Science 183, 419–420.
Newton, C.A., Klein, T.W. and Friedman, H. (1994) Secondary immunity to Legionella pneumophila and Th1 activity are suppressed by delta- 9-tetrahydrocannabinol injection. Infect. Immun. 62, 4015–4020.
Nogid, A. and Pham, D.Q. (2006) Role of abatacept in the management of rheumatoid arthritis. Clin Ther. 28, 1764–1778.
Ofek, O., Karsak, M., Leclerc, N., Fogel, M., Frenkel, B., Wright, K., Tam, J., Attar-Namdar, M., Kram, V., Shohami, E., Mechoulam, R., Zimmer, A. and Bab, I. (2006) Peripheral cannabinoid receptor, CB2, regulates bone mass. Proc. Natl. Acad. Sci. U S A. 103, 696–701.
Offertaler, L., Mo, F.M., Batkai, S., Liu, J., Begg, M., Razdan, R.K., Martin, B.R., Bukoski, R.D. and Kunos, G. (2003) Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor. Mol. Pharmacol. 63, 699–705.
Pacher, P., Batkai, S. and Kunos, G. (2006) The endocannabinoid system as an emerging target of pharmacotherapy. Pharmacol. Rev. 58, 389–462.
Pacifici, R., Zuccaro, P., Pichini, S., Roset, P.N., Poudevida, S., Farre, M., Segura, J. and De la Torre, R. (2003) Modulation of the immune system in cannabis users. JAMA 289, 1929–1931.
Panikashvili, D., Simeonidou, C., Ben-Shabat, S., Hanus, L., Breuer, A., Mechoulam, R. and Shohami, E. (2001) An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature 413, 527–531.
Pertwee, R.G. (2005) The therapeutic potential of drugs that target cannabinoid receptors or modulate the tissue levels or actions of endocannabinoids. AAPS J. 7, E625–E654.
Pinto, L., Izzo, A.A., Cascio, M.G., Bisogno, T., Hospodar-Scott, K., Brown, D.R., Mascolo, N., Di Marzo, V. and Capasso, F. (2002) Endocannabinoids as physiological regulators of colonic propulsion in mice. Gastroenterology 123, 227–234.
Porter, A.C., Sauer, J.M., Knierman, M.D., Becker, G.W., Berna, M.J., Bao, J., Nomikos, G.G., Carter, P., Bymaster, F.P., Leese, A.B. and Felder, C.C. (2002) Characterization of a novel endocannabinoid, virodhamine, with antagonist activity at the CB1 receptor. J. Pharmacol. Exp. Ther. 301, 1020–1024.
Pryce, G., Ahmed, Z., Hankey, D.J., Jackson, S.J., Croxford, J.L., Pocock, J.M., Ledent, C., Petzold, A., Thompson, A.J., Giovannoni, G., Cuzner, M.L. and Baker, D. (2003) Cannabinoids inhibit neurodegeneration in models of multiple sclerosis. Brain 126, 2191–2202.
Pryce, G. and Baker, D. (2007) Control of spasticity in a multiple sclerosis model is mediated by CB(1), not CB(2), cannabinoid receptors. Br. J. Pharmacol. 15, 15.
Ramirez, B.G., Blazquez, C., Gomez del Pulgar, T., Guzman, M. and de Ceballos, M.L. (2005) Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation. J. Neurosci. 25, 1904–1913.
Rodan, G.A. and Martin, T.J. (2000) Therapeutic approaches to bone diseases. Science 289, 1508–1514.
Rog, D.J., Nurmikko, T.J., Friede, T. and Young, C.A. (2005) Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology 65, 812–819.
Rousseaux, C., Thuru, X., Gelot, A., Barnich, N., Neut, C., Dubuquoy, L., Dubuquoy, C., Merour, E., Geboes, K., Chamaillard, M., Ouwehand, A., Leyer, G., Carcano, D., Colombel, J.F., Ardid, D. and Desreumaux, P. (2007) Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nat. Med. 13, 35–37.
Salim, K., Schneider, U., Burstein, S., Hoy, L. and Karst, M. (2005) Pain measurements and side effect profile of the novel cannabinoid ajulemic acid. Neuropharmacology 48, 1164–1171.
Shohami, E., Gallily, R., Mechoulam, R., Bass, R. and Ben-Hur, T. (1997) Cytokine production in the brain following closed head injury: dexanabinol (HU-211) is a novel TNF-alpha inhibitor and an effective neuroprotectant. J. Neuroimmunol. 72, 169–177.
Shohami, E., Novikov, M. and Bass, R. (1995) Long-term effect of HU-211, a novel non-competitive NMDA antagonist, on motor and memory functions after closed head injury in the rat. Brain Res. 674, 55–62.
Smith, S.R., Terminelli, C. and Denhardt, G. (2000) 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.
Steffens, S., Veillard, N.R., Arnaud, C., Pelli, G., Burger, F., Staub, C., Karsak, M., Zimmer, A., Frossard, J.L. and Mach, F. (2005) Low dose oral cannabinoid therapy reduces progression of atherosclerosis in mice. Nature. 434, 782–786.
Sumariwalla, P.F., Gallily, R., Tchilibon, S., Fride, E., Mechoulam, R. and Feldmann, M. (2004) A novel synthetic, nonpsychoactive cannabinoid acid (HU-320) with antiinflammatory properties in murine collagen-induced arthritis. Arthritis Rheum. 50, 985–998.
Sun, Y., Alexander, S.P., Kendall, D.A. and Bennett, A.J. (2006) Cannabinoids and PPARalpha signalling. Biochem. Soc. Trans. 34, 1095–1097.
Svendsen, K.B., Jensen, T.S. and Bach, F.W. (2004) Does the cannabinoid dronabinol reduce central pain in multiple sclerosis? Randomised double blind placebo controlled crossover trial. BMJ 329, 253.
Takeda, S., Elefteriou, F., Levasseur, R., Liu, X., Zhao, L., Parker, K.L., Armstrong, D., Ducy, P. and Karsenty, G. (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell 111, 305–317.
Tomida, I., Pertwee, R.G. and Azuara-Blanco, A. (2004) Cannabinoids and glaucoma. Br. J. Ophthalmol. 88, 708–713.
Van Gaal, L.F., Rissanen, A.M., Scheen, A.J., Ziegler, O. and Rossner, S. (2005) 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 365, 1389–1397.
Vaney, C., Heinzel-Gutenbrunner, M., Jobin, P., Tschopp, F., Gattlen, B., Hagen, U., Schnelle, M. and Reif, M. (2004) Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis: a randomized, double-blind, placebo-controlled, crossover study. Mult. Scler. 10, 417–424.
Varga, K., Wagner, J.A., Bridgen, D.T. and Kunos, G. (1998) Platelet- and macrophage-derived endogenous cannabinoids are involved in endotoxin-induced hypotension. FASEB J. 12, 1035–1044.
Wade, D.T., Makela, P., Robson, P., House, H. and Bateman, C. (2004) Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients. Mult. Scler. 10, 434–441.
Wagner, J.A., Varga, K., Kunos, G. and Bridgen, D.T. (1998) Cardiovascular actions of cannabinoids and their generation during shock: platelet- and macrophage-derived endogenous cannabinoids are involved in endotoxin-induced hypotension. J. Mol. Med. 76, 824–836.
Wang, Y., Liu, Y., Ito, Y., Hashiguchi, T., Kitajima, I., Yamakuchi, M., Shimizu, H., Matsuo, S., Imaizumi, H. and Maruyama, I. (2001) Simultaneous measurement of anandamide and 2-arachidonoylglycerol by polymyxin B-selective adsorption and subsequent high-performance liquid chromatography analysis: increase in endogenous cannabinoids in the sera of patients with endotoxic shock. Anal. Biochem. 294, 73–82.
Wirguin, I., Mechoulam, R., Breuer, A., Schezen, E., Weidenfeld, J. and Brenner, T. (1994) Suppression of experimental autoimmune encephalomyelitis by cannabinoids. Immunopharmacolology 28, 209–214.
Wright, K., Rooney, N., Feeney, M., Tate, J., Robertson, D., Welham, M. and Ward, S. (2005) Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing. Gastroenterology 129, 437–453.
Yuan, M., Kiertscher, S.M., Cheng, Q., Zoumalan, R., Tashkin, D.P. and Roth, M.D. (2002) D9-tetrahydrocannabinol regulates Th1/Th2 cytokine balance in activated human T cells. J. Neuroimmunol. 133, 124–131.
Zajicek, J., Fox, P., Sanders, H., Wright, D., Vickery, J., Nunn, A. and Thompson, A. (2003) Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study): multicentre randomised placebo-controlled trial. Lancet 362, 1517–1526.
Zajicek, J.P., Sanders, H.P., Wright, D.E., Vickery, P.J., Ingram, W.M., Reilly, S.M., Nunn, A.J., Teare, L.J., Fox, P.J. and Thompson, A.J. (2005)Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up. J. Neurol. Neurosurg. Psychiatry 76, 1664–1669.
Zhu, W., Newton, C., Daaka, Y., Friedman, H. and Klein, T.W. (1994) δ 9-Tetrahydrocannabinol enhances the secretion of interleukin 1 from endotoxin-stimulated macrophages. J. Pharmacol. Exp. Ther. 270, 1334–1339.
Zhu, L.X., Sharma, S., Stolina, M., Gardner, B., Roth, M.D., Tashkin, D.P.and Dubinett, S.M. (2000) δ -9-Tetrahydrocannabinol inhibits antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway. J. Immunol. 165, 373–380.
Zurier, R.B., Rossetti, R.G., Burstein, S.H. and Bidinger, B. (2003) Suppression of human monocyte interleukin-1beta production by ajulemic acid, a nonpsychoactive cannabinoid. Biochem. Pharmacol. 65, 649–655.
Zurier, R.B., Rossetti, R.G., Lane, J.H., Goldberg, J.M., Hunter, S.A. and Burstein, S.H. (1998) Dimethylheptyl-THC-11-oic acid. A nonpsychoactive antiinflammatory agent with a cannabinoid template structure. Arthritis Rheum. 41, 163–170.
Zygmunt, P.M., Petersson, J., Andersson, D.A., Chuang, H., Sorgard, M., Di Marzo, V., Julius, D. and Hogestatt, E.D. (1999) Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature 400, 452–457.
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Klein, T.W., Newton, C.A. (2007). Therapeutic Potential of Cannabinoid-Based Drugs. In: Shurin, M.R., Smolkin, Y.S. (eds) Immune-Mediated Diseases. Advances in Experimental Medicine and Biology, vol 601. Springer, New York, NY. https://doi.org/10.1007/978-0-387-72005-0_43
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