Skip to main content
Log in

Effects of Cannabinoids on the Immune System and Central Nervous System

Therapeutic Implications

  • Leading Article
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

This review aims to improve understanding of the modulatory effects that cannabinoids exert on the immune system and CNS. Cannabinoids possess immunomodulatory activity, are neuroprotective in vivo and in vitro and can modify the production of inflammatory mediators, such as nitric oxide, prostanoids and cytokines, that are expressed by, and act on, the immune system and the brain. The mechanisms of cannabinoid actions are not fully understood, but appear to involve complex interactions between cannabinoid receptors and a number of signal transduction pathways. Endogenous cannabinoid ligands appear to act as local modulators of immune/inflammatory reactions.

Cannabinoid-induced immunosuppression may have implications for the treatment of neurological disorders that are associated with excess immunological activity, such as multiple sclerosis and Alzheimer’s disease. There is anecdotal evidence that cannabis use improves the symptoms of multiple sclerosis, and studies with animal models are beginning to provide evidence for the mechanism of such effects. The development of nonpsychotropic cannabinoid analogues and modulators of the metabolism of endogenous cannabinoid ligands may lead to novel approaches to the treatment of neurodegenerative disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Mechoulam R. The pharmacology of Cannabis sativa. In: Mechoulam R, editor. Cannabinoids as therapeutic agents. Boca Raton (FL): CRC, 1986: 1–19

    Google Scholar 

  2. Gaoni Y, Mechoulam R. Isolation, structure elucidation and partial synthesis of an active constituent of hashish. J Am Chem Soc 1964; 1646-47: 11–20

    Google Scholar 

  3. Matsuda LA, Lolait SJ, Brownstein MJ, et al. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 1990; 346: 561–4

    PubMed  CAS  Google Scholar 

  4. Shire D, Carillon C, Kaghad M, et al. An amino-terminal variant of the central cannabinoid receptor resulting from alternative splicing. J Biol Chem 1995; 270: 3726–31

    PubMed  CAS  Google Scholar 

  5. Munro S, Thomas KL, Abu-Shaar M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 1993; 365: 61–5

    PubMed  CAS  Google Scholar 

  6. Stefano GB, Liu Y, Goligorsky MS, et al. Cannabinoid receptors are coupled to nitric oxide release in invertebrate immunocytes, microglia, and human monocytes. J Biol Chem 1996; 271(32): 19238–42

    PubMed  CAS  Google Scholar 

  7. Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992; 258: 1946–9

    PubMed  CAS  Google Scholar 

  8. Mechoulam R, Ben-Shabat S, Hanus L, et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 1995; 50: 83–90

    PubMed  CAS  Google Scholar 

  9. Felder CC, Veluz JS, Williams HL, et al. Cannabinoid agonists stimulate both receptor and non-receptor-mediated signal transduction pathways in cells transfected with and expressing cannabinoid receptor clones. Mol Pharmacol 1992; 42: 838–45

    PubMed  CAS  Google Scholar 

  10. Kaminski NE, Abood ME, Kessler FK, et al. Identification of a functionally relevant cannabinoid receptor on mouse spleen cells that is involved in cannabinoid-mediated immune modulation. Mol Pharmacol 1992; 42: 736–42

    PubMed  CAS  Google Scholar 

  11. Kiein TW, Friedman H, Specter S. Marijuana, immunity and infection. J Neuroimmunol 1998; 83: 102–15

    Google Scholar 

  12. Kiein TW, Newton C, Friedman H. Cannabinoid receptors and immunity. Imunol Today 1998; 19: 373–81

    Google Scholar 

  13. Jeon YJ, Yang KH, Pulaski JT, et al. Attenuation of inducible nitric oxide synthase gene expression by delta 9-tetrahydro-cannabinol is mediated through the inhibition of nuclear factor-kappa B/Rel activation. Mol Pharmacol 1996; 50: 334–41

    PubMed  CAS  Google Scholar 

  14. Molina-Holgado F, Lledo A, Guaza C. Anandamide suppresses nitric oxide and TNF-alpha responses to Theiler’s virus or endotoxin in astrocytes. Neuroreport 1997; 8: 1929–33

    PubMed  CAS  Google Scholar 

  15. Molina-Holgado F, Molina-Holgado E, Guaza C. The endogenous cannabinoid anandamide potentiates interleukin-6 production by astrocytes infected with Theiler’s murine encephalomyelitis virus by a receptor-mediated pathway. FEBS Lett 1998; 433: 139–42

    PubMed  CAS  Google Scholar 

  16. Lyman WD, Sonett JR, Brosnan CF, et al. Delta 9-tetrahydro-cannabinol: a novel treatment for experimental autoimmune encephalomyelitis. J Neuroimmunol 1989; 23: 73–81

    PubMed  CAS  Google Scholar 

  17. Wirguin I, Mechoulam R, Breuer A, et al. Suppression of experimental autoimmune encephalomyelitis by cannabinoids. Immunopharmacology 1994; 28: 209–14

    PubMed  CAS  Google Scholar 

  18. Zheng ZM, Specter S. Suppression by delta-9-tetrahydrocannabinol of lipopolysaccharide induced and intrinsic tyrosine phosphorylation and protein expression in mouse peritoneal macrophages. Biochem Pharmacol 1994; 47: 2243–52

    Google Scholar 

  19. Juel-Jensen BE. Cannabis and recurrent herpes simplex [letter]. Br Med J 1972; 4(835): 296

    PubMed  CAS  Google Scholar 

  20. Schatz AR, Koh WS, Kaminski NE. Delta 9-tetrahydrocannabinol selectively inhibits T-cell dependent humoral immune responses through direct inhibition of accessory T-cell function. Immunopharmacology 1993; 26: 129–37

    PubMed  CAS  Google Scholar 

  21. Schatz AR, Lee M, Condie RB, et al. Cannabinoid receptors CB1 and CB2: a characterization of expression and adenylate cyclase modulation within the immune system. Toxicol Appl Pharmacol 1997; 142: 278–87

    PubMed  CAS  Google Scholar 

  22. Lee M, Yang KH, Kaminski NE. Effects of putative cannabinoid receptor ligands, anandamide and 2-arachidonyl-glycerol, on immune function in B6C3F1 mouse splenocytes. J Pharmacol Exp Ther 1995; 275: 529–36

    PubMed  CAS  Google Scholar 

  23. Lynn AB, Herkenham M. Localization of cannabinoid receptors and nonsaturable high-density cannabinoid binding sites in peripheral tissues of the rat: implications for receptor-mediated immune modulation by cannabinoids. J Pharmacol Exp Ther 1994; 268: 1612–23

    PubMed  CAS  Google Scholar 

  24. Cabrai GA, Dove Pettit DA. Drugs and immunity: cannabinoids and their role in decreased resistance to infectious disease. J Neuroimmunol 1998; 83: 116–23

    Google Scholar 

  25. Cabrai GA, Lockmuller JC, Mishkin EM. Delta 9-tetrahydrocannabinol decreases alpha/beta interferon response to herpes simplex virus type 2 in the B6C3F1 mouse. Proc Soc Exp Biol Med 1986; 181(2): 305–11

    Google Scholar 

  26. Smith MS, Yamamoto Y, Newton C, et al. Psychoactive cannabinoids increase mortality and alter acute phase cytokine responses in mice sublethally infected with Legionella pneumophila. Proc Soc Exp Biol Med 1997; 214(1): 69–75

    PubMed  CAS  Google Scholar 

  27. Ongradi J, Specter S, Horvath A, et al. Combined in vitro effect of marijuana and retrovirus on the activity of mouse natural killer cells. Pathol Oncol Res 1998; 4(3): 191–9

    PubMed  CAS  Google Scholar 

  28. Coffey RG, Snella E, Johnson K, et al. Inhibition of macrophage nitric oxide production by tetrahydrocannabinol in vivo and in vitro. Int J Immunopharmacol 1996; 18(12): 749–52

    PubMed  CAS  Google Scholar 

  29. Coffey RG, Yamamoto Y, Snella E, et al. Tetrahydrocannabinol inhibition of macrophage nitric oxide production. Biochem Pharmacol 1996; 52(5): 743–51

    PubMed  CAS  Google Scholar 

  30. Ovadia H, Wohlman A, Mechoulam R, et al. Characterization of the hypothermic effect of the synthetic cannabinoid HU-210 in the rat. Relation to the adrenergic system and endogenous pyrogens. Neuropharmacology 1995; 34(2): 1175–80

    Google Scholar 

  31. Patrini G, Sacerdote P, Fuzio D, et al. Regulation of immune functions in rat splenocytes after acute and chronic in vivo treatment with CP-55,940, a synthetic cannabinoid compound. J Neuroimmunol 1997; 80(1-2): 1143–8

    Google Scholar 

  32. Nahas GG, Suciu-Foca N, Armand JP, et al. Inhibition of cellular mediated immunity in marihuana smokers. Science 1974; 183(123): 419–20

    PubMed  CAS  Google Scholar 

  33. White SC, Brin SC, Janicki BW. Mitogen-induced blastogenic responses of lymphocytes from marihuana smokers. Science 1975; 188(4183): 71–2

    PubMed  CAS  Google Scholar 

  34. Rachelefsky GS, Opelz G, Mickey MR, et al. Intact humoral and cell-mediated immunity in chronic marijuana smoking. J Allergy Clin Immunol 1976; 58(4): 483–90

    PubMed  CAS  Google Scholar 

  35. Nahas GG, Oserman GS. Altered serum immunoglobulin concentration in chronic marijuana smokers. Adv Exp Biol Med 1991; 288: 25–32

    CAS  Google Scholar 

  36. Dax EM, Pilotte NS, Adler WH, et al. The effects of 9-ene-tetrahydrocannabinol on hormone release and immune function. J Steroid Biochem 1989; 34(1-6): 263–70

    PubMed  CAS  Google Scholar 

  37. Massi P, Sacerdote P, Ponti W, et al. Immune function alterations in mice tolerant to delta9-tetrahydrocannabinol: functional and biochemical parameters. J Neuroimmunol 1998; 92(1-2): 60–6

    PubMed  CAS  Google Scholar 

  38. Kawakami Y, Klein TW, Newton C, et al. Suppression by cannabinoids of a cloned cell line with natural killer cell activity. Proc Soc Exp Biol Med 1988; 187(3): 355–9

    PubMed  CAS  Google Scholar 

  39. Ouyang Y, Hwang SG, Han SH, et al. Suppression of interleukin-2 by the putative endogenous cannabinoid 2-arachidonyl-glycerol is mediated through down-regulation of the nuclear factor of activated T cells. Mol Pharmacol 1998; 53: 676–83

    PubMed  CAS  Google Scholar 

  40. Klein TW, Newton C, Friedman H. Cannabinoid receptors and the cytokine network. Adv Exp Biol Med 1998; 437: 215–22

    CAS  Google Scholar 

  41. Friedman H, Klein T, Specter S, et al. Drugs of abuse and virus susceptibility. Adv Biochem Psychopharmacol 1988; 44: 125–37

    PubMed  CAS  Google Scholar 

  42. Burnette-Curley D, Cabrai GA. Differential inhibition of RAW264.7 macrophage tumoricidal activity by delta 9 tetra-hydrocannabinol. Proc Soc Exp Biol Med 1995; 210(1): 64–76

    PubMed  CAS  Google Scholar 

  43. Gallily R, Yamin A, Waksman Y, et al. Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production by dexanabinol (HU-211), a non-psychotropic cannabinoid. J Pharmacol Exp Ther 1997; 283: 918–24

    PubMed  CAS  Google Scholar 

  44. Varga K, Wagner JA, Bridgen DT, et al. Platelet and macro-phage-derived endogenous cannabinoids are involved in endotoxin-induced hypotension. FASEB J 1998; 11: 1035–44

    Google Scholar 

  45. Schwarz H, Blanco FJ, Lotz M. Anandamide, an endogenous cannabinoid receptor agonist inhibits lymphocyte proliferation and induces apoptosis. J Neuroimmunol 1994; 55:107–15

    PubMed  CAS  Google Scholar 

  46. Zhu W, Friedman H, Klein TW. Delta9-tetrahydrocannabinol induces apoptosis in macrophages and lymphocytes: involvement of Bcl-2 and caspase-1. J Pharmacol Exp Ther 1998; 286(2): 1103–9

    PubMed  CAS  Google Scholar 

  47. Zheng ZM, Specter S, Friedman H. Inhibition by delta-9-tetra-hydrocannabinol of tumor necrosis factor alpha production by mouse and human macrophages. Int J Immunopharmacol 1992; 14(8): 1445–52

    PubMed  CAS  Google Scholar 

  48. Condie R, Herring A, Koh WS, et al. Cannabinoid inhibition of adenylate cyclase-mediated signal transduction and interleukin 2 (IL-2) expression in the murine T-cell line, EL4.IL-2. J Biol Chem 1996; 271: 13175–83

    PubMed  CAS  Google Scholar 

  49. Herring AC, Koh WS, Kaminski NE. Inhibition of the cyclic AMP signaling cascade and nuclear factor binding to CRE and kappaB elements by cannabinol, a minimally CNS-active cannabinoid. Biochem Pharmacol 1998; 55(7): 1013–23

    PubMed  CAS  Google Scholar 

  50. Snella E, Pross S, Friedman H. Relationship of aging and cytokines to the immunomodulation by delta-9-tetrahydro-cannabinol on murine lymphoid cells. Int J Immunopharmacol 1995; 17(112): 1045–54

    PubMed  CAS  Google Scholar 

  51. Nakano Y, Pross S, Friedman H. Contrasting effect of delta-9-tetrahydrocannabinol on IL-2 activity in spleen and lymph node cells of mice of different ages. Life Sci 1993; 52: 41–51

    PubMed  CAS  Google Scholar 

  52. Valk P, Verbakel S, Vankan Y, et al. Anandamide, a natural ligand for the peripheral cannabinoid receptor is a novel synergistic growth factor for hematopoietic cells. Blood 1997; 90: 1448–57

    PubMed  CAS  Google Scholar 

  53. Berdyshev EV, Boichot E, Germain N, et al. Influence of fatty acid ethanolamides and delta9-tetrahydrocannabinol on cytokine and arachidonate release by mononuclear cells. Eur J Pharmacol 1997; 330(2–3): 231–40

    PubMed  CAS  Google Scholar 

  54. Stefano GB, Salzet M, Rialas CM. Macrophage behavior associated with acute and chronic exposure to HIV GP 120, morphine and anandamide: endothelial implications. Int J Cardiol 1998; 64Suppl. 1: S3–13

    PubMed  Google Scholar 

  55. Shivers SC, Newton C, Friedman H, et al. Delta 9-tetrahydro-cannabinol (THC) modulates IL-1 bioactivity in human monocyte/macrophage cell lines. Life Sci 1994; 54(17): 1281–9

    PubMed  CAS  Google Scholar 

  56. Bouaboula M, Poinot-Chazel C, Bourrie B, et al. Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1. Biochem J 1995; 312 (Pt 2): 637–41

    PubMed  CAS  Google Scholar 

  57. Trisler K, Specter S. Delta-9-tetrahydrocannabinol treatment results in a suppression of interleukin-2-induced cellular activities in human and murine lymphocytes. Int J Immunopharmacol 1994; 16(7): 593–603

    PubMed  CAS  Google Scholar 

  58. Kusher DI, Dawson LO, Taylor AC, et al. Effect of the psychoactive metabolite of marijuana, delta 9-tetrahydrocan-nabinol (THC), on the synthesis of tumor necrosis factor by human large granular lymphocytes. Cell Immunol 1994; 154(1): 99–108

    PubMed  CAS  Google Scholar 

  59. Daaka Y, Zhu W, Friedman H, et al. Induction of interleukin-2 receptor alpha gene by delta9-tetrahydrocannabinol is mediated by nuclear factor kappaB and CB1 cannabinoid receptor. DNA Cell Biol 1997; 16(3): 301–9

    PubMed  CAS  Google Scholar 

  60. Srivastava MD, Srivastava BI, Brouhard B. Delta9 tetrahydro-cannabinol and cannabidiol alter cytokine production by human immune cells. Immunopharmacology 1998; 40(3): 179–85

    PubMed  CAS  Google Scholar 

  61. Bouaboula M, Poinot-Chazel C, Marchand J, et al. Signaling pathway associated with stimulation of CB2 peripheral cannabinoid receptor. Involvement of both mitogen-activated protein kinase and induction of Krox-24 expression. Eur J Biochem 1996; 237: 704–11

    PubMed  CAS  Google Scholar 

  62. Wartmann M, Campbell D, Subramanian A, et al. The MAP kinase signal transduction pathway is activated by the endogenous cannabinoid anandamide. FEBS Lett 1995; 359: 133–6

    PubMed  CAS  Google Scholar 

  63. Watzl B, Scuderi P, Watson RR. Marijuana components stimulate human peripheral blood mononuclear cell secretion of interferon-gamma and suppress interleukin-1 alpha in vitro. Int J Immunopharmacol 1991; 13(8): 1091–7

    PubMed  CAS  Google Scholar 

  64. Bisogno T, Maurellis S, Melck D, et al. Biosynthesis, uptake, and degradation of anandamide and palmitoylethanolamide in leukocytes. J Biol Chem 1997; 272: 3315–23

    PubMed  CAS  Google Scholar 

  65. Derocq JM, Segui M, Marchand J, et al. Cannabinoids enhance human B-cell growth at low nanomolar concentrations. FEBS Lett 1995; 369: 177–82

    PubMed  CAS  Google Scholar 

  66. Fischer-Stenger K, Updegrove AW, Cabrai GA. Delta 9-tetrahydrocannabinol decreases cytotoxic T lymphocyte activity to herpes simplex virus type 1-infected cells. Proc Soc Exp Biol Med 1992; 200: 422–30

    PubMed  CAS  Google Scholar 

  67. Fischer-Stenger K, Dove Pettit DA, et al. Delta 9-tetrahydro-cannabinol inhibition of tumor necrosis factor-alpha: suppression of post-translational events. J Pharmacol Exp Ther 1993; 267(3): 1558–65

    PubMed  CAS  Google Scholar 

  68. Bouaboula M, Rinaldi M, Carayon P, et al. Cannabinoid-receptor expression in human leukocytes. Eur J Biochem 1993; 214(1): 173–80

    PubMed  CAS  Google Scholar 

  69. Valk PJ, Delwel R. The peripheral cannabinoid receptor, Cb2, in retrovirally-induced leukemic transformation and normal hematopoiesis. Leuk Lymphoma 1998; 32(1–2): 29–43

    PubMed  CAS  Google Scholar 

  70. Felder CC, Glass M. Cannabinoid receptors and their endogenous agonists. Annu Rev Pharmacol Toxicol 1998; 38: 179–200

    PubMed  CAS  Google Scholar 

  71. Gonzalez GA, Montminy MR. Cyclic AMP stimulates somatostatin gene transcription by phosphorylation of CREB at serine 133. Cell 1989; 59: 675–80

    PubMed  CAS  Google Scholar 

  72. Derocq JM, Bouaboula M, Marchand J, et al. The endogenous cannabinoid anandamide is a lipid messenger activating cell growth via a cannabinoid receptor-independent pathway in hematopoietic cell lines. FEBS Lett 1998; 425: 419–25

    PubMed  CAS  Google Scholar 

  73. Rinaldi-Carmona M, Barth F, Millan J, et al. SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor. J Pharmacol Exp Ther 1998; 284: 644–50

    PubMed  CAS  Google Scholar 

  74. Stuehr DJ, Nathan CF. Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J Exp Med 1989; 169: 1543–55

    PubMed  CAS  Google Scholar 

  75. Feng L, Sun W, Xia Y, et al. Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression. Arch Biochem Biophys 1993; 307(2): 361–8

    PubMed  CAS  Google Scholar 

  76. Yu M, Ives D, Ramesha CS. Synthesis of prostaglandin E2 ethanolamide from anandamide by cyclooxygenase-2. J Biol Chem 1997; 272: 21181–6

    PubMed  CAS  Google Scholar 

  77. Shen M, Thayer SA. Cannabinoid receptor agonists protect cultured rat hippocampal neurons from excitotoxicity. Mol Pharmacol 1998; 54(3): 459–62

    PubMed  CAS  Google Scholar 

  78. Nagayama T, Sinor AD, Simon RP, et al. Cannabinoids and neuroprotection in global and focal cerebral ischemia and in neuronal cultures. J Neurosci 1999; 19(8): 2987–95

    PubMed  CAS  Google Scholar 

  79. Blazquez C, Sanchez C, Daza A, et al. The stimulation of ketogenesis by cannabinoids in cultured astrocytes defines carnitine palmitoyltransferase I as a new ceramide-activated enzyme. J Neurochem 1999; 72(4): 1759–68

    PubMed  CAS  Google Scholar 

  80. Sanchez C, Galve-Roperh I, Rueda D, et al. Involvement of sphingomyelin hydrolysis and the mitogen-activated protein kinase cascade in the delta-9-tetrahydrocannabinol-induced stimulation of glucose metabolism in primary astrocytes. Mol Pharmacol 1998; 54(5): 834–43

    PubMed  CAS  Google Scholar 

  81. Molina-Holgado F, Grencis R, Rothwell NJ. Interactions of cannabinoids and anti-inflammatory cytokines in astrocyte mice cultures. Soc Neurosci Abstr 1999; 25(1): 1180

    Google Scholar 

  82. Sanchez C, Galve-Roperh I, Canova C, et al. Delta-9-tetrahy-drocannabinol induces apoptosis in C6 glioma cells. FEBS Lett 1998; 436(1): 6–10

    PubMed  CAS  Google Scholar 

  83. Waksman Y, Olson JM, Carlisle SJ, et al. The central cannabinoid receptor (CB1) mediates inhibition of nitric oxide production by rat microglial cells. J Pharmacol Exp Ther 1999; 288(3): 1357–66

    PubMed  CAS  Google Scholar 

  84. Shohami E, Gallily R, Mechoulam R, et al. Cytokine production in the brain following closed head injury: dexanabinol (HU-211) is a novel TNF-alpha inhibitor and an effective neuroprotectant. J Neuroimmunol 1997; 72(2): 169–77

    PubMed  CAS  Google Scholar 

  85. Hunter SA, Audette CA, Burstein S. Elevation of brain prostaglandin E2 levels in rodents by delta 1-tetrahydrocannabinol. Prostaglandins Leukot Essent Fatty Acids 1991; 43(3): 185–90

    PubMed  CAS  Google Scholar 

  86. Di Marzo V, Fontana A, Cadas H, et al. Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature 1994; 372(6507): 686–91

    PubMed  Google Scholar 

  87. Deutsch DG, Chin SA. Enzymatic synthesis and degradation of anandamide, a cannabinoid receptor agonist. Biochem Pharmacol 1993; 46(5): 791–6

    PubMed  CAS  Google Scholar 

  88. De Petrocelli L, Melck D, Ueda N, et al. Novel inhibitors of brain, neuronal, and basophilic anandamide amidohydrolase. Biochem Biophys Res Commun 1997; 231: 82–88

    Google Scholar 

  89. Bisogno T, Berrendero F, Ambrosino G, et al. Brain regional distribution of endocannabinoids: implications for their biosynthesis and biological function. Biochem Biophys Res Commun 1999; 256: 377–80

    PubMed  CAS  Google Scholar 

  90. Merrill JE, Chen IS. HIV-1, macrophages, glial cells, and cytokines in AIDS nervous system disease. FASEB J 1991; 5(10): 2391–7

    PubMed  CAS  Google Scholar 

  91. Patterson PH. Cytokines in Alzheimer’s disease and multiple sclerosis. Curr Opin Neurobiol 1995; 5(5): 642–6

    PubMed  CAS  Google Scholar 

  92. Hayashi Y, Nomura M, Yamagishi S, et al. Induction of various blood-brain barrier properties in non-neural endothelial cells by close apposition to co-cultured astrocytes. Glia 1997; 19(1): 13–26

    PubMed  CAS  Google Scholar 

  93. Fabry Z, Raine CS, Hart MN. Nervous tissue as an immune compartment: the dialect of the immune response in the CNS. Immunol Today 1994; 15(5): 218–24

    PubMed  CAS  Google Scholar 

  94. Merrill JE, Benveniste EN. Cytokines in inflammatory brain lesions: helpful and harmful. Trends Neurosci 1996; 19(8): 331–8

    PubMed  CAS  Google Scholar 

  95. Bouaboula M, Bourrie B, Rinaldi-Carmona M, et al. Stimulation of cannabinoid receptor CB1 induces krox-24 expression in human astrocytoma cells. J Biol Chem 1995; 270(23): 13973–80

    PubMed  CAS  Google Scholar 

  96. Rinaldi-Carmona M, Barth F, Heaulme M, et al. SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett 1994; 350(2–3): 240–4

    PubMed  CAS  Google Scholar 

  97. Rothwell NJ, Hopkins SJ. Cytokines and the nervous system II: actions and mechanisms of action. Trends Neurosci 1995; 18(3): 130–6

    PubMed  CAS  Google Scholar 

  98. Rothwell N, Allan S, Toulmond S. The role of interleukin-1 in acute neurodegeneration and stroke: pathophysiological and therapeutic implications. J Clin Invest 1997; 100(11): 2648–52

    PubMed  CAS  Google Scholar 

  99. Aschner M. Immune and inflammatory responses in the CNS: modulation by astrocytes. Toxicol Lett 1998; 102–103: 283–7

    PubMed  Google Scholar 

  100. Raine CS, Bonetti B, Cannella B. Multiple sclerosis: expression of molecules of the tumor necrosis factor ligand and receptor families in relationship to the demyelinated plaque. Rev Neurol (Paris) 1998; 154(8–9): 577–85

    CAS  Google Scholar 

  101. Selmaj K, Walczak A, Mycko M, et al. Suppression of experimental autoimmune encephalomyelitis with a TNF binding protein (TNFbp) correlates with downregulation of VCAM-1/VLA-4. Eur J Immunol 1998; 28(6): 2035–44

    PubMed  CAS  Google Scholar 

  102. Hofman FM, Hinton DR, Johnson K, et al. Tumor necrosis factor identified in multiple sclerosis brain. J Exp Med 1989; 170(2): 607–12

    PubMed  CAS  Google Scholar 

  103. Navikas V, Matusevicius D, Soderstrom M. Increased interleukin-6 mRNA expression in blood and cerebrospinal fluid mononuclear cells in multiple sclerosis. J Neuroimmunol 1996; 64(1): 63–9

    PubMed  CAS  Google Scholar 

  104. Tilg H, Dinarello CA, Mier JW. IL-6 and APPs: anti-inflammatory and immunosuppressive mediators. Immunol Today 1997; 18(9): 428–32

    PubMed  CAS  Google Scholar 

  105. Benveniste EN, Tang LP, Law RM, et al. Differential regulation of astrocyte TNF-alpha expression by the cytokines TGF-beta, IL-6 and IL-10. Int JDev Neurosci 1995; 13(3–4): 341–9

    CAS  Google Scholar 

  106. Consroe P, Musty R, Rein J, et al. The perceived effects of smoked cannabis on patients with multiple sclerosis. Eur Neurol 1997; 38(1): 44–8

    PubMed  CAS  Google Scholar 

  107. Leker RR, Shohami E, Abramsky O, et al. Dexanabinol: a novel neuroprotective drug in experimental focal cerebral ischemia. J Neurol Sci 1999; 162(2): 114–9

    PubMed  CAS  Google Scholar 

  108. Biegon A. Neuroprotective activity of HU-211, a novel non-psychotropic synthetic cannabinoid. Ann NY Acad Sci 1995; 765: 314

    PubMed  CAS  Google Scholar 

  109. Westlake TM, Howlett AC, Bonner TI, et al. Cannabinoid receptor binding and messenger RNA expression in human brain: an in vitro receptor autoradiography and in situ hybridization histochemistry study of normal aged and Alzheimer’s brains. Neuroscience 1994; 63: 637–52

    PubMed  CAS  Google Scholar 

  110. Volicer L, Stelly M, Morris J, et al. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. Int J Geriatr Psychiatry 1997; 12: 913–9

    PubMed  CAS  Google Scholar 

  111. Berglund BA, Boring DL, Wilken GH, et al. Structural requirements for arachidonylethanolamide interaction with CB 1 and CB2 cannabinoid receptors: pharmacology of the carbonyl and ethanolamide groups. Prostaglandins Leukot Essent Fatty Acids 1998; 59: 111–8

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Francisco Molina-Holgado.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Molina-Holgado, E., Guaza, C., Borrell, J. et al. Effects of Cannabinoids on the Immune System and Central Nervous System. BioDrugs 12, 317–326 (1999). https://doi.org/10.2165/00063030-199912050-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00063030-199912050-00001

Keywords

Navigation