Advertisement

Marihuana and the Immune System

Chapter

Abstract

Marihuana has been shown to decrease host resistance to bacterial, protozoan, and viral infections in experimental animal models and in vitro systems. Recent immuno epidemiological studies suggest that marihuana may also influence the outcome of viral infections in humans. The main substance in marihuana that exerts these immuno depressive effects is its major psychoactive constituent Δ9-tetrahydrocannabinol (THC). This cannabinoid alters the function of an array of immune cells including lymphocytes, natural killer cells, and macrophages, thereby affecting their capacity to exert anti microbial activities. Two modes of action by which THC affects immune responsiveness have been proposed. At sites such as the lung that are subject to exposure to high concentrations of THC and other cannabinoids contained in marihuana smoke, THC may alter cellular membranes because of its highly lipophilic nature. In contrast, at sites distal to the lung, THC at relatively low concentrations may exert its suppressive effects on immune cells by interacting with cannabinoid receptors CB1 and CB2. No controlled longitudinal epidemiological studies have yet correlated the immunosuppressive effects of Cannabis smoke on the incidence of infections or viral disease in different segments of the population.

Keywords

Natural Killer Cell Longitudinal Epidemiological Study Noid Receptor Decrease Host Resistance Marihuana Smoke 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Dewey, W. L. (1986) Cannabinoid pharmacology. Parmcol. Rev. 38, 151–178.Google Scholar
  2. 2.
    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.PubMedCrossRefGoogle Scholar
  3. 3.
    Cushman, P. and Khurana, R. (1976) Marihuana and T lymphocyte rosettes. Clin. Pharmacol. Ther. 19, 310–317.PubMedGoogle Scholar
  4. 4.
    Klein, T. W., Newton, C., Widen, R., and Friedman, H. (1985) The effect of delta-9-tetrahydrocannabinol and 11-hydroxy-delta-9-tetrahydrocannabinol on T-lymphocyte and B-lymphocyte mitogen responses. J. Immunopharmacol. 7, 451–466.Google Scholar
  5. 5.
    Munson, A. E., Levy, J. A., Harris, L. S., and Dewey, W. L. (1976) Effects of delta-9-tetrahydrocannabinol on the immune system, in The Pharmacology of Marijuana ( Braude, M. C., and Szara, S., eds.) Raven, New York, pp. 187–197.Google Scholar
  6. 6.
    Baczynsky, W. O. T. and Zimmerman, A. M. (1983) Enhanced growth of Legionella pneumophila tetrahydrocannabinol-treated macrophages. Proc. Soc. Exp. Biol. Med. 199 (1), 65–67.Google Scholar
  7. 7.
    Klein, T. W., Newton, C., and Friedman, H. (1987) Inhibition of natural killer cell function by marijuana components. J. Toxicol. Environ. Health 20, 321–332.PubMedCrossRefGoogle Scholar
  8. 8.
    Lopez-Cepero, M., Friedman, M., Klein, T., and Friedman, H. (1986) Tetrahydrocannabinol-induced suppression of macrophage spreading and phagocyte activity in vitro. J. leuk. Biol. 39, 679–686.Google Scholar
  9. 9.
    Cabral, G. A. and Vasquez, R. (1991) Marijuana decrease macrophage antiviral and antitumor activities. Adv. Biosci. 80, 93–105.Google Scholar
  10. 10.
    Burnette-Curley, d., Marciano-Cabral, F., Fischer-Stenger, K., and Cabral, G. A. (1993) 0–9-tetrahydrocannabinol inhibits cell contact-dependent cytotoxicity of bacillus Calmétte-Guérin-activated macrophages. Int. J. Immunopharmacol. 15, 371–382.Google Scholar
  11. 11.
    Gross, G., Roussaki, A., Ikenberg, H., and Dress, N. (1991) Genital warts do not respond to systemic recombinant interferon alpha-2a treatment during cannabis consumption. Dermatol. 183, 203–207.Google Scholar
  12. 12.
    Tindall, B., Cooper, D. A., Donovan, B., Barnes, T., Philpot, C. R., Gold, J., and Penny, R. (1988) The Sydney AIDS Project: development of acquired immnodeficiency syndrome in a group of HIV seropositive homosexual men. Aust. N.Z. J. Med. 18 (1), 8–15.PubMedCrossRefGoogle Scholar
  13. 13.
    Morahan, P. S., Klykken, P. C., Smith, S. H., Harris, L. S., and Munson, A. E. (1979) Effects of cannabinoids on host resistance to Listeria monocytogenes and herpes simplex virus. Infect. Immun. 23, 670–674.PubMedGoogle Scholar
  14. 14.
    Mishkin, E. M. and Cabral, G. A. (1985) Delta-9-tetrahydrocannabinol decreases host resistance to herpes simplex virus type 2 vaginal infection in B6C3F1 mice. J. Gen. Virol. 66, 2539–2549.PubMedCrossRefGoogle Scholar
  15. 15.
    Cabral, G. A., Mishkin, E. M., Marciano-Cabral, F., Coleman, P., Harris, L., and Munson, A. E. (1986) Effect of delta-9-tetrahydrocannabinol on herpes simplex virus type 2 vaginal infection in the guinea pig. Proc. Soc. Exp. Biol. 182, 181–186.PubMedGoogle Scholar
  16. 16.
    Klykken, P. C., Smith, S. H., Ley, J. A., Razdan, R., and Munson, A. E. (1977) Immuno suppressive effects of 8.9-eposyhexandrocannabinol (EHHC). J. Pharmacol. Exp. Ter. 201, 573–579.Google Scholar
  17. 17.
    Smith, S. H., Harris, L. S., Uwaydah, L. M., and Munson, A. E. (1978) Structure-activity relationships of natural and synthetic cannabinoids in suppression of humoral and cell-mediated immunity. J. Pharmacol. Exp. Ther. 207, 165–170.PubMedGoogle Scholar
  18. 18.
    Specter, S. C., Lancz, G., Westrich, G., and Friedman, H. (1991) Delta-9-tetrahydrocannabinol augments murine retroviral induced immunosuppression and infection. Int. J. Immunopharmacology 13 (4), 411–417.CrossRefGoogle Scholar
  19. 19.
    Klein, T. W., Newton, C., Widen, R., and Friedman, H. (1993) Delta-9-tetrahydrocannabinol injection induces cytokine-mediated mortality of mice infected with Legionella pneumophila. J. Pharmacol. Exp. Ther. 267 (2), 635–640.Google Scholar
  20. 20.
    Rosenkrantz H. (1976) The immune response and marihuana, in Marihuana: Chemistry, Biochemistry & Cellular Effects. (Nahas G. G., Paton W. D. M., and Idanpaan-Heikkila J., eds.) Springer-Verlag, New York, p. 441.Google Scholar
  21. 21.
    Hembree, W. C., Nahas G., Zeidenberg, P. and Huang, H. F. S. (1979) Changes in human spermatozoa associated with high dose marihuana smoking, in Marihuana: Biological Effects, Analysis, Cellular Responses, Reproduction and Brain. ( Nahas G. G. and Paton W. D. M., eds.) Pergamon, New York, pp. 429–439.Google Scholar
  22. 22.
    Stevens, J. G. and Cook, M. L. (1971) Restriction of herpes simplex virus by macrophages. N analysis of the cell-virus integration. J. Exp. Med. 133, 19–38.Google Scholar
  23. 23.
    Selgrade, M. K. and Osborne, J. E. (1974) Role of macrophages in resistance to murine cytomegalovirus. Infect. Immun. 10, 1381–1390.Google Scholar
  24. 24.
    Morahan, P. S., Glasgow, L. A., Crane, J. L., Jr., and Kern, E. R. (1977) Comparison of antiviral and antitumor activity of activated macrophages. Cell Immunol. 28, 404–415.PubMedCrossRefGoogle Scholar
  25. 25.
    Cabral, G. A. and Vasquez, R. (1992) Delta-9-tetrahydrocannabinol suppresses macrophage extrinsic antiherpesvirus activity, in Cannabis: Physiopathology, Epidemiology, Detection ( Nahas, G. G. and Latour, C., eds.) CRC Press, Boca Raton, FL, pp. 137–153.Google Scholar
  26. 26.
    Arata, S., Klein, T. W., Newton, C., and Friedman, H. (1991) Tetrahydrocannabinol treatment suppresses growth restriction of Legionella pneumophila in murine macrophage cultures. Life Sci. 49, 473–479.PubMedCrossRefGoogle Scholar
  27. 27.
    Marciano-Cabral, F. (1988) Biology of Naegleria spp. Microbiol. Revs. 52, 114–133.Google Scholar
  28. 28.
    Wing, D. R., Leuschner, J. T. A., Brent, G. A., Harvey, D. J., and Paton, W. D. M. (1985) Quantification of in vivo membrane associated delta-9-tetrahydrocannabinol and its effects on membrane fluidity, in Proceedings of the 9th International Congress of Pharmacology 3rd Satellite Symposium on Cannabis ( Harvey, D. J., ed.) IRL Press, Oxford, UK pp. 411–418.Google Scholar
  29. 29.
    Carrasco, L. and Smith, A. E. (1976) Sodium ions and the shut-off of host cell protein synthesis by piconviruses. Nature (London) 264, 807–809.CrossRefGoogle Scholar
  30. 30.
    Garry, R. F., Bishop, J. M., Parker, S., Westbrook, K, Lewis, G., and Waite, M. R. E. (1979) Na+ and K+ concentrations and the regulation of protein synthesis in sindbis virus-infected chick cells. Virology 96, 108–120.PubMedCrossRefGoogle Scholar
  31. 31.
    Desoize, B., Leger C., and Nahas, G. G. (1979) Plasma membrane inhibition of macromolecular precursor transport by THC. Biochemical Pharmacology, 28, 1113–1118.PubMedCrossRefGoogle Scholar
  32. 32.
    Poddar, M. K., Mitra, G., and Ghosh, J. J. (1978) Delta-9-tetrahydrocannabinol-induced changes in brain ribosomes. Toxicol. Appl. Pharmacol. 46, 737–757.PubMedCrossRefGoogle Scholar
  33. 33.
    Nahas, G. G., Morishima, A., and Desoize, B. (1977) Effects of cannabinoids on macromolecular synthesis and replication of cultured lymphocytes. Fed. Proc. 36, 1748–1752.PubMedGoogle Scholar
  34. 34.
    Matsuda, L. A., Lolait, S. J1, Brownstein, M. J., Young, A. C., and Bonner, T. I. (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346, 561–556.PubMedCrossRefGoogle Scholar
  35. 35.
    Chakrabarti, A., Onaivi, E. S., and Chaudhuri, G. (1995) cloning and sequencing of a cDNA encoding the mouse brain-type cannabinoid receptor protein. DNA Seq.-J. Seq. Map 5, 385–388.Google Scholar
  36. 36.
    Gérard, C., Mollereau, C., Vassart, G., and Parmentier, M. (1990) Nucleotide sequence of a human cannabinoid receptor cDNA. Nucleic Acids Res. 18, 7142.PubMedCrossRefGoogle Scholar
  37. 37.
    Howlett, A. C., Qualy, J. M., and Khachchatrian, L. L. (1986) Involvement of Gi in the inhibition of adenylate cyclase by cannabimimetic drugs. Mol. Pharmacol. 29, 307–313.Google Scholar
  38. 38.
    Mackie, K. and Hille, B. (1992) Cannabinoids inhibit N-type calcium channels in neuroblastoma-glioma cells. Proc. Natl. Acad. Sci. USA 89, 3825–3829.PubMedCrossRefGoogle Scholar
  39. 39.
    Selley, D. E., Stark, S., and Childers, S. R. (1996) Cannabinoid receptor stimulation of [35S]GTPy S binding in rat brain membranes. Life Sci. 59, 659–668.PubMedCrossRefGoogle Scholar
  40. 40.
    Childers, S. R. and Deadwyler, S. A. (1996) Role of cyclic AMP in the actions of cannabinoid receptors. Biochem. Pharmacol. 52, 819–827.PubMedCrossRefGoogle Scholar
  41. 41.
    Kaminski, N. E., Abood, M. E., Kessler, E K., Martin, B. R., and Schatz, A. R. (1992) Identification of a functionally relevant cannabinoid receptor on mouse spleen cells that is involved in cannabinoid-mediated immune modulation. Mol. Pharmacol. 42, 736–742.PubMedGoogle Scholar
  42. 42.
    Bouaboula, M., Rinaldi, M., Carayon, P., Carillon, C., Delpech, B., Shire, D. Le Fur, G., and Casellas, P. (1993) Cannabinoid-receptor expression in human leukocytes. Eur. J. Biochem. 214, 173–180.PubMedCrossRefGoogle Scholar
  43. 43.
    Munro, S., Thomas, K. L., and Abu-Shaar, M. (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365, 61–65.PubMedCrossRefGoogle Scholar
  44. 44.
    Galiègue, S., Mary, S., Marchand, J., Dussossoy, D., Carrière, D., Carayon, P., Bouaboula, M., Shire, D., Le Fur, G., and Casellas, P. (1995) Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur. J. Biochem. 232, 54–61.PubMedCrossRefGoogle Scholar
  45. 45.
    Lynn, A. B. and Herkenham, M (1994) 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. 268, 1612–1623.PubMedGoogle Scholar
  46. 46.
    Dove-Pettit, D. A., Anders, D. L., Harrison, M. P., and Cabral, G. A. (1996) Cannabinoid receptor expression in immune cells. Adv. Exp. Med. Biol. 402, 119–129.CrossRefGoogle Scholar
  47. 47.
    Kaminski, N. E., Koh, W. S., Yang, K. H., Lee, M., and Kessler, F. K. (1994) Suppression of the humoral immune response by cannabinoids is partially mediated through inhibition of adenylate cyclase by a pertussis toxin-sensitive G-protein coupled mechanism. Biochem. Pharmacol. 48, 1899–1908.PubMedCrossRefGoogle Scholar
  48. 48.
    McCoy, K. L., Gainey, D., and Cabral, G. A. (1995) 49-Tetrahydrocannabinol modulates antigen processing by macrophages. J. Pharmacol. Exp. Ther. 273, 1216–1223.Google Scholar
  49. 49.
    Clements, D., Cabral, G. A., and McCoy, K. L. (1996) Delta-9-tetrahydrocannabinol selctively inhibits macrophage co-stimulatory activity and down-regulates heat-stable antigen expression. J. Pharmacol. Exp. Ther. 277, 1315–1321.PubMedGoogle Scholar
  50. 50.
    Felder, C. C., Joyce, K. E., Briley, E. M., Mansouri, J., Mackie, K., Blond, O., Lai, Y., Ma, A. L., and Mitchell, R. L. (1995) Comparison of the pharmacology and signal transduction of the human cannabinoid CBI and CB2 receptors. Mol. Parmcol. 48, 443–450.Google Scholar
  51. 51.
    Watzl, B., Scuderi, P., and Watson, R. R. (1991) Marijuana components stimulate human peripheral blood mononuclear cell secretion of interferon-gamma and suppress interleukin-1-alpha in vitro. Int. J. Immunopharmacol. 13, 1091–1097.CrossRefGoogle Scholar
  52. 52.
    Nakano, Y., Pross, S. H., and Friedman, H. (1992) Modulation of interleukin 2 activity by delta-9-tetrahydrocannabinol and stimulation with concanavalin A, phytohemagglutinin, or anti-CD3 antibody. Proc. Soc. Exp. Biol. Med. 20, 165–168.Google Scholar
  53. 53.
    Zheng, Z. M., Specter, S., and Friedman, H. (1992) Inhibition by delta-9-tetrahydrocannabinol of tumor necrosis factor alpha production by mouse and human macrophages. Int. J. Immunopharmacology 14, 1445–1452.CrossRefGoogle Scholar
  54. 54.
    Fisher-Stenger, K., Dove Pettit, D. A., and Cabral, G. A. (1993) A9Tetrahydrocannabinol inhibition of tumor necrosis factor-alpha: suppression of post-translational events. J. Pharmacol. Exp. Ther. 267, 1558–1565.Google Scholar
  55. 55.
    Houston, D. B. and Howlett, A. C. (1993) Solubilization of the cannabinoid receptor from rat brain and its functional interaction with guanine nucleotide-binding proteins. Mol. Pharmacol. 43, 17–22.PubMedGoogle Scholar
  56. 56.
    Howlett, A. C., Champion, T. M., Wilken, G. H., and Mechoulam, R. (1990) Stereochemical effects of 11OH-8-tetrahydrocannabinol-dimethylheptyl to inhibit adenylate cyclase and bind to the cannabinoid receptor. Neuropharmacology 29, 161–165.PubMedCrossRefGoogle Scholar
  57. 57.
    Facci, L., Dal Toso, R., Romanello, S., Buriani, A., Skaper, S. D., and Leon, A. (1995) Mast cells express a peripheral receptor with differential sensitivity to anandamide and palmitoylethanolamide. Proc. Natl. Acad. Sci. USA 92, 3376–3380.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

There are no affiliations available

Personalised recommendations