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Marijuana, Receptors and Immunomodulation

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The Brain Immune Axis and Substance Abuse

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 373))

Abstract

It is now widely accepted that drugs of abuse, such as opiates, cocaine and marijuana, as well as other abuse drugs, both recreational and psychoactive, are potent immunomodulators, suppressing and sometimes enhancing the immune response. A wide variety of models have been used both in vivo and in vitro to demonstrate the immunomodulatory properties of such drugs and the mechanisms involved (Bacynsky et al., 1983a, b, Cushman, and Khurana, 1976, Friedman et al., 1991, 1994, Hollister, 1988, Petersen, 1976, Zimmerman, et al., 1977). In recent years it has been shown in various studies that morphine, cocaine, marijuana and also alcohol have marked effects on various parameters of immunity, including those mediated by T cells, i.e., cell mediated immunity, B cells, i.e., humoral immunity such as antibody formation, as well as natural killer cells, macrophages and PMN cell mediated killing of microbes like bacteria, viruses and fungi. For example, recent studies in this laboratory have shown that marijuana and its components are markedly immunomodulatory (Blanchard et al., 1986, Djeu et al., 1991, Kawakami, 1988 a, b, Klein et al., 1985, 1987, 1993, 1994, Lopez-Cepero, et al., 1986, Pross et al., 1990, 1992, Shivers et al., 1994, Zhu et al., 1993, 1994).

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References

  • Baczynsky, W.O.T. and Zimmerman, A.M. Effects of Δ9-tetrahydrocannabinol, cannabinol, and cannabidiol on the immune system in mice: I. In vivo investigation of the primary and secondary immune response. Pharmacology 26: 1–11, 1983.

    Article  PubMed  CAS  Google Scholar 

  • Baczynsky, W.O.T. and Zimmerman, A.M. Effects of Δ9-tetrahydrocannabinol, cannabinol, and cannabidiol on the immune system in mice: II. In vitro investigation using cultured mouse splenocytes. Pharmacology 26: 12–19, 1983.

    Article  PubMed  CAS  Google Scholar 

  • Blanchard, D.K., Newton, C., Klein, T.W., Stewart, W.E., II, and Friedman, H. In vitro and in vivo suppressive effects of delta-9-tetrahydrocannabinol on interferon production by murine spleen cells. Int. J. Immunopharmac. 8: 819–824, 1986.

    Article  CAS  Google Scholar 

  • Bradley, S.G., Munson, A.E., Dewey, W.L., and Harris, L.S. Enhanced susceptibility of mice to combinations of Δ9-tetrahydrocannabinol and live or gilled gram-negative bacteria. Infect. Immun. 17: 325–329, 1977.

    PubMed  CAS  Google Scholar 

  • Bouaboula, M., Rinaldi, M., Carayon, P., Carillon, C., Delpech, B., Shire, D., Le Fur, G., Casellas, P. Cannabinoid-receptor expression in human leukocytes. Eur. J. Biochem. 214: 173–180, 1993.

    Article  PubMed  CAS  Google Scholar 

  • Burnette-Curley, D., Marciano-Cabral, F., Fischer-Stenger, K., and Cabral, G.A. Delta-9-tetrahydrocannabinol inhibits cell contact-dependent cytotoxicity of Bacillus Calmette-Guerin-activated macrophages. Int. J. Immunopharmac. 15: 371–382, 1993.

    Article  CAS  Google Scholar 

  • Cabral, G.A., Lockmuller, J.C., and Mishkin, E. M. Δ9-tetrahydroccanbinol decreases alpha/beta interferon response to Herpes simplex virus type 2 in the B6C3F1 mouse. Proc. Soc. Exp. Biol. Med. 181: 305–311, 1986.

    PubMed  CAS  Google Scholar 

  • Cabral, G.A., McNemey, P.J., and Mishkin, E.M. Δ9-tetrahydrocannabinol inhibits the splenocyte proliferative response to Herpes simplex virus type 2. Immunopharmac. Immunotoxicol. 9: 361–370, 1987.

    Article  CAS  Google Scholar 

  • Cabral, G.A., Mishkin, E.M., Marciano-Cabral, F., Coleman, P., Harris, L., Munson, A.E. Effect of Δ9-tetrahydrocannabinol on Herpes simplex virus type 2 vaginal infection in the guinea pig. Proc. Soc. Exp. Biol. Med. 182: 181–186, 1986.

    PubMed  CAS  Google Scholar 

  • Cabral, G.A. and Vasquez, R. Δ9-tetrahydrocannabinol suppresses macrophage extrinsic antiherpesvirus activity. Proc. Soc. Exp. Biol. Med. 199: 255–263, 1992.

    PubMed  CAS  Google Scholar 

  • Cushman, P., and Khurana, R. Marijuana and T lymphocyte rosettes. Clin. Pharmacol. Ther. 19: 310–317, 1976.

    PubMed  CAS  Google Scholar 

  • Devane, W.A., Dysarz, F.A., III, Johnson, M.R., Melvin, L.S., and Howlett, A.C. Determination and characterization of a cannabinoid receptor in rat brain. Molec. Pharm. 34: 605–613, 1988.

    PubMed  CAS  Google Scholar 

  • Diaz, S., Specter, S., and Coffey, R.G. Suppression of lymphocyte andenosine 3’:5’-cyclic monophosphate (cAMP) by delta-9-tetrahydrocannabinol. Int. J. Immunopharmac. 15: 523–532, 1993.

    Article  CAS  Google Scholar 

  • Djeu, J.Y., Wand, M., and Friedman, H., Adverse effect of Δ9-tetrahydrocannabinol on human neutrophil function. In: Friedman, H., Specter, S., and Klein, T.W. (eds.), Drug of Abuse, Immunity, and Immunodeficiency, pp. 57–62, Plenum Press, New York, 1991.

    Chapter  Google Scholar 

  • Donald, P.J. Advanced malignancy in the young marijuana smoker. In: Friedman,H., Specter, S., and Klein, T. W. (eds.), Drug of Abuse, Immunity, and Immunodeficiency, pp. 33–46, Plenum Press, New York, 1991.

    Chapter  Google Scholar 

  • Endicott, J.N., Skipper, P. and Hernandez, L. Marijuana and head and neck cancer. In: Friedman, H., Specter S., and Klein, T. W. (eds.), Drug of Abuse, Immunity and Immunodeficiency, pp. 107–112, Plenum Press, New York, 1991.

    Google Scholar 

  • Felder, C.C., Veluz, J.S., Williams, H.L., Briley, E.M., and Matsuda, L.A. Cannabinoid agonists stimulate both receptor-and nonreceptor-mediated signal transduction pathways in cells transfected with an expressing cannabinoid receptor clones. Molec. Pharm. 42: 838–845, 1992.

    PubMed  CAS  Google Scholar 

  • Fischer-Stenger, K., Pettit, D. A. D., and Cabral, G.A., Δ9-tetrahydrocanna binol inhibition of tumor necrosis factor-a: Suppression of post-translational events. J. Pharmacol. Exp. Ther. 267:1558–1565, 1993.

    PubMed  CAS  Google Scholar 

  • Friedman, H., Klein, T., and Specter, S. Immunosuppression by marijuana and components. In: Ader, R., Felten, D.L., and Cohen, N. (eds.) Psychoneuroimmunology, pp. 931–953, Academic Press, Inc., New York, 1991.

    Google Scholar 

  • Friedman, H., Shivers, S.C., and Klein, T.W. Drugs of abuse and the immune system. In: Dean, J.H., Luster, M.I., Munson, A.E., and Kimber I. (eds.) Immunotoxicology and Immunopharmacology, pp. 303–322, Raven Press, New York, 1994.

    Google Scholar 

  • Gérard, C.M., Mollereau, C., Vassart, G., and Parmentier, M. Molecular cloning of a human cannabinoid receptor. Biochem. J. 279: 129–134, 1991.

    PubMed  Google Scholar 

  • Gupta, S., Grieco, M. H., and Cushman, P., Jr. Impairment of rosette-forming T lymphocytes in chronic marihuana smokers. N. Engl. J. Med. 291: 874–876, 1974.

    Article  PubMed  CAS  Google Scholar 

  • Hollister, L.E. Marijuana and immunity. J. Psychoact. Drugs 20: 3–8, 1988.

    Article  CAS  Google Scholar 

  • Howlett, A.C., Johnson, M.R., Melvin, L.S., and Milne, G.M. Nonclassical cannabinoid analgetics inhibit adenylate cyclase: Development of a cannabinoid receptor model. Molec. Pharm. 33: 297–302, 1988.

    PubMed  CAS  Google Scholar 

  • Kaminski, N.E., Abood, M.E., Kessler, F.K., Martin, B.R., and Schatz, A.R. Identification of a functionally relevant cannabinoid receptor on mouse spleen cells that is involved in cannbinoid-mediated immune modulation. Molec. Pharm. 42: 736–742, 1992.

    PubMed  CAS  Google Scholar 

  • Kawakami, Y., Klein, T.W., Newton, C., Djeu, J., Dennert, G., Specter, S. and Friedman, H. Suppression by cannabinoids of a cloned cell line with natural killer cell activity. Proc. Soc. Exp. Biol. Med. 187: 355–359, 1988.

    PubMed  CAS  Google Scholar 

  • Kawakami, Y., Klein, T.W., Newton, C., Djeu, J., specter, S. and Friedman, H. Suppression by Δ9-tetrahydrocannabinol of interleukin 2-induced lymphocyte proliferation and lymphokine-activated killer cell activity. Int. J. Immunopharmac. 10: 485–488, 1988.

    Article  CAS  Google Scholar 

  • Klein, T.W. and Friedman, H., Modulation of murine immune cell function by marijuana components. In: Watson, R.R. (ed) Drugs of Abuse and Immune Function, pp. 87–111, CRC Press, Boca Raton, FL, 1990.

    Google Scholar 

  • Klein, T.W., Newton, C. and Friedman, H. Inhibition of natural killer cell function by marijuana components, J. Toxicol. Envir. Health 20: 321–332, 1987.

    Article  CAS  Google Scholar 

  • Klein, T.W., Newton, C., and Friedman, H. Resistance to Legionella pneumophila suppressed by the marijuana component, tetrahydrocannabinol. J. Infect. Dis. 169: 1177–1179, 1994.

    Article  PubMed  CAS  Google Scholar 

  • Klein, T.W., Newton, C., Widen, R. and Friedman, H. The effect of delta-9-tetrahydrocannabinol and 11-hydroxy-delta-9-tetrahydrocannabinol on T-lymphocyte and B-lymphocyte mitogen responses. J. Immunopharmac. 7: 451–466, 1985.

    Article  CAS  Google Scholar 

  • Klein, T.W., Newton, C., Widen, R. and Friedman, H. Δ9-tetrahydrocannabinol injection induces cytokine-mediated mortality of mice infected with Legionella pneumophila. J. Pharmacol. Exp. Ther. 267: 635–640, 1993.

    PubMed  CAS  Google Scholar 

  • Lancz, G., Specter, S. and Brown, H.K. Suppressive effect of Δ9-tetrandyrocannabinol on Herpes simplex virus infectivity in vitro. Proc. Soc. Exp. Biol. Med. 196: 401–404, 1991.

    PubMed  CAS  Google Scholar 

  • Lopez-Cepero, M., Friedman, M., Klein, T., and Friedman, H. Tetrahydrocannabinol induced suppression of macrophages spreading and phagocytic activity in vitro. J. Leukoc. Biol. 39: 679–686, 1986.

    PubMed  CAS  Google Scholar 

  • Lou, Y.D., Patel, M.K., Widerhold, M.D., and Ou, D.W. Effects of cannabinoids and cocaine on the mitogeninduced transformations of lymphocytes of human and mouse origins. Int. J. Immunopharmac. 14: 49–56, 1992.

    Article  Google Scholar 

  • Lyman, W.D., Sonett, J.R., Brosnan, C.F., Elkin, R., and Bornstein, M.B. Δ9-tetrahydrocannabinol: a novel treatment for experimental autoimmune encephalomylitis. J. Neuroimmunol. 23: 73–81, 1989.

    Article  PubMed  CAS  Google Scholar 

  • Matsuda, L.A., Lolait, S. J., Brownstein, M. J., Young, A.C., and Bonner, T. I. Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346: 561–564, 1990.

    Article  PubMed  CAS  Google Scholar 

  • Mishkin, E.M. and Cabral, G.A. Δ9-tetrahydrocannabinol decrease host resistance to Herpes simplex virus type 2 vaginal infection in the B6C3F1 mouse. J. Gen. Virol. 66: 2539–2549, 1985.

    Article  PubMed  CAS  Google Scholar 

  • Morahan, P.S., Klykken, P.C., Smith, S. H., Harris, L.S. and Munson, A.E. Effects of cannabinoids on host resistance to Listeria monocytogenes and Herpes simplex virus. Infect. Immun. 23: 670–674, 1979.

    PubMed  CAS  Google Scholar 

  • Munro, S., Thomas, K.L. and Abu-Shaar, M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 365: 61–65, 1993.

    Article  PubMed  CAS  Google Scholar 

  • Nahas, G. G., Morishima, A., and Desoize, B. Effects of cannabinoids on macromolecular synthesis and replication of cultured lymphocytes, Fed. Proc. 36: 1748–1752, 1977.

    PubMed  CAS  Google Scholar 

  • Nahas, G. G., Suciu-Foca, N., Armand, J-P., and Morishima, A. Inhibition of cellular mediated immunity in marihuana smokers. Science 183: 419–420, 1974.

    Article  PubMed  CAS  Google Scholar 

  • Petersen, B.H., Graham, J., and Lemberger, L. Marihuana, tetrahydrocannabinol, and T-cell function. Life Sci. 19: 395–400, 1976.

    Article  PubMed  CAS  Google Scholar 

  • Pross, S.H., Klein, T. W., Newton, C.A., Smith, J., Widen, R., and Friedman, H., Differential suppression of T-cell subpopulations by THC (Δ9-tetrahydrocannabinol). Int. J. Immunopharmac. 12: 539–544, 1990.

    Article  CAS  Google Scholar 

  • Pross, S.H., Nakano, Y., Widen, R., McHugh, S., Newton, C., Klein, T.W. and Friedman, H. Differing effects of Δ9-tetrahydrocannabinol (THC) on murine spleen cell populations dependent upon stimulators. Int. J. Immunopharmac. 14: 1019–1027, 1992.

    Article  CAS  Google Scholar 

  • Sherman, M.P., Roth, M.D., Gong, H. and Tashkin, D.P. Marijuana smoking, pulmonary function, and lung macrophage oxidant release. Pharmacol. Biochem. Beh. 40: 663–669, 1991.

    Article  CAS  Google Scholar 

  • Shivers, S. C., Newton, C., Friedman, H., and Klein, T.W. Δ9-tetrahydrocannabinol (THC) modulates IL-1 bioactivity in human monocyte-macrophage cell lines. Life Sci. 54: 1281–1289, 1994.

    Article  PubMed  CAS  Google Scholar 

  • Specter, S., Lancz, G., and Hazelden, J. Marijuana and immunity: Tetrahydrocannabinol mediated inhibition of lymphocyte blastogenesis. Int. J. Immunopharmac. 12: 261–267, 1990.

    Article  CAS  Google Scholar 

  • Specter, S., Lancz, G., Westrich, G., and Friedman, H. Δ9-tetrahydrocannabinol augments murine retroviral induced immunosuppression and infection. Int. J. Immunopharmac. 13: 411, 417, 1991.

    Article  CAS  Google Scholar 

  • Wallace, J. M., Tashkin, D.P. Oishi, J.S. and Barbers, R.G. Peripheral blood lymphocyte subpopulations and mitogen responsiveness in tobacco and marijuana smokers. J. Psychoact. Drugs 20: 9–14, 1988.

    Article  CAS  Google Scholar 

  • White, S.C., Brin, S.C., and Janicki, B.W. Mitogen-induced blastogenic responses of lymphocytes from marihuana smokers. Science 188: 71–72, 1975.

    Article  PubMed  CAS  Google Scholar 

  • Zheng, Z-M., Specter, S., and Friedman, H. Inhibition by delta-9-tetrahydrocannabinol of tumor necrosis factor alpha production by mouse and human macrophages. Int. J. Immunopharmac. 14: 1445–1452, 1992.

    Article  CAS  Google Scholar 

  • Zhu, W., Newton, C., Daaka, Y., Friedman, H., and Klein, T.W. Δ9-tetrandyrocannabinol (THC) enhances the secretion of interleukin 1 (ILI) from endotoxin stimulated macrophages. J. Pharm. Exp. Then (in press), 1994.

    Google Scholar 

  • Zhu, W., Igarashi, T., Qi, Z. T., Newton, C., Widen, R.E., Friedman, H. and Klein, T.W. Δ9-tetrahydrocannabinol (THC) decreases the number of high and intermediate affinity IL-2 receptors of the IL-2 dependent cell line NKB61A2. Int. J. Immunopharmac. 15: 401–408, 1993.

    Article  CAS  Google Scholar 

  • Zimmerman, S., Zimmerman, A.M., Cameron, I.L. and Laurence, H.L. Δ1-tetrahydrocannabinol, cannabidiol and cannabinol effects on the immune response of mice. Pharmacol. 15: 10–23, 1977.

    Article  CAS  Google Scholar 

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Friedman, H., Klein, T.W., Newton, C., Daaka, Y. (1995). Marijuana, Receptors and Immunomodulation. In: Sharp, B.M., Eisenstein, T.K., Madden, J.J., Friedman, H. (eds) The Brain Immune Axis and Substance Abuse. Advances in Experimental Medicine and Biology, vol 373. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1951-5_15

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  • DOI: https://doi.org/10.1007/978-1-4615-1951-5_15

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