Effect of Stereospecific Cannabinoids on the Immune System

  • A. M. Zimmerman
  • N. Titishov
  • R. Mechoulam
  • S. Zimmerman
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 288)


The major psychoactive cannabinoid found in marijuana is delta-1-tetrahydrocannabinol, designated delta-1-THC. This cannabinoid is but one of 62 cannabinoids that have been identified in the plant (1). In addition to the cannabinoids, 364 organic compounds have also been identified. Cannabinoids are defined as naturally occurring 21 carbon compounds of cannabis including analogues of these compounds and their metabolites (2,3). Delta-1-THC as well as other cannabinoids, e.g., cannabinol and cannabidiol affect growth, development and reproductive activity and a variety of cellular systems including the immune system (4–8).


Productive Phase Inductive Phase Natural Killer Cell Activity Immunosuppressive Activity Body Weight Ratio 
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  1. 1.
    C. E. Turner, Marijuana and cannabis: why the conflict, in: “Marijuana ’84: proceedings of the Oxford symposium on Cannabis,” D. J. Harvey, ed., IRL Press, Oxford (1985).Google Scholar
  2. 2.
    R. Mechoulam, Cannabinoid chemistry, in: “Marijuana: chemistry, pharmacology, metabolism and clinical effects,” M. Mechoulam, ed., Academic Press, New York (1973).Google Scholar
  3. 3.
    R. K. Razdan, Structural-activity relationships in cannabinoids, Pharm. Rev. 38:75 (1986).PubMedGoogle Scholar
  4. 4.
    G. G. Nahas and W. D. M. Paton, eds., “Marijuana biological effects,” Pergamon Press, Oxford (1979).Google Scholar
  5. 5.
    S. Agurell, W. L. Dewey, and R. E. Willette, eds., “The cannabinoids: chemical pharmacologic and therapeutic aspects,” Academic Press, Orlando (1984).Google Scholar
  6. 6.
    D. J. Harvey, ed., “Marijuana ’84: proceedings of the Oxford symposium on Cannabis,” IRL Press, Oxford (1985).Google Scholar
  7. 7.
    B. R. Martin, Cellular effects of cannabinoids, Pharmacological Reviews 38:45 (1986).PubMedGoogle Scholar
  8. 8.
    M. C. Braude and A. M. Zimmerman, eds., “Genetic and perinatal effects of abused substances,” Academic Press, Orlando (1987).Google Scholar
  9. 9.
    R. J. Lau, D. G. Tubergen, M. Barr, and E. F. Domino, Phytohemagglutinininduced lymphocyte transformation in humans receiving delta-9-tetrahydro-cannabinol, Science 192:805 (1976).PubMedCrossRefGoogle Scholar
  10. 10.
    G. S. Rachelefsky, G. Opelz, M. R. Michey. P. Lessin, M. Kinchi, M. J. Silverstein, and E. R. Stiehm, Intact humoral and cell-mediated immunity in chronic marijuana smoking, J. Allergy Clin. Immunol. 58:483 (1976).PubMedCrossRefGoogle Scholar
  11. 11.
    S. G. White, S. C. Brin, and B. W. Janicki, Mitogen-induced blastogenic responses of lymphocytes from marijuana smokers, Science 188:71 (1975).PubMedCrossRefGoogle Scholar
  12. 12.
    P. Cushman and R. Khurana, Marijuana and T-lymphocyte rosettes, Clin. Pharm. Therap. 19:310 (1976).PubMedGoogle Scholar
  13. 13.
    P. Cushman and R. Khurana, A controlled cycle of tetrahydrocannabinol smoking, Life Sci. 20:971 (1977).PubMedCrossRefGoogle Scholar
  14. 14.
    S. Gupta, M. H. Grieco, and P. Cushman, Impairment of rosette-forming T-lymphocytes in chronic marijuana smokers, New Eng. J. Med. 291:874 (1974).PubMedCrossRefGoogle Scholar
  15. 15.
    G. G. Nahas, N. Suciu-Foca, J. P. Armand, and A. Morishima, Inhibition of cellular mediated immunity in marijuana smokers, Science 183:419 (1974).PubMedCrossRefGoogle Scholar
  16. 16.
    S. Pross, T. Klein, C. Newton, and H. Friedman, Differential effects of marijuana components on proliferation of spleen, lymph node and thymus cells in vitro ,Int. J. Immunopharm. 9:363 (1987).CrossRefGoogle Scholar
  17. 17.
    G. G. Nahas, B. Desoize, J. P. Armand, J. Hsu, and A. Morishima, Natural cannabinoids: apparent depression of nucleic acid and protein synthesis in cultured human lymphocytes, in: “The pharmacology of marijuana,” M. C. Braude and S. Szara, eds., Raven Press, New York (1976).Google Scholar
  18. 18.
    G. G. Nahas, A. Morishima, and B. Desoize, Effects of cannabinoids on macromolecular synthesis and replication of cultured lymphocytes, Fed. Proc. 36:1748 (1977).PubMedGoogle Scholar
  19. 19.
    L. Schwatzfarb, M. Neddie, and M. Chavez-Chase, Dose-related inhibition of leukocyte migration by marijuana and delta-9-tetrahydrocannabinol in vitro ,J. Clin. Pharm. 14:35 (1974).Google Scholar
  20. 20.
    S. C. Specter, T. Klein, C. Newton, M. Mondragon, R. Widen, and H. Friedman, Marijuana effects on immunity: suppression of natural killer cell activity by delta-9-tetrahydrocannabinol, Int. J. Immunopharm. 8:741 (1986).CrossRefGoogle Scholar
  21. 21.
    A. E. Munson, J. A. Levy, L. S. Harria, and W. L. Dewey, Effects of delta-9-tetrahydrocannabinol on the immune system, in: “The pharmacology of marijuana,” M. C. Braude and S. Szara, eds., Raven Press, New York (1976).Google Scholar
  22. 22.
    H. Rosenkrantz, A. J. Miller, and H. J. Esber, Delta-9-tetrahydrocannabinol suppression of the primary immune response in rats, J. Toxicol. Envir. Health 1:119 (1975).CrossRefGoogle Scholar
  23. 23.
    H. Rosenkrantz, The immune response and marijuana, in: “Marijuana: chemistry, biochemistry and cellular effects,” G. G. Nahas, ed., Springer-Verlag, New York (1976).Google Scholar
  24. 24.
    S. S. Lefkowitz and C. Yang, Effects of delta-9-tetrahydrocannabinol on mouse spleens, Res. Commun. Chem. Path. Pharm. 11:659 (1975).PubMedGoogle Scholar
  25. 25.
    S. S. Lefkowitz, K. Klager, D. Nemeth, and M. Preuss, Immunosuppression of mice by delta-9-tetrahydrocannabinol, Res. Commun. Chem. Path. Pharm. 19:101 (1978).PubMedGoogle Scholar
  26. 26.
    Y. K. Luthra, H. J. Esber, D. M. Lariviere, and H. Rosenkrantz, Assessment of tolerance to immunosuppressive activity of delta-9-tetrahydrocannabinol in rats, J. Immunopharm. 2:245 (1980).CrossRefGoogle Scholar
  27. 27.
    S. H. Smith, L. S. Harris, I. M. Uwaydah, and A. E. Munson, Structure-activity relationships of natural and synthetic cannabinoids in suppression of humoral and cell-mediated immunity, J. Pharm. Exp. Therap. 207:165 (1978).Google Scholar
  28. 28.
    W. O. T. Baczynsky and A. M. Zimmerman, Effects of delta-9-tetrahydrocannabinol, cannabinol and cannabidiol on the immune system of mice. I. In vitro investigation of the primary and secondary immune response, Pharmacology 26:1 (1983a).PubMedCrossRefGoogle Scholar
  29. 29.
    S. Zimmerman, A. M. Zimmerman, I. L. Cameron, and H. L. Laurence, Delta-1-tetrahydrocannabinol, cannabidiol and cannabinol effects on the immune response of mice, Pharmcology 15:10 (1977).Google Scholar
  30. 30.
    C. R. Mc-Carthy, M. B. Cutting, G. A. Simmons, W. Pereira, R. Laguarda, and G. L. Huber, The effect of marijuana on the in vitro function of pulmonary alveolar macrophages, in: “The pharmacology of marijuana,” M. C. Braude and S. Szara, eds., Raven Press, New York (1976).Google Scholar
  31. 31.
    M. Friedman, M. Lopez-Cepero, T. Klein, and H. Friedman, Suppressive effects of delta-9-tetrahydrocannabinol in vitro on phagocytosis by murine macrophages (42332), Proc. Soc. Exp. Biol. Med. 182:225 (1986).PubMedGoogle Scholar
  32. 32.
    M. Lopez-Cepero, M. Friedman, T. Klein, and H. Friedman, Tetrahydro-cannabinol-induced suppression of macrophage spreading and phagocytic activity in vitro ,J. Leuk. Bid. 39:679 (1986).Google Scholar
  33. 33.
    T. Klein, C. A. Newton, R. Widen, and H. Friedman, The effects of delta-9-tetrahydrocannabinol and ll-hydroxy-delta-9-tetrahydrocannabinol on T-lymphocyte and B-lymphocyte mitogen responses, J. Immunopharm. 7:451 (1985).CrossRefGoogle Scholar
  34. 34.
    W. O. T. Baczynsky and A. M. Zimmerman, Effects of tetrahydrocannabinol, cannabinol and cannabidiol on the immune system splenocytes, Pharma cology 26:12 (1983b).Google Scholar
  35. 35.
    R. Mechoulam, J. J. Feigenbaum, N. Lander, M. Segal, T. U. C. Jarbe, A. J. Hiltunen, and P. Consroe, Enantiomeric cannabinoids: stereospecificity of psychotropic activity, Experientia 44:762 (1988).PubMedCrossRefGoogle Scholar
  36. 36.
    R. J. Fessenden and J. S. Fessenden, “Organic chemistry,” Second Edition, Willard Grant Press, Boston (1982).Google Scholar
  37. 37.
    N. Titishov, R. Mechoulam, and A. M. Zimmerman, Stereospecific effects of (-) and ( + )-7-hydroxy-delta-6-tetrahydrocannabinol-dimethylheptyl on the immune system of mice, Pharmacology 39:337 (1989).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • A. M. Zimmerman
    • 1
  • N. Titishov
    • 1
  • R. Mechoulam
    • 2
  • S. Zimmerman
    • 3
  1. 1.Department of ZoologyUniversity of TorontoTorontoCanada
  2. 2.Faculty of Medicine, Medical FacultyThe Hebrew University of JerusalemJerusalemIsrael
  3. 3.Division of Natural Science, Glendon CollegeYork UniversityTorontoCanada

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