Influence of Marijuana Components (THC and CBD) on Human Mononuclear Cell Cytokine Secretion In vitro

Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 288)


Cytokines are a class of polypeptides produced by cells of the immune system. They coordinate the immune response to an antigenic challenge and play key roles in immunomodulation and host defense (1,2), and exert also metabolic effects (3,4). Therefore, a change in cytokine secretion caused by drugs of abuse could have an impact on immunological systems and metabolism. Delta-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, has been shown to modulate virus and mitogen induced cytokine secretion in mice. Intraperitoneal administered THC (5-100 mg/kg) decreased the plasma concentration of alpha-/beta-interferon (IFN) significantly (5). Chronic in vivo exposure of mice to THC (50 mg/kg for 56 days) also reduced the secretion of alpha-/beta-IFN in cultured, mitogen-stimulated spleen cells (6). In vitro culture of murine spleen cells together with THC (2.5–10 M-g/ml) showed dose-dependent responses in the alpha-/beta-IFN secretion. Low concentrations had no effect on alpha-/beta-IFN secretion, while 5 to 10 yg/ml were significantly suppressive (6). However, all these immunomodulatory concentrations were high and well above the pharmacological range of 1-100 ng/ml of THC found in the plasma of human marijuana smokers (7). Friedman et al., also investigated the effect of THC on the secretion of different cytokines by cultured murine spleen cells using bioassays (8). Only concentrations above the pharmacological range were used (5–10 μg/ml). All suppressed in a dose-dependent manner the secretion of cytokines. Lipopolysaccharide (LPS)-induced secretion of IFN (alpha-/beta) in splenocytes, adherent and nonadherent cells was reduced to 85%, a reduction was also observed by chronic administration of THC to these cells.


Cytokine Secretion Natural Killer Cell Activity Human PBMC Ethyl Alcohol Solution Tumor Necrosis Factor Release 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    S. B. Mizel, The interleukins, FASEB J. 3:2379 (1989).PubMedGoogle Scholar
  2. 2.
    F. R. Balkwill, and R. Burke, The cytokine network, Immun. Today 10:299 (1989).PubMedCrossRefGoogle Scholar
  3. 3.
    R. F. Grimble, Cytokines: Their relevance to nutrition, Europ. J. Clin. Nutr. 43:217 (1989).Google Scholar
  4. 4.
    K. C. Klasing, Nutritional aspects of leukocytic cytokines, Amer. J. Clin. Nutr. 14 36 (1988).Google Scholar
  5. 5.
    G. A. Cabral, J. C. Lockmuller, and E. M. Mishkin, Delta-9-tetrahydrocannabinol decreases alpha-beta interferon response to herpes simplex virus type 2 in the B6C3F1 mouse, Proc. Soc. Exp. Biol. Med. 181:305 (1986).PubMedGoogle Scholar
  6. 6.
    D. K. Blanchard, C. Newton, T. W. Klein, W. E. Stewart II, and H. Friedman, In vitro and in vivo suppressive effects of delta-9-tetrahydrocannabinol in interferon production by murine spleen cells, Int. J. Immunopharmac. 8:819 (1986).CrossRefGoogle Scholar
  7. 7.
    S. Agurell, M. Halldin, J. E. Lindgren, A. Ohlsson, M. Widman, H. Gillespie, and L. Hollister, Pharmacokinetics and metabolism of delta-1-tetrahydrocannabinol and other cannabinoids with emphasis on man, Pharmacol. Reviews 38:21 (1986).Google Scholar
  8. 8.
    H. Friedman, T. Klein, S. Specter, S. Pross, C. Newton, D. K. Blanchard, and R. Widen, Drugs of abuse and virus susceptibility, Adv. Biochem. Psycho-pharm. 44:125 (1988).Google Scholar
  9. 9.
    A. E. Munson, and K. O. Fehr, in: “Adverse Health and Behavioral Consequences of Cannabis Use,” K. O. Fehr and H. Kalant, ed., Addiction Research Foundation, Toronto (1983).Google Scholar
  10. 10.
    M. D. Yahya, R. and R. Watson, Immunomodulation by morphine and marijuana, Life Sciences 41:2503 (1987).PubMedCrossRefGoogle Scholar
  11. 11.
    L. E. Hollister, Marijuana and immunity, J. Psychoactive Drugs 20:3 (1988).PubMedGoogle Scholar
  12. 12.
    S. C. Specter, T. W. Klein, C. Newton, M. Mondragon, R. Widen, and H. Friedman, Marijuana effects on immunity: Suppression of human natural killer cell activity by delta-9-tetrahydrocannabinol, Int. J. Immunopharmac. 8:741 (1986).CrossRefGoogle Scholar
  13. 13.
    T. W. Klein, C. Newton, and H. Friedman, Inhibition of natural killer cell function by marijuana components, J. Toxicol. Environ. Health 20:321 (1987).PubMedCrossRefGoogle Scholar
  14. 14.
    S. Specter, M. Rivenbark, C. Newton, Y. Kawakami, and G. Lancz, Prevention and reversal of delta-9-tetrahydrocannabinol induced depression of natural killer cell activity by interleukin-2, Int. J. Immunopharmac. 11:63 (1989).CrossRefGoogle Scholar
  15. 15.
    C. E. Turner, Marijuana and cannabis: Research why the conflict? in: “Marijuana ’84,” D. Y. Harvey, ed., IRL Press, Oxford (1985).Google Scholar
  16. 16.
    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, Pharmacology 15:10 (1977).PubMedCrossRefGoogle Scholar
  17. 17.
    Y. D. Luo, M. L. Shen, and D. E. Ou, Does delta-9-tetrahydrocannabinol suppress human immune functions? FASEB J. 3:Abstr. 291 (1989).Google Scholar
  18. 18.
    F. Lu and D. W. Ou, Cocaine or delta-9-tetrahydrocannabinol does not affect cellular cytotoxicity in vitro ,Int J. Immunopharmac. 11:849 (1989).CrossRefGoogle Scholar
  19. 19.
    S. Burstein, S. A. Hunter, K. Ozman, and L. Renzulli, Cannabinoid-induced elevation of lipoxygenase products in mouse peritoneal macrophages, Biochem. Pharmacol. 33:2653 (1984).PubMedCrossRefGoogle Scholar
  20. 20.
    V. Patel, M. Borysenko, M. S. A. Kumar, and W. J. Millard, Effects of acute and subchronic delta-9-tetrahydrocannabinol administration on the plasma catecholamine, beta-endorphin, and corticosterone levels and splenic natural killer cell activity in rats, Proc. Soc. Exp. Biol. Med. 180:400 (1985).PubMedGoogle Scholar
  21. 21.
    W. A. Devane, F. A. Dysarz III, M. R. Johnson, L. S. Melvin, and A. C. Howelett, Determination and characterization of a cannabinoid receptor in rat brain, Mol. Pharmacol. 34:605 (1988).PubMedGoogle Scholar
  22. 22.
    B. R. Martin, Cellular effects of cannabinoids, Pharmacol. Reviews 38:45 (1986).Google Scholar
  23. 23.
    S. Endres, J. G. Cannon, R. Ghorbain, R. A. Dempsey, S. D. Sisson, G. Lonnemann, J. W. D. Van der Meer, S. M. Wolff, and D. A. Dinarello, In vitro production of IL-1 beta, IL-1 alpha, TNF and IL-2 in healthy subjects: distribution, effect of cyclooxygenase inhibition and evidence of independent gene regulation, Eur. J. Immunol. 19:2327 (1989).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  1. 1.Department of Family and Community Medicine, Arizona Health Sciences CenterUniversity of ArizonaTucsonUSA
  2. 2.Department of Microbiology and Immunology Arizona Cancer CenterUniversity of ArizonaTucsonUSA

Personalised recommendations