Examination of the immunosuppressive effect of delta9-tetrahydrocannabinol in streptozotocin-induced autoimmune diabetes

Int Immunopharmacol. 2001 Apr;1(4):699-712. doi: 10.1016/s1567-5769(01)00003-0.


delta9-Tetrahydrocannabinol (delta9-THC) is capable of modulating a variety of immune responses, but has not been evaluated in models of immune-based diabetes. The objectives of the present study were: (a) to investigate the effect of delta9-THC in an established model of multiple low dose streptozotocin (MLDSTZ)-induced autoimmune diabetes; and (b) to determine the contribution of the immune response in the MLDSTZ model. CD-1 mice were treated with 40 mg/kg STZ for 5 days in the presence or absence of delta9-THC treatment. delta9-THC administered orally in corn oil at 150 mg/kg for 11 days attenuated, in a transient manner, the MLDSTZ-induced elevation in serum glucose and loss of pancreatic insulin. MLDSTZ-induced insulitis and increases in IFN-gamma, TNFalpha and IL-12 mRNA expression were all reduced on Day 11 by co-administration of delta9-THC. In separate studies, six doses of delta9-THC, given after completion of STZ treatment, was found equally effective in attenuating mice from MLDSTZ-induced diabetes. Studies performed using B6C3F1 mice showed moderate hyperglycemia and a significant reduction in pancreatic insulin by MLDSTZ in the absence of insulitis. In addition, MLDSTZ produced a less pronounced hyperglycemia compared to CD-1 mice that was not attenuated by delta9-THC. These results suggest that MLDSTZ can initiate direct beta-cell damage, thereby augmenting the destruction of beta-cells by the immune system. Moreover, these results indicate that delta9-THC is capable of attenuating the severity of the autoimmune response in this experimental model of autoimmune diabetes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / prevention & control*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / pathology
  • CD3 Complex / analysis
  • Cytokines / genetics
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Experimental / prevention & control*
  • Dronabinol / pharmacology*
  • Immunosuppressive Agents / pharmacology*
  • Lymphocyte Activation / drug effects
  • Male
  • Mice
  • RNA, Messenger / analysis
  • Streptozocin


  • CD3 Complex
  • Cytokines
  • Immunosuppressive Agents
  • RNA, Messenger
  • Streptozocin
  • Dronabinol