Cannabidiol lowers incidence of diabetes in non-obese diabetic mice.
Cannabidinoids are components of the Cannabis sativa (marijuana) plant that have been shown capable of suppressing inflammation and various aspects of cell-mediated immunity. Cannabidiol (CBD), a non-psychoactive cannabidinoid has been previously shown by us to suppress cell-mediated autoimmune joint destruction in an animal model of rheumatoid arthritis. We now report that CBD treatment significantly reduces the incidence of diabetes in NOD mice from an incidence of 86% in non-treated control mice to an incidence of 30% in CBD-treated mice. CBD treatment also resulted in the significant reduction of plasma levels of the pro-inflammatory cytokines, IFN-gamma and TNF-alpha. Th1-associated cytokine production of in vitro activated T-cells and peritoneal macrophages was also significantly reduced in CBD-treated mice, whereas production of the Th2-associated cytokines, IL-4 and IL-10, was increased when compared to untreated control mice. Histological examination of the pancreatic islets of CBD-treated mice revealed significantly reduced insulitis. Our results indicate that CBD can inhibit and delay destructive insulitis and inflammatory Th1-associated cytokine production in NOD mice resulting in a decreased incidence of diabetes possibly through an immunomodulatory mechanism shifting the immune response from Th1 to Th2 dominance.
Weiss
L
L
Hadassah University Hospital, Department of Bone Marrow Transplantation & Cancer Immunotherapy, POB 12000, Jerusalem, 91120, Israel.
Zeira
M
M
Reich
S
S
Har-Noy
M
M
Mechoulam
R
R
Slavin
S
S
Gallily
R
R
D000818:Animals; D002185:Cannabidiol / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D002185:Cannabidiol; D007371:Interferon-gamma