Cannabinoids in Models of Chronic Inflammatory Conditions

Cannabis sativa has been used as an anti-inflammatory plant for millennia. However until the elucidation of the chemistry of its constituents and the discovery of the endogenous cannabinoid system only a limited amount of research had been done on the effects of the plant or its constituents on inflammation. In the present overview we summarize our work on the effects of the non-psychotropic cannabidiol (CBD) and of a synthetic cannabidiol-derived acid (HU-320) in animal models of arthritis. Both compounds block progression of the disease, when administered after its onset. Cannabidiol was equally effective was administered i.p. or orally. Significant protection of the joints against severe damage was noted. In vitro cannabidiol reduced lymphocyte proliferation, and TNF-α formation and blocked zymosan-triggered production of reactive oxygen intermediates (ROI). Ex vivo lymph node cells from CBD-treated mice showed a decrease of collagen II-specific proliferation and IFN-γ production. A decreased release of TNF by knee synovial cells was also noted. A synthetic cannabidiol derivative, HU-320 also inhibited production of TNF and ROI by mouse macrophages in vitro and suppressed in vivo rise in serum TNF following endotoxin challenge. HU-320 showed no activity in a standard assay for THC-type psychotropic effects. These results suggest that CBD and HU-320 hold promise as potential novel anti-inflammatory agents.