Figure 1

Cannabinoids have multiple actions in the synovium. The synovium is a richly vascularised and innervated tissue that becomes inflamed in both RA[12] and OA[13]. Fibroblast-like synovial cells (FLS) lie at the heart of synovial tissue; producing synovial fluid and mediating both pro- and anti-inflammatory properties of the synovium. A number of cytokines act on the FLS and induce release of further cytokines. The CB₂ receptor is expressed more in the RA synovium than that of the OA joint. Production of CCL2, MMP-3 and IL-6 were all suppressed by the selective CB₂ agonist JWH133 applied to in TNF-α stimulated FLS. Monocyte osteoclastogenesis was also suppressed. These factors are all important in arthritis. IL-6 mediates pain, MMP-3 mediates cartilage destruction and CCL-2 is a monocyte chemoattractant protein. Monocytes giving rise to osteoclasts (which re-absorb bone) and infiltrating macrophages that perpetuate inflammation. Action of cannabinoids will prove more complex however in complete joints, since CB₂ receptors interact with TRPV1 and have been reported to increase afferent nerve firing[14], and chondrocytes express both CB₁ and CB₂ under some conditions[15].