title: The endocannabinoid system and its therapeutic implications in rheumatoid arthritis.
abstract: Since the discovery of the endogenous receptor for Δ(9)-tetrahydrocannabinol, a main constituent of marijuana, the endocannabinoid system (comprising cannabinoid receptors and their endogenous ligands, as well as the enzymes involved in their metabolic processes) has been implicated as having multiple regulatory functions in many central and peripheral conditions, including rheumatoid arthritis (RA). RA is an immune-mediated inflammatory disease that is associated with the involvement of many kinds of cells (such as fibroblastlike synoviocytes [FLSs], osteoclasts, T cells, B cells, and macrophages) and molecules (such as interleukin-1β, tumor necrosis factor-α, interleukin-6, matrix metalloproteinases [MMPs], and chemokines). Increasing evidence suggests that the endocannabinoid system, especially cannabinoid receptor 2 (CB2), has an important role in the pathophysiology of RA. Many members of the endocannabinoid system are reported to inhibit synovial inflammation, hyperplasia, and cartilage destruction in RA. In particular, specific activation of CB2 may relieve RA by inhibiting not only the production of autoantibodies, proinflammatory cytokines, and MMPs, but also bone erosion, immune response mediated by T cells, and the proliferation of FLSs. In this review, we will discuss the possible functions of the endocannabinoid system in the modulation of RA, which may be a potential target for treatment.
authors: Department of Pharmacy, Children's Hospital of Soochow University, Suzhou, China; Department of Rheumatology & Immunology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Huan
authors: H
authors: Gui
authors: Department of Rheumatology & Immunology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors: Qiang
authors: Q
authors: Tong
authors: Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, USA; Division of Pain Medicine, Mayo Clinic, Rochester, MN, USA.
authors: Wenchun
authors: W
authors: Qu
authors: Department of Pharmacy, Children's Hospital of Soochow University, Suzhou, China. Electronic address: maocm68@163.com.
authors: Chen-Mei
authors: CM
authors: Mao
authors: Department of Rheumatology & Immunology, Changhai Hospital, Second Military Medical University, Shanghai, China. Electronic address: dsm@medmail.com.cn.
authors: Sheng-Ming
authors: SM
authors: Dai
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002186:Cannabinoids / Q000008:administration & dosage / Q000627:therapeutic use*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D063388:Endocannabinoids / Q000276:immunology*; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology; D006801:Humans; D010006:Osteoblasts / Q000187:drug effects / Q000276:immunology; D043882:Receptors, Cannabinoid / Q000276:immunology*
chemical_list: D002186:Cannabinoids; D016207:Cytokines; D063388:Endocannabinoids; D043882:Receptors, Cannabinoid
keywords: Cannabinoid receptors; Drug therapy; Endocannabinoid system; Endocannabinoids; Rheumatoid arthritis