Cannabinoid Receptor Agonist May be Beneficial for Rheumatoid Arthritis

A treatment that targets the CB2 cannabinoid receptor may be an effective treatment for rheumatoid arthritis and synovitis, according to research published in BMC Musculoskeletal Disorders.

A collaborative team of researchers from the United Kingdom investigated cannabinoid receptor isoform CB2 as a target for treatment for rheumatoid arthritis while reviewing current treatments available to patients. The researchers noted synovitis is a central component of rheumatoid arthritis while also contributing to osteoarthritis. While pain symptoms can be treated in these diseases with medications like NSAIDs or paracetamol, control of rheumatic pain is particularly difficult. Breakout medications the researchers identified were sprifermin (human recombinant FGF-18) and tanezumab (anti-NFG monoclonal antibody).

Previous research has tested the 200-fold selective CB2 agonist JWH133 against both fibroblast-like synovial cell (FLS) inflammation and the murine collagen type II-induced arthritis model of rheumatoid arthritis and found what the authors termed “widespread and encouraging results.” Using in vitro models, FLS cultures from rheumatoid arthritis patients show that FLS produces IL-6, MMP-3, and CCL2 (also called MCP-1) when stimulated with TNF-a. The effectiveness of the CB2 agonist as a therapy was shown through its inhibition of CCL2. The CB2 agonist reduced histological indicators of joint degeneration, and JW133 inhibited markers of osteoclastogenesis, which are potential therapeutic targets in osteoarthritis. JWH133 could have implications for implications of bone loss in rheumatoid arthritis, too, the researchers commented.

Also, in rat models, CB2-deficient mice developed osteoporosis with age. JWH133 attenuated pain behaviors in the rats which researchers of a previous study termed an overall reduction in arthritic scores in collagen type II induced arthritis rats when compared to non CB2 deficient controls.

“Musculoskeletal biology has been in need of a selective CB2 agonist in arthritic models,” the investigators concluded. “The apparent beneficial effects reported here are comparatively mild, but could be synergistic to each other with benefits in terms of reduced pain, reduced inflammatory activity and reduced osteoclastogenesis of infiltrating macrophages.”

The researchers acknowledged that joint pharmacology is an area of study often overlooked by investigators, and developments in novel treatments are needed. Synovium contain sensory nerve endings and is a clear source of pain for both rheumatoid and osteoarthritis, although limited research time has been dedicated to the subject. Synovium is harder to access in rodent models, where many joint medications are piloted before human studies. The normal synovium is more easily isolated in humans and larger animals.