CBD Reduced Joint Inflammation and Bone Damage in Rheumatoid Arthritis Model, Study Finds

Cannabidiol (CBD) reduced joint inflammation, abnormal blood vessel growth and bone destruction in a rat model of rheumatoid arthritis, according to a study published in the journal Phytomedicine.

Researchers from Hunan University of Chinese Medicine examined whether CBD could slow rheumatoid arthritis progression by limiting synovial angiogenesis, the formation of new blood vessels in the tissue lining the joints. This process can contribute to persistent inflammation and joint damage.

The researchers used rats with adjuvant-induced arthritis, treating them with CBD at doses of 5 or 10 milligrams per kilogram. CBD significantly reduced arthritis severity, inflammation, blood vessel formation in the joints and structural bone damage, based on arthritis scores, micro-CT imaging and tissue analyses.

Laboratory experiments also examined CBD’s effects on fibroblast-like synoviocytes, specialized cells that become abnormally active in rheumatoid arthritis. At concentrations that were not toxic to the cells, CBD reduced their proliferation, migration and invasion while decreasing the release of inflammatory signaling proteins.

The findings suggest that CBD acted partly by promoting the breakdown of hypoxia-inducible factor-1 alpha (HIF-1α), a protein that accumulates under low-oxygen conditions and can encourage inflammation and blood vessel formation. CBD appeared to increase the tagging of HIF-1α for destruction through the body’s ubiquitin-proteasome system.

This subsequently reduced the release of vascular endothelial growth factor A (VEGFA) and angiopoietin-2, two proteins involved in forming and maintaining blood vessels.

When researchers exposed human endothelial cells to conditioned material from CBD-treated rheumatoid arthritis cells, the endothelial cells showed reduced migration and a decreased ability to form capillary-like structures. The effect was attributed to changes in the signaling material released by the arthritis cells rather than CBD being transferred directly to the endothelial cells.

The researchers conclude by stating:

CBD attenuates RA pathogenesis not only by directly suppressing RA-FLS hyperactivity but also by severing the pro-angiogenic paracrine crosstalk between RA-FLS and endothelial cells. These effects are driven by the ubiquitin-proteasome-dependent degradation of HIF-1α in RA-FLS via direct structural engagement, which depletes VEGFA/ANG-2 production and subsequent endothelial VEGFR2 activation. These findings highlight CBD as a promising disease-modifying anti-angiogenic therapeutic agent for RA.