CBD for Rheumatoid Arthritis

The following is pulled directly from Katchan, David & Shoenfield’s 2016 review, “Autoimmunity Reviews Cannabinoids and Autoimmune Diseases: A Systematic Review.”

Katchan, V., David, P., & Shoenfeld, Y. (2016). Autoimmunity Reviews Cannabinoids and autoimmune diseases : A systematic review. Autoimmunity Reviews, 15(6), 513–528. https://doi.org/10.1016/j.autrev.2016.02.008


Rheumatoid Arthritis

Joint diseases, inflammatory and degenerative, all share a pathological feature which is the loss of articular cartilage. In osteoarthritis and rheumatoid arthritis (RA), there is an increased cartilage breakdown. It is induced by an increased production of inflammatory cytokines, particularly IL-1 and tumor necrosis factor (TNF) produced by the articular chondrocytes or cells of the synovium 1,2. The overall result is an increase in metalloproteinases (MMPs) particularly MMP-3 and MMP-13, which are responsible for cartilage destruction 2.

Cannabinoids were shown to have anti-inflammatory effects and re- duce to joint damage in animal models of arthritis 3–5. According to in vitro studies, cannabinoids reduce cytokine production by RA fibroblasts as well as the release of matrix metalloproteinases (MMPs) from fibroblast-like synovial cells 6,7. Cannabinoids have also shown to reduce interleukin 1 (IL-1) induced proteoglycan and collagen degradation in bovine cartilage, thus reducing cartilage extracellular matrix (ECM) breakdown 2,8

Similar results were obtained with a selective CB2R agonist (HU-308) in vitro. Pre-treatment with HU-308 inhibited IL-1β-induced proliferation of cultured RA fibroblast-like synoviocytes. The agonist also decreased the production of proinflammatory cytokines (IL-6 specifically) and of matrix metalloproteinases that are thought to be involved in cartilage erosion (MMP3 and MMP13). In another study non-psychoactive cannabinoid ajulemic acid (AJA) reduced MMP-1, MMP-3 and MMP-9 release from fibroblast like synovial cells stimulated with IL-1a and TNFa 7. In vivo, AJA has also been shown to reduce the severity of adjuvant-induced arthritis 4. When a novel synthetic cannabinoid acid, Hebrew University-320 (HU-320) was administered to a mouse model of arthritis, inhibition of mouse macrophages TNF production was observed. The authors also noticed reduction of reactive oxygen intermediates and suppression of the rise in serum TNF level following endotoxin challenge 2,3.

All these data suggests that cannabinoids have anti-inflammatory properties and should be considered as a treatment for inflammatory arthritis. There are no studies in humans up to date on the use of canna- binoids reducing inflammation in RA and further studies are needed to prove that 2.

There are however, studies which have shown that cannabinoids are efficient in the treatment of pain associated with RA. There is evidence that endocannabinoid system plays an important role in the peripheral regulation of nociception 9,10. CB1R present on nociceptor terminals may mediate the anti-nociceptive and anti-inflammatory actions of locally produced N-arachidonoyl ethanolamine through its inhibitory influence on the release of excitatory neuropeptides 2,10.

CB1R and CB2R are also expressed in the dorsal root ganglia, and their stimulation at this level also decreases nociceptive transmission 11,12. At the central level, the endocannabinoid system controls nociception through CB1R located at spinal and supraspinal levels 13. Pharmacological studies have suggested a peripheral endocannabinoid basal activity that modulates nociceptor activity in osteoarthritic joints 14. CB1R and CB2R mRNA and protein, were found in synovial biopsies deriving from total knee arthroplasty of advanced osteoarthritis and rheumatoid arthritis patients 15. Both, anandamide (AEA) and 2-arachidonoylglycerol (2-AG) were detected in the synovial fluid of these patients, but not in healthy volunteers, providing further evidence for a functional endocannabinoid system in osteoarthritic joints 15. Spinal cord levels of AEA, 2-AG and their synthesizing enzymes were also increased in the rat model of osteoarthritis 16. All these findings provide evidence for both peripheral and central adaptive changes involving the endocannabinoid system during osteoarthritis 2.

Studies on human models are scarce and contradictory. A recent review article on the effect of cannabinoid nabiximol on chronic pain in rheumatic diseases shows that there is a low-quality evidence suggesting that cannabinoids may be associated with improvements in pain and sleep quality in RA. Measures of morning pain at rest, sleep quality and a global disease activity score showed improvement, but measures of pain intensity were unchanged 17. However, Savitex (dronabiol) is sometimes used to reduce pain in inflammatory joint disease 2,18.




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