Arthritis is a group of multiple diseases characterised by abnormalities in the musculoskeletal system, most commonly affecting the joints. In Australia, arthritis is the leading cause of chronic pain and disability. There is currently no cure of arthritis and many common medications provide symptomatic relief, as opposed to treating the disease itself. Roughly 95% of cases of arthritis fall under either Rheumatoid Arthritis (RA) or osteoarthritis.
RA is an autoimmune disease characterised by inflammation of the joints. Like all autoimmune diseases, antibodies and immune cells are overexpressed, particularly in the synovial cavity. RA is characterised by synovial hyperplasia in which there are too many cells in the synovial cavity, hence the area becomes inflamed. The painful inflammatory symptoms of RA are caused by an overactive immune response. Cannabinoids have been shown to produce analgesia to treat RA symptomatically. Additionally, CBD is a potent anti-inflammatory and evidence suggests that it may be helpful in relieving the underlying problem.
This image is a simplification for website aesthetics only. For more information please refer to the clinical studies referenced below.
Possible Benefits of Endocannabinoid Activation with Cannabidiol
Analgesic
The inflammatory reaction inside the joint causes a release of noxious stimuli and inflammatory mediators, leading to pain and loss of mobility. Activation of the endocannabinoid system has been shown to reduce pain signals in both the peripheral and central nervous system. The specific mechanism of action is thought to be through the excitation of the descending antinociceptive pathway as well as inhibition of painful inflammatory mediators.
Promotes Homeostasis
An unbalanced ratio of osteoclasts to osteoblasts or over expression of osteoclasts is characteristic of RA. Up-regulation of the endocannabinoid system has been shown, in animal models, to regulate bone growth and balance osteoblast differentiation and osteoclast formation.
The ECS has been implicated in maintaining homeostasis in a number of ways, specifically:
- Cannabinoids influence osteoclast-osteoblast binding.
- Osteoblast cultures from CB1 knockout mice express less RANKL (cytokines for osteoclast formation) reducing the potential for bone resorption.
- CB2 knockout mice show accelerated age-related osteoporosis.
- Activation of CB2 receptors increases bone formation markers
Possible Effect of Cannabidiol on Cells Associated with RA Inflammation
Fibroblast-like-synoviocytes (FLS)
CB2 receptors are highly expressed in FLS cells in patients with RA. Similarly CB2 activation leads to a reduction in inflammatory mediators (interleukin 1 and 6) as well as matrix metalloproteinases. Consequently, targeting CB2 receptors with CBD acts in a negative feedback manner to reduce inflammation in the synovial cavity.
Chrondrocytes
Chrondrocytes are proteins found on cell surfaces that are responsible for the binding of antibodies within the synovial cavity. The endocannabinoid system is postulated to downregulate chondrocyte proliferation.
T Cells
T cells are central to the inflammatory cascade and known to produce many signaling mediators. RA is characterised by an overexpression of T cells. The endocannabinoid anandamide inhibits proliferation of cytokines. CB2 agonists mediate anandamide reuptake. Generally the ECS, and especially CB2, has been shown to mediate the role of T cell-induced inflammation.
B Cells
B cells, especially “memory” white blood cells, produce antibodies and are the source of the rheumatoid factor (an antibody characteristic of RA). B cells exacerbate inflammation by unnecessarily activating T cells. Additionally B cells both respond to and produce chemokines and cytokines which produce inflammation. CB2 receptors on B cells have been shown to downregulate B cell proliferation.
Macrophages
Macrophages are non-specific white blood “killer” cells. The number of macrophages in the synovial cavity correlates well with joint erosion. CB2 agonism has been shown to suppress macrophage precursors and thus reduce inflammation.
Current Treatment
Traditional treatment of RA is geared towards the reduction of symptoms such as pain and inflammation using Non-Steroidal Anti-inflammatory Drugs (NSIADs). The newest class of medications used to treat RA is the disease-modifying anti-rheumatic drugs (DMARDs). These drugs work to normalise immune response by targeting specific immune modulators.
NSAIDs have exhibited side effects such as:
- Stomach problems including nausea ulcers and bleeding
- High blood pressure
- Fluid retention (causing swelling around the lower legs, feet, ankles and hands)
- Kidney problems
- Heart problems
- Rashes
The list of adverse effects for DMARDs differs markedly depending on the exact medication. Clinical studies suggest that CBD produces little to no adverse effects in the short or long term.
Pertinent Studies:
Azim, S., Nicholson, J., Rebecchi, M. J., Galbavy, W., Feng, T., Reinsel, R., … & Kaczocha, M. (2015). Endocannabinoids and acute pain after total knee arthroplasty. Pain, 156(2), 341-347.
Mechoulam, R., Parker, L. A., & Gallily, R. (2002). Cannabidiol: an overview of some pharmacological aspects. The Journal of Clinical Pharmacology, 42(S1), 11S-19S.
Richardson, D., Pearson, R. G., Kurian, N., Latif, L., Garle, M. J., Barrett, D. A., … & Chapman, V. (2008). Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritis. Arthritis Research and Therapy, 10(2), R43.
Gui, H., Tong, Q., Qu, W., Mao, C. M., & Dai, S. M. (2015). The endocannabinoid system and its therapeutic implications in rheumatoid arthritis.International immunopharmacology, 26(1), 86-91