Arthritis is a group of multiple diseases characterized 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 for arthritis although many common medications provide symptomatic relief, as opposed to treating the cause of disease itself. Roughly 95% of cases of arthritis are classed as either osteoarthritis or rheumatoid arthritis.
Osteoarthritis is a characterised by progressive cartilage degradation, leading to inflammation, pain, abnormal bone growth and loss of mobility. Osteoarthritis is commonly associated with a reduction in joint cartilage, and compromised bone integrity.
In addition to reducing the painful inflammatory symptoms of osteoarthritis, the endocannabinoid system has also been implicated in the bone remodelling process and has been suggested to prevent abnormal bone growth.
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
Bone remodelling is the essential process by which bone is mineralized and repaired. Various hormones, peptides and cytokines coordinate this constantly occurring process. The key cells involved in bone remodelling are osteoclasts, osteoblasts and osteocytes. These cells all also express CB2 receptors suggesting the endocannabinoid system plays an important modulatory role.
The endocannabinoid system 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.
Activation of the the endocannabinoid system has been shown to modulate the inflammation by acting at a number of key junctions within the inflammatory cascade. endocannabinoid system is postulated to modulate:
- Macrophage and mast cell activation
- Proinflammatory cytokines
- T cell proliferation and apoptosis
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 endocanabbinoid 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.
Traditional treatment of osteoarthritis is heavily geared towards the reduction of symptoms such as pain and inflammation. Non-Steroidal Anti-inflammatory Drugs (NSIADs) are most commonly used.
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
The endocannabinoid system shows great promise in relieving both the underlying cause of osteoarthritis as well as providing symptomatic relief from pain and inflammation without any documented adverse effects in the short or long term
Buckley, N. E., McCoy, K. L., Mezey, É., Bonner, T., Zimmer, A., Felder, C. C., … & Zimmer, A. (2000). Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB 2 receptor. European journal of pharmacology, 396(2), 141-149.
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.
Malfait, A. M., Gallily, R., Sumariwalla, P. F., Malik, A. S., Andreakos, E., Mechoulam, R., & Feldmann, M. (2000). The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proceedings of the National Academy of Sciences, 97(17), 9561-9566.
Huggins, J. P., Smart, T. S., Langman, S., Taylor, L., & Young, T. (2012). An efficient randomised, placebo-controlled clinical trial with the irreversible fatty acid amide hydrolase-1 inhibitor PF-04457845, which modulates endocannabinoids but fails to induce effective analgesia in patients with pain due to osteoarthritis of the knee. PAIN®, 153(9), 1837-1846.
Idris, A. I., Sophocleous, A., Landao-Bassonga, E., Canals, M., Milligan, G., Baker, D., … & Ralston, S. H. (2009). Cannabinoid receptor type 1 protects against age-related osteoporosis by regulating osteoblast and adipocyte differentiation in marrow stromal cells. Cell Metabolism, 10(2), 139-147.