Cannabinoids activate CB2 receptors, resulting in a muting of the inflammatory response of RA and OA.
Medical cannabis can be used to ease the pain resulting from rheumatoid arthritis (RA) and osteoarthritis (OA). Cannabinoids, like THC and cannabidiol (CBD), act as anti-inflammatory agents to reduce the swelling and pain in the joints of arthritis patients. Additionally, there have been increasing numbers of laboratory studies performed on cells (in vitro) and in animals (in vivo) that suggest cannabinoids may also have a therapeutic benefit for RA and OA.
First, RA and OA have common joint destruction and inflammation of the lining of the joint (synovium). However, RA is also characterized by an autoimmune response that contributes to the worsening of the inflammation and destruction of the joint.
In RA, inflammation of the joint tissue causes abnormal growth of cells called Fibroblastlike Synoviocytes (FLSs). These cells produce a large number of pro-inflammatory proteins, or cytokines, and matrix metalloproteases (MMPs). The cytokines frequently studied in the progression of RA are: interleukins (IL) (like IL-1, IL-6, and IL-8) and tumor necrosis factor (TNF-α).
The increased numbers of these pro-inflammatory signals trigger an autoimmune response, in which immune cells, in particular T-cells, enter into the joint. These immune cells produce even more pro-inflammatory cytokines, resulting in an amplifying of the inflammation. As a result, the joint begins to break down because the immune response increases the formation of osteoclasts. These are special cells that break down and absorb bone. The large number of MMPs produced contribute to joint destruction by breaking down cartilage.
Cannabinoid receptors, in particular the CB2 receptor, and the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG) have been found in the joint tissues of arthritis patients, but not in healthy subjects. The endocannabinoids, anandamide and 2-AG, are produced naturally in the body, and so this data suggests that the endocannabinoid system is likely part of an anti-inflammatory feedback loop. Targeting the receptors in the endocannabinoid system could help strengthen the anti-inflammatory effect and perhaps be used to treat RA and OA.
Here are a few examples of how cannabinoids have demonstrated effective treatment of arthritis:
Improve the Anti-Inflammatory Response of Our Endocannabinoid System
The research indicates that an anti-inflammatory response is triggered by the activation of the CB2 receptor. This is helpful for therapies because the CB2 receptor is not associated with the psychotropic effects of cannabis. Synthetic cannabinoids designed specifically to bind to the CB2 receptor were able to reduce the production of the pro-inflammatory cytokines and MMPs discussed above. With the production of these compounds turned down, the immune response was also muted.
Reduce the Response of Immune Cells
The CB2 signalling pathway also plays a role in the immune response of RA, in particular by influencing T-cells in a variety of ways. For example, cannabinoids binding to the CB2 receptor on T-cells reduced the production of pro-inflammatory cytokines, as they were able to do in FLSs. In addition, cannabinoids promoted a healthy balance of the good (regulatory T-cells, which help suppress inflammation) and the bad (T helper cells, which promote inflammation). The CB2 pathways have also been shown to suppress stimulation and migration of macrophages, another type of immune cell, which also play a destructive role in RA.
Prevent Nerve Damage
Studies on mice lacking CB2 receptors had increased osteoclast production. Additionally, activating signalling pathways via the CB2 receptor also reduced osteoclast formation. This is likely related to the anti-inflammatory effect, because osteoclasts are derived from macrophages, a type of immune cell. The cytokines and other signals produced in the inflammatory response help to turn macrophages into osteoclasts
Treatment of arthritis with cannabis could, therefore, help to calm the auto-immune response, reduce the inflammation of the joint, and slow the pace of bone loss and joint destruction in RA and OA.