Cannabinoids Activate CB2 Receptors, Resulting in a Damp Down of Arthritic Inflammation:
Medical cannabis eases the pain of rheumatoid arthritis (RA) and osteoarthritis (OA). Cannabinoids, like THC and CBD, are anti-inflammatory agents that reduce 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 the arthritic inflammation of RA and OA.
RA and OA have common joint destruction and inflammation in the lining of the joint. However, RA involves an autoimmune response that contributes to the worsening of joint destruction.
Increased Cannabioid Receptors Found in Inflamed Joints:
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 cytokines trigger an autoimmune response. Immune cells, in particular T-cells, then enter into the joint. These immune cells produce even more pro-inflammatory cytokines, resulting in an increasing 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.
CB2 receptors and 2-AG are found in the joint tissues of patients with arthritic inflammation, 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. Receptors in the endocannabinoid system strengthen anti-inflammatory effects.
Improve the Anti-Inflammatory Response:
Research indicates CB2 receptor activation triggers an anti-inflammatory response. 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. These compounds mute the immune response.
Reduce the Response of Immune Cells:
CB2 receptors also play a role in the immune response of RA 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 CB2pathway suppresses stimulation and migration of macrophages, another type of immune cell. These play a destructive role in RA.
Prevent Nerve Damage:
Studies revealed that 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.