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research focus 9 cannapatientcare.com july/august 2022 | cannabis patient care a patient's own body, it causes damage to the affected areas. The direct damage then causes problems with interconnect- ed activities. For example, in the case of multiple sclerosis, the immune system attacks myelin sheaths on nerve fibers. This impedes signaling between the brain, spinal cord, and the rest of the body, leading to problems such as limb numbness, tremors, and pain. The second set of problems caused by autoimmune disease is collateral damage to nearby cells and tissues associated with the ongoing swelling and irritation of the immune system. There are no cures for autoimmune disease. There are, how- ever, treatments that focus on reducing immune system activ- ity (that is, immunosuppressants), such as painkillers, anti-in- flammatories, cortisone pills, and creams (5). Research on Cannabis and Autoimmune Disease Since autoimmune disease involves malfunction of the immune system, the same research on cannabis and immune system disorders applies to autoimmune disease. As with more tradi- tional treatments for autoimmune disease, cannabis tends to address immune system disorders by decreasing inflammation and swelling. Mechanisms of Action There are a host of in vitro and in vivo studies examining how cannabis works to treat the symptoms and causes of autoim- mune disease. Autoimmune Disease Generally Let's start with cannabis's mechanisms of actions (MoAs) for autoimmune disease generally. The primary way cannabinoids influence cells is by binding to receptors that are located on cell surfaces, thereby inducing activity. Cannabinoid type 2 receptors (CB2) are densely located on all different types of immune system cells. Generally speaking, then, cannabis helps treat autoimmune disorders by binding to cannabinoid receptors on immune system cells, causing decreases in im- mune system activity. Four immunosuppressive mechanisms of action in particular enable cannabis to relieve symptoms from autoimmune disorders. 1. Induce cell death: Apoptosis is a natural process used by the body to rid itself of unneeded or abnormal cells. Cannabinoids induce apoptosis in white blood cells in- volved in the inflammation process (that is, killer T cells), thus alleviating the inflammatory response (6-8). 2. Inhibit cell proliferation: Cell proliferation is the speed at which cells replicate themselves. Cannabinoids inhib- it cell proliferation in white blood cells involved in the inflammation process (that is, killer T cells, B cells), thus alleviating the inflammatory response (6-9). 3. Suppress cytokine production: Cytokines are part of the entourage of immune system cells; one of their func- tions is to help either amplify or limit inflammatory responses. Autoimmune disease may cause malfunc- tions in the immune system that cause long-term pro- duction of pro-inflammatory cytokines (7). Cannabinoids suppress cytokine production, thus alleviating the in- flammatory response (6,7,9,10). 4. Induce regulatory T cell production: Finally, cannabi- noids induce production of white blood cells that sup- press the cytokine production (that is, regulatory T cells), thus mitigating inflammatory responses associat- ed with autoimmune disease (7,8,11). Specific Autoimmune Diseases Aside from addressing general autoimmune dysfunction, studies have also established cannabis's MoAs for addressing specific autoimmune diseases. Crohn's disease and IBD: Studies have shown that the en- docannabinoid system regulates intestinal inflammation (6) and intestinal motility (movement of substances through the gastrointestinal tract) (12). Multiple sclerosis: Studies have shown that cannabis may inhibit the inflammatory response in MS that contributes to the destruction of myelin and myelin-producing cells. By in- hibiting these inflammatory responses, cannabis mitigates MS-induced bladder control problems, pain, spasticity, and tremors (13). Rheumatoid arthritis: Studies have shown that cannabis in- hibits progression and proliferation of RA generally by induc- ing cell death that reduces bone tissue degeneration (7). Stud- ies have also shown that cannabinoid receptors are located in the synovia, that is the fluid-filled cavities, which keep bones together and permit free bone movement. In the synovia, can- nabinoids prevent the progression of RA by reducing synovial inflammation and bone destruction (6). Clinical Studies Crohn's disease and IBD One large-scale retrospective study of patients with Crohn's Disease (14) and several other much smaller studies concluded that patients found substantial improvements in their symp- toms after using cannabis. MS MS is one of the most-studied diseases for cannabis treatment. Dozens of clinical studies, including a good number of mod- erately-sized randomized controlled trials, have found that cannabis may improve MS-related bladder control problems, pain, spasticity, and tremor. RA "There are currently no randomized clinical trials investigating the use of cannabis in the treatment of RA, partly because of the availability of effective biological anti-inflammatory agents in the therapeutic armamentarium. However, one preliminary