If inflammation is the root of disease, cannabis is the cure.
by Christine Kielhorn, PhD
CB2 and the Immune System
The second cannabinoid receptor, CB2, does not produce any psychoactive effects but rather is thought to play an important role in regulating the immune system. In most cases, activating the CB2 receptor suppresses the immune response. This has many exciting therapeutic implications, which are discussed below.
CB2 Reduces Inflammation and the Immune Response
The CB2 receptor is found primarily in the cells of the immune system, like macrophages and lymphocytes. It is found in the brain, just not in the same high concentrations as the CB1 receptor. Within the brain, it is primarily found in glial cells, which are related to macrophages. Its high expression in these types of cells is indicative of a role in regulating immune responses.
The majority of studies surrounding the role of the CB2 receptor in immune regulation have been performed in vitro (on cells in culture) or in vivo (in animals, usually mice). Endocannabinoid interactions with the CB2 receptor generally result in inhibition of the immune response. Mice that have been genetically modified to lack the CB2 receptor (CB2 knockout mice) have been used in a number of studies to learn more about the role of CB2 receptors in disease. In general, these mice have intensified inflammatory responses compared to normal mice. In particular, these mice often experience an increase in the production of cytokines, pro-inflammatory molecules that amplify the immune response. In these mice, this often results in aggravating tissue damage. These studies demonstrated the importance of the CB2 receptor-activated pathways in the suppression of the immune inflammatory response.
Therapeutic Potential Using CB2 Receptors
Inflammation can cause tissue damage in many types of diseases or injury, and so these patients could benefit from a suppression of their immune response. So far, the affect of CB2 activation on disease has mostly been studied in animal models, with very few human clinical studies. However, genetic analysis of human patients has identified mutations in the DNA encoding for components of the endocannabinoid system. These patients also have changes in the expression of endocannabinoids or the CB2 receptor and are in inflammatory disease states. While more clinical studies will be necessary to support the following preclinical findings, the results and knowledge of the immune system are highlighting the CB2 receptor as a valuable medicinal target.
Activation of the CB2 receptor has been shown, in numerous studies, to improve outcomes in animal models for stroke or traumatic brain injury. When molecules that activate the CB2 receptor (agonists) are administered before simulating stroke in animals, or shortly afterward, the infarct volume, or volume of dead and dying tissue is reduced. In addition, activating CB2 receptors seemed to reduced immune cell invasion and other hallmarks of an immune response, which can frequently make the injury worse.
Autoimmune and inflammatory disorders, like rheumatoid arthritis (RA), could be excellent candidates for treatment via targeting of the CB2 receptor. Many studies on animal models of RA have found that CB2 agonists can reduce joint swelling and inflammation as well as decrease the number of leukocytes migrating into the joint. In addition, these studies have found that activating the CB2 receptor reduced joint damage. Inflammatory bowel disease could also potentially be improved by CB2 agonists. Mouse models of the disease had reduced inflammation and damage to the colon when treated with CB2 agonists.
Atherosclerosis is another disease that is caused and promoted by an inflammatory response. Plaque growth in the arteries is promoted by cytokines and other pro-inflammatory signals that recruit immune cells to the site. Immune cells, like foam cells (macrophages that contain a large amount of fat and cholesterols), are one of the main components of arterial plaques. CB2 agonists were able to reduce the formation of foam cells and the inflammatory response, therefore also reducing the size of plaques in animal models of atherosclerosis.
These are just a few of the examples from the preclinical research where CB2 agonists, such as those found in medical cannabis, were used to successfully reduce the inflammatory response in disease. As the research moves to the next stages, human clinical trials, we can hopefully begin to see new therapies develop.