Cannabis Reduces Inflammation Using CB2 Receptors

If inflammation is the root of disease, cannabis might be able to help with that.  

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 we will discuss below; but it mainly reduces Inflammation.

CB2 Reduces Inflammation and the Immune Response

The CB₂ receptor appears primarily in the cells of the immune system, like macrophages and lymphocytes. It also appears in the brain, just not in the same high concentrations as the CB₁ receptor. Within the brain, it is primarily 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 on the role of the CB₂ receptor in immune regulation take place in vitro (on cells in culture) or in vivo (in animals, usually mice). Endocannabinoid interactions with the CB₂ receptor generally inhibit the immune response. A number of studies use genetically modified mice, lacking the CB₂ receptor (CB₂ knockout mice) to learn more about the role of CB₂ receptors in disease. In general, these mice have intensified inflammatory responses compared to normal mice. These mice in particular 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. These patients can benefit from a suppressed immune response. So far, the affect of CB₂ activation on disease has been studied in animal models. There have been very few human clinical studies. However, genetic analysis of human patients identifies mutations in the DNA encoding for components of the endocannabinoid system. Also, these patients have altered expression of endocannabinoids or the CB₂ receptors. These receptors are in “inflammatory disease” states. Overall, more clinical studies will be necessary to support future preclinical findings. Still, however, the results and knowledge of the immune system are highlighting the CB₂ receptor as a valuable medicinal target.

Activation of the CB₂ receptor improves outcomes in animal models of strokes or traumatic brain injuries. When scientists activate the CB₂ receptor (agonists) before or just after administering a simulated stroke in animals, the volume of dead and dying tissue (infarct) sees reductions. In addition, activating CB₂ receptors reduces immune cell invasion and other hallmarks of an immune response. This frequently makes the injury worse.

Autoimmune and inflammatory disorders could be excellent candidates for treatments targeting the CB₂ receptor. This could even treat rheumatoid arthritis (RA). Many studies on animal models of RA have found that CB₂ agonists can reduce joint swelling and inflammation, and decrease the number of leukocytes migrating into the joint. In addition, these studies find that activated CB₂ receptors helps reduce joint damage. CB₂ agonists could also potentially improve inflammatory bowel disease symptoms. Mouse models of the disease show reductions in inflammation and colon damage when treated with CB₂ agonists.

Atherosclerosis and Other Diseases

Atherosclerosis is another disease that is caused and promoted by an inflammatory response. Cytokines promote plaque growth in the arteries and other pro-inflammatory signals recruiting immune cells to the site. Immune cells are one of the main components of arterial plaques.like foam cells (macrophages that contain a large amount of fat and cholesterols), 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.