Cannabinoid Report: CB1/CB2 Receptors

November 20, 2019

Cannabinoid Receptor Type 1 and Cannabinoid Receptor Type 2 (more familiarly known as the CB1 and CB2 receptors) are two of the body’s major cannabinoid receptors, which are integral to the endogenous cannabinoid system as a whole. The CB1 receptor was discovered in the 1980s through in-vitro studies and was later cloned in 1990. The CB2 receptor was discovered and cloned in 1993 by researchers from Cambridge. Though many animals have an endocannabinoid system, only Chordata (mammals, birds, reptiles, amphibians, fish, etc.) have CB1 and CB2 receptors. The receptors are activated by agonists and inhibited by antagonists, both of which may be endogenous cannabinoids, phytocannabinoids, and synthetic cannabinoids. When cannabinoids bind with the receptors, they start to signal and send messages throughout the body for certain reactions to occur (such as the psychoactive effects of THC or the calming effects of CBD, for example.) The CB1 receptor is expressed primarily in the brain and central/peripheral nervous system, whereas the CB2 receptor is expressed primarily in the immune system. Studies show that the CB1 receptor plays a critical role in homeostasis of the central nervous system, whereas the CB2 receptor plays a critical role during neuroinflammation.


CB1 Receptor

The CB1 receptor is encoded in the CNR1 gene and is made up of 473 amino acids. It also has the same structure as all other G-protein-coupled receptors. Because the CB1 receptor is expressed at concentrated levels in the central nervous system, it is very involved in the effects of cannabinoids binding to the brain. CB1 receptor expression can be found in the following parts of the brain: hippocampus, olfactory bulb, thalamic nuclei, hypothalamic nuclei, cerebellar cortex, brainstem nuclei, basal ganglia, various cortical regions, and subcortical regions. Overall, CB1 receptors target pain perception, memory, motor activity and coordination, and appetite.

CB1 receptor expression can be found in many other parts of the body as well, such as the pituitary gland, thyroid gland, as well as in a variety of cells that have to do with metabolism (fat cells, liver cells, etc.) CB1 receptor expression can also be found in the lungs, kidney, retina, and digestive tract. The expression of the CB1 receptor may also play a part in the reproductive system, as it is present in testosterone-producing Leydig cells, sperm cells, ovaries, and may play a part in proper embryo development.

Activation of CB1 receptors in the hippocampus and basal ganglia can result in decreased excitement as well as reduced inhibition; because of this, movement and locomotor activity are affected in these regions (according to rat studies.) More human studies need to be conducted.

Activation of CB1 receptors may be useful in reducing pain, reducing inflammation, regulating anxiety, inhibiting gastrointestinal activity, maintaining homeostasis, and more. However, some recent studies show that activation of CB1 receptors can also reinforce drug-seeking behavior in drug addicts; therefore, CB1 antagonists can help to reduce this behavior.


CB2 Receptor

The CB2 receptor is encoded in the CNR2 gene and comprises about 360 amino acids. CB2 receptors are most often expressed in the immune system but are expressed in some neurons as well. Typically, CB2 receptors target CB2 receptor expression is found throughout the gastrointestinal system, thereby playing a large part in regulating intestinal inflammation (activation of the CB2 receptor may be therapeutically useful for Crohn’s disease, IBS, ulcerative colitis, and other inflammatory bowel diseases.) CB2 is also present in the spleen, tonsils, thymus gland, and peripheral blood mononuclear cells.

CB2 receptor expression may also be an effective agent in pain reduction, and, notably, may be useful for certain neurogenerative disorders like Alzheimer’s disease. Because of its anti-inflammatory properties, CB2 receptor activation may be useful in treating conditions such as multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and HIV Encephalitis.