CB2 (Cannabinoid-2 Receptor)

Kə-ˈna-bə-ˌnȯid ˈtü ‘ri-ˈsep-tər | Noun

An important protein in the body’s endogenous cannabinoid system that is heavily involved in the body’s immune system, and plays an important role in fighting inflammation.


“The body has two main cannabinoid receptors — CB1 and CB2.”  


“Your CB2 Receptors are most commonly found on immune cells.”


More About CB2

Cannabinoid receptors are an essential component of the body’s endogenous, or endocannabinoid system (ECS). Every function in our bodies requires balance, or homeostasis, to perform at maximum capacity. The ECS helps the body maintain homeostasis through its three main components: “messenger” molecules called cannabinoids, the receptors that these molecules bind to, and the enzymes that break them down for the body to synthesize. Pain, stress, appetite, energy metabolism, cardiovascular function, reward and motivation, reproduction, and sleep are all functions that the ECS can modulate.


The body’s most studied cannabinoid receptors are the Cannabinoid-1 and Cannabinoid-2 receptors (CB1 and CB2). CB2 receptors are mostly found on immune cells, which circulate throughout the body and brain via the bloodstream. They’re also found in the spleen, as well as some bone and liver cells.


Unlike CB1, which is most prominent throughout the central nervous system, CB2 isn’t typically found on neurons, except for on the brainstem and hippocampus. However, non-neuronal brain cells called microglia appear to express CB2 receptors in response to inflammation and injury.

CB2 Structure

Both CB2 and CB1 are g-protein coupled receptors (GPCR), a large and diverse group of cell membrane receptors, that connect with and activate intracellular messenger proteins of the Gi/Go family. Scientists have not yet elucidated the exact 3D structure of the CB2 protein as they have for CB1, so our understanding of how molecules bind to the CB2 is somewhat limited in comparison to CB1.


CB2 receptors span the cell membrane or “wall” with its active binding side facing outward. Similar to a deadbolt, CB2 receptors act like a lock waiting for its key. Both endogenous and phytocannabinoids (cannabinoids from outside the body) find active CB2 receptors and “unlock” them. G-proteins, located on the inside of the cell, bind to the tail of a CB2 receptor, then release to deliver messages when the CB2 receptor is activated by a cannabinoid or other agonist (an “activating” molecule).


In humans, the CB2 protein is encoded, or produced by the CNR2 gene. Like all other proteins our bodies make, the “blueprints” for how to build them reside in our DNA. Random or inherited edits or mutations in these blueprints are extremely common. Scientists have discovered several different versions, or mutations in the CNR2 gene (the CB2 receptor blueprint) in humans. This may, at least partially, account for some of the differences in human reactions to cannabis compounds such as CBD and tetrahydrocannabinol (THC).

Function of CB2

CB2 is a strong target of 2-arachidonoylglycerol (2-AG), and more weakly, anandamide — the two most prominent and well-researched endogenous cannabinoids (endocannabinoids), or cannabinoids produced inside the body. After being released from a CB2 receptor, g-proteins activate a number of other proteins and intracellular processes, including those associated with immune regulation. Activity at the CB2 is like a cellular switch, turning on intracellular processes that promote homeostasis — primarily regulating inflammation, as well as cell survival and proliferation.

CB2 Activation

CB2 receptors are only present in the brain when there is inflammation or injury. When inflammation occurs, CB2 activity inhibits inflammatory signaling pathways, bringing things back to a normal non-inflammatory state, or a state of homeostasis.


Cannabinoids can have anti-inflammatory effects when they engage the ECS by binding to CB2 receptors. When chronic opioids cause pro-inflammatory responses, CB2 activation can inhibit these responses as well, research published by the American Pain Society has found. Diminishing opioid tolerance is a valuable tool in protecting people from opioid overdose. CB2 activation could play a valuable part in treating opioid dependence and tolerance.  


CB2 activation may also play a role in minimizing stroke symptoms according to research published by the American Heart Association and American Stroke Association. Because inflammation accounts for a large portion of the neural damage caused by strokes, CB2 activation may have a neuroprotective effect on potential stroke victims.


A mutation of the CB2 gene may also be involved in some forms of osteoporosis and other autoimmune diseases. Though CB2 activation has generally been found to promote bone health by correcting imbalances in the immune system, a 2005 study found that patients with this CB2 gene mutation showed reduced immune responses that could put them at risk for an autoimmune disorder.