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 — the CB1 receptor and the CB2 receptor.”  

 

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

 

What Are CB2 Receptors?

Cannabinoid receptors are an essential component of the body’s endocannabinoid system (ECS). Every function in our bodies requires balance, or homeostasis, to perform at maximum capacity. The ECS, which is made up of a network of endocannabinoid receptors, 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 cannabinoid receptor type 1 (CB1) and cannabinoid receptor type 2 (CB2). While they play slightly different roles in different parts of the body, both receptors are critical to the overall function of the cannabinoid system in the body. 

Where Are the CB1 and CB2 Receptors Located?

CB1 receptors are primarily active in your brain, central nervous system, lungs, liver, and kidneys. They are most prominent in the central nervous system, where they interact with neurons.

 

CB2 receptors, on the other hand, 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 in some bone and liver cells. Unlike CB1, the CB2 receptor isn’t typically found on neurons, except for in the brainstem and hippocampus. However, non-neuronal brain cells called microglia appear to express CB2 receptors in response to inflammation and injury.

Are There CB2 Receptors in the Brain?

CB1 receptors are much more common in the brain than CB2 receptors, which are expressed mostly in immune cells that travel throughout the body. However, a 2015 study found that “CB2 receptors and their genes are located in neurons that contain dopamine in the ventral tegmental area, a brain area that is involved in reward and drug addiction.” This study revealed that CB2 receptors may play a bigger function in brain-related activities than previously known.

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).

What Does the CB2 Receptor Do?

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.  

Does CBD Bind to CB2 Receptor?

There are no CBD-specific cannabinoid receptors in your body. Rather, cannabinoids like CBD and THC bind to CB1 and CB2 receptors, where they act as either agonists—mimicking endocannabinoids produced by your body and “activating” the receptors—or as antagonists—blocking cannabinoid receptors and limiting their activity.

 

According to an article published in the British Journal of Pharmacology, THC is a CB1 and CB2 agonist. That means that THC binds to cannabinoid receptors in your body and mimics the function and role of endocannabinoids (cannabinoids produced by your body). On the other hand, the study also found that CBD generally acts as a CB1 and CB2 antagonist, blocking cannabinoid receptors rather than activating them. This is why CBD is thought to counteract some of the effects produced by THC.