"GPR55 The third Cannabinoid Receptor (CB3)"

Finding the CB3 receptor could mean huge medical advancements for cannabis medicine.Originally called GPR55 after the gene that encodes it, the CB3 receptor is an exciting discovery for science. It is now clear this receptor is part of the Endocannabinoid System and interacts with endocannabinoids and phtyocannabinoids like THC and CBD.

Every animal, have an Endocannabinoid System. Cannabinoid receptors are found throughout the body. But where has CB3 been hiding? Well, turns out it hasn’t exactly been hiding. It’s more like researchers didn’t connect it to endocannbinoid activity before now.

Firstly, the two most researched receptors are CB1 and CB2. While CB1 receptors are prominent in the central nervous system, and CB2 receptors typically reside in the immune system. CB3 receptors were incognito, previously identified as GPR55. At first, science didn’t know that this receptor even accepted cannabinoids.

The CB3 receptor stayed hidden from scientists because it’s so unlike the other cannabinoid receptors. It only shares 13% of amino acid identity with them. It simply doesn’t look like it would react with cannabis, so scientists on the hunt for new cannabinoid receptors passed over it for years. This designation means that while the receptor had been found, science doesn’t yet know what activated that receptor.

When CB3 was first discovered in 1999, many doubted it was a cannabis receptor. It wasn’t until real proof came along years later that medical researchers accepted that GPR55 was indeed the 3rd Cannabinoid Receptor.

Endocannabinoid system: Essential and mysterious

Many of us have heard of some of the transmitter systems within our bodies, such as the nervous system, which gives us our fight-or-flight response. Fewer have heard of the more recently discovered endocannabinoid system which is amazing when you consider that the ECS is critical for almost every aspect of our moment-to-moment functioning. 

The ECS regulates and controls many of our most critical bodily functions such as learning and memory, emotional processing, sleep, temperature control, pain control, inflammatory and immune responses, and eating. The ECS is currently at the center of renewed international research and drug development.

What is the ECS?

The ECS comprises a vast network of chemical signals and cellular receptors that are densely packed throughout our brains and bodies. The "cannabinoid" receptors in the brain — the CB1 receptors — outnumber many of the other receptor types on the brain. They act like traffic cops to control the levels and activity of most of the other neurotransmitters. This is how they regulate things: by immediate feedback, turning up or down the activity of whichever system needs to be adjusted, whether that is hunger, temperature, or alertness.

A second type of cannabinoid receptor, the CB2 receptor, exists mostly in our immune tissues and is critical to helping control our immune functioning, and it plays a role in modulating intestinal inflammation, contraction, and pain in inflammatory bowel conditions. CB2 receptors are particularly exciting targets of drug development because they don’t cause the high associated with cannabis that stimulating the CB1 receptors does (which is often an unwanted side effect).

To stimulate these receptors, our bodies produce molecules called endocannabinoids (also called endogenous cannabinoids), which have a structural similarity to molecules in the cannabis plant, the anandamide (AEA) & the 2-arachidonoylglyerol (2-AG)

Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

The discovery that botanical cannabinoids such as THC exert some of their effect through binding specific cannabinoid receptor sites,has led to the discovery of the Endocannabinoid Signaling System, which in turn has spurred research into the mechanisms of action and addiction potential of cannabis.

This paper reviews current understanding of CB1, CB2, and other possible cannabinoid receptors, their arachidonic acid derived ligands (e.g. anandamide 2 arachidonoyl glycerol), and their possible physiological roles. CB1 is heavily represented in the central nervous system, but is found in other tissues as well CB2 tends to be localized to immune cells. Activation of the endocannabinoid system can result in enhanced or dampened activity in various neural circuits depending on their own state of activation.

This suggests that one function of the endocannabinoid system may be to maintain steady state. The therapeutic action of botanical cannabis or of synthetic molecules that are agonists, antagonists, or which may otherwise modify endocannabinoid metabolism and activity indicates they may have promise as neuroprotectants, and may be of value in the treatment of certain types of pain, epilepsy, spasticity, eating disorders, inflammation, and possibly blood pressure control.