Unlock the medical potential of the CB3 receptor
Originally called GPR55, from the name of the gene that encodes it, the CB3 receptor has shaken expectations since researchers discovered it. Each new discovery provides more insight into the mechanisms by which cannabis works in the body. Cannabinoid receptors are present throughout the bodys, so where was the CB3 hiding?
The two most studied receptors are the CB1 and CB2. While CB1 receptors are predominant in the central nervous system, CB2 receptors are found in the immune system. CB3 receptors were hidden incognito under the name GPR55. At first, science did not know that this receptor accepted cannabinoids.
What is the CB3 receptor?
CB3 has remained hidden from scientists because it is very different from other cannabinoid receptors. It shares with them only fourteen percent amino acid identity. It just doesn't seem to be able to respond to cannabis, so scientists looking for new cannabinoid receptors have ignored it for years. The other name of CB3 is GPR55. It is also identified as an orphan receptor. This designation means that if the receptor has been discovered, science does not yet know what activates it.
CB3 was discovered in 1999, but many doubted it was a receptor for cannabis. It wasn't until real evidence emerged years later (finally confirmed by a 2008 study published in the journal PNAS) that medical researchers accepted that GPR55 was in fact CB3.
Today, more recent research on the CB3 receptor opens up an era of new possibilities that could finally explain the unsolved mysteries of cannabis medicine.
A closer look at the CB3 receiver
The CB3 receptor is a G protein coupler receptor that is dispersed throughout the body, but concentrated in the testes, spleen, and brain. CB3s are also found in the small intestine. It is most dense in the cerebellum region of the brain, which controls motor functions of the body, such as walking and speaking.
After its discovery, scientists had to figure out what the GPR55 receptor was doing. Early research sponsored by companies like Astra Zeneca and Glaxo Smith Kline focused on GPR55 as a possible blood pressure control mechanism.
Slowly but surely, researchers began to view GPR55 as a true cannabinoid receptor. A study published in the British Journal of Pharmacology (2007) found that several cannabinoids, including CBD, could potentially bind to GPR55.
Confirmation of the role of cannabinoid receptors - CB3
But that's only in the PNAS study of 2008 that scientists learned what actually happens when a cannabinoid interacts with GPR55. When THC enters the body and encounters a CB3 receptor, it increases intracellular calcium and inhibits M-current in the brain. Essentially, this means that it can control neuronal excitability and therefore have applications in maintaining healthy brain function.
Although all ramifications of these findings are unclear, they are the first steps in understanding how CB3 receptors influence changes in body and mind.
The CB3 receptor and cancer
Based on this research, a study of 2017 published in the cancer journal Oncotarget has shown, beyond a shadow of a doubt, that GPR55 expression is strongly correlated with cancer cells that are on the verge of metastasis. In other words, it's a bit of a canary in the coal mine of the spread of cancer.
Scientists thought that if CB3 receptors could be manipulated - most likely by cannabinoids - they might be able to stop the spread of cancer by killing their signaling device. Or, to put it another way, scientists may now know where to look to decipher the potential anti-cancer effects of cannabis.
Cannabinoid receptors and epilepsy
While some scientists attempted to unravel the mysteries of cannabis and cancer by exploring the CB3 receptor, others saw its potential to explain another conundrum: the relationship between cannabis and epilepsy.
Cannabis has long been shown to have anti-seizure properties. The first cannabis-based drug approved by the US FDA is currently used to treat epilepsy. Dozens of people with seizures have had their lives transformed by just a few drops of cannabis or by smoking a single joint.
But, despite the preponderance of evidence, there is still no satisfactory explanation as to why cannabis has such potent anti-seizure properties. Having the CB3 receptor concentrated in the part of the brain responsible for motor function seemed like a smart bet.
In 2017, a group of scientists, publishing in the journal PNAS, broke this concept. CBD was already confirmed to reduce the frequency and severity of seizures in patients with Dravet syndrome, a rare form of childhood epilepsy. But the new study went further by explaining how it worked.
The next steps in CB3 receptor research
The excitement over the confirmation of a new type of cannabinoid receptor is not only good news for cannabis-based medicine. This is good news for all types of medicine. As scientists gain a better understanding of the extent and function of the human endocannabinoid system, they come closer to understanding a vital and multifaceted component of the central nervous system. The more medicine understands this system, the better able it will be to treat multiple diseases and disorders - whether through cannabis treatments or not.
