A fairly recent discovery — the CB3 receptor — could go a long way towards unlocking the unexplained mysteries of cannabis.
Originally called GPR55 after the gene that encodes it, the CB3 receptor has been up-ending expectations since researchers found it. Every new finding provides more explanations about the mechanisms by which cannabis works within the body.
The CB3 stayed stayed hidden from scientists because it’s so unlike the other cannabinoid receptors. It only shares fourteen percent of amino acid identity with them. It simply doesn’t look like it would react with cannabis, so scientists on the hunt for new receptors passed over it for years.
Even after it was discovered in 1999, many doubted it was a cannabis receptor. It wasn’t until real proof came along years later (finally confirmed through a 2008 study published in the journal PNAS) that medical researchers accepted that GPR55 was actually CB3.Lauckner, Jane E. et al. (2008). GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. PNAS. 105(7) 2699-2704. https://www.pnas.org/content/105/7/2699.
Now, more recent research on the CB3 receptor is ushering in an era of new possibilities that may finally explain the unsolved mysteries of cannabis medicine.
A Closer Look at the CB3 Receptor
The CB3 receptor is a G-protein coupler receptor that is scattered throughout the body, but concentrated in the brain and guts. It is most densely packed in the brain’s cerebellum region, which controls the body’s motor functions, such as walking and speech.
Once it was discovered, scientists had to figure out what the GPR55 receptor did. Early research sponsored by companies like Astra Zeneca and Glaxo Smith Kline focused on GPR55 as a possible mechanism by which to control blood pressure.
Slowly but surely, researchers began to see 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.Ryberg, E. et al. (2007). The orphan receptor GPR55 is a novel cannabinoid receptor. British Journal of Pharmacology. 152(7) 1092-1101. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/.
But it wasn’t until the 2008 PNAS study that scientists learned what actually happens when a cannabinoid interacts with GPR55. When THC enters the body and meets a CB3 receptor, it increases intracellular calcium and inhibits the M current in the brain. While the full ramifications of these findings are not clear, they are the first steps toward understanding how the CB3 receptors influence changes in the body and mind.Lauckner, Jane E. et al. (2008). GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. PNAS. 105(7) 2699-2704. https://www.pnas.org/content/105/7/2699.
Building off that research, a 2017 study published in cancer journal Oncotarget showed, beyond all doubt, that GPR55 expression correlates strongly with the cancer cells that are about to metastasize. In other words, it’s kind of like the canary in the coal mine of cancer spreading.Mangini M. et al. (2017). Peptide-guided targeting of GPR55 for anti-cancer therapy. Oncotarget. 8(3) 5179-5195. https://www.ncbi.nlm.nih.gov/pubmed/28029647.
Scientists reasoned that if CB3 receptors could be manipulated — most probably by cannabinoids — they might be able to stop the spread of cancer by killing their signaling device. Or, to put it another way, the scientists may now know where to look in deciphering the potential anti-cancer effects of cannabis.
While some scientists were busy trying to unlock the mysteries of cannabis and cancer by exploring the CB3 receptor, others saw its potential to explain yet another puzzle: the relationship between cannabis and epilepsy.
It’s long been shown that cannabis can have anti-seizure properties. The first cannabis-based drug approved by the American FDA is currently in use to treat epilepsy. Scores of seizure sufferers have found their lives transformed by just a few drops of cannabis or by smoking a single joint.
But despite the preponderance of evidence, there’s still not a satisfying explanation for why cannabis has such powerful anti-seizure properties. The CB3 receptor in the part of the brain responsible for motor functioning seemed like a smart bet.
In 2017, a group of scientists publishing in the journal PNAS, broke the concept wide open. It was already confirmed that CBD reduced the frequency of, and severity of, seizures in patients with Dravet Syndrome, a rare childhood form of epilepsy. But the new study went a step further in explaining just how it worked.Kaplan, Jonathan H. (2017). Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome. PNAS. 114 (42) 11229-11234. https://www.pnas.org/content/114/42/11229.
The scientists discovered that all those symptoms of Dravet Syndrome — as well as the autistic-like social deficits that often accompany the disease — are mediated by CBD in part through the CB3 receptor.
A Dravet Syndrome patient, Charlotte Figi, galvanized American support of medicinal cannabis. It came through CNN’s 2003 documentary “Weed.”
The film shows how when patients take CBD, the brain undergoes a crucial change. This change, which prevents the seizures and asocial effects the disorder creates, has long been mysterious. But the research shows that CBD activates the CB3 receptor, which in turn inhibited neurotransmissions responsible for Dravet Syndrome effects.
The Next Steps
The excitement over a confirmed new kind of cannabinoid receptor in the brain and guts is not just good news for cannabis-based medicine. It’s good news for all kinds of medicine.
As scientists better understand the full scope and function of the human endocannabinoid system, they are closer to understanding a vital and multifaceted component of the central nervous system. The more medicine understands this system, the better it will be able to treat all diseases and disorder — whether it’s through cannabis-based treatments or not.
Other Ways to Activate CB3?
More than just cannabinoids activate the CB3 receptor. There are also other lipids and peptides that work with and through it to produce changes in the body’s neurochemistry. Advances in these areas could prove just as important as new cannabinoid-based discoveries.
The bulk of new information is likely to explain the behavioral, vascular, and immunological functions of cannabis in the body. What new treatments this will lead to is anyone’s guess, but a new avenue for explanation offers a lot to be excited about.
|↑1, ↑3||Lauckner, Jane E. et al. (2008). GPR55 is a cannabinoid receptor that increases intracellular calcium and inhibits M current. PNAS. 105(7) 2699-2704. https://www.pnas.org/content/105/7/2699.|
|↑2||Ryberg, E. et al. (2007). The orphan receptor GPR55 is a novel cannabinoid receptor. British Journal of Pharmacology. 152(7) 1092-1101. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2095107/.|
|↑4||Mangini M. et al. (2017). Peptide-guided targeting of GPR55 for anti-cancer therapy. Oncotarget. 8(3) 5179-5195. https://www.ncbi.nlm.nih.gov/pubmed/28029647.|
|↑5||Kaplan, Jonathan H. (2017). Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome. PNAS. 114 (42) 11229-11234. https://www.pnas.org/content/114/42/11229.|