Can CBD Block The Effects of The Cancer-Causing Endocannabinoid Receptor GPR55?

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The more I research the Endocannabinoid System (ECS), the more I realize how wondrous and complicated it is. Have you ever heard of GPR55, the cancer-causing endocannabinoid receptor? I hadn’t either until just recently. Scientists have discovered that there is another endocannabinoid receptor, GPR55, which is very different from all the other known ECS receptors. Instead of supporting homeostasis, GPR55 increases the spread of cancer cells and tumor growth. But, don’t despair because researchers are hoping to prove their theory that the cannabinoid, CBD can block the effects of GPR55.

The ECS and its function was discovered in the 1990s while researchers were trying to understand the effects of THC on the human body. They discovered CB1 and CB2 endocannabinoid receptors and ananadamide and 2-AG, the cannabis-like chemicals that bind to them. They realized that ECS releases endocannabinoids in response to too little or too much activity which interferes with maintaining homeostasis.

G protein-coupled receptor 55, known as GPR55, is a receptor encoded by the GPR55 gene. It is found in tissue particularly in bones, heart, lungs, gastrointestinal tract, liver, kidney, bladder, uterus and nerve tissues. When first discovered, the binding molecule, known as the endogenous ligand, had not been identified. It is now known that the GPR55 receptor is activated by lysophosphatidylinositol (LPI) as well as anandamide and THC. Scientists have recognized the increase of GPR55 receptor activity in ovarian, breast, prostate, brain, skin, cervix, liver, blood, pancreas and bile ducts cancers. It also causes the reproduction of cancer cells.

Famed Spanish biologist, Dr. Cristina Sanchez, has been researching the effects of cannabis on cancer cells for several years, particularly in breast cancer patients. Her team discovered that “elevated GPR55 expression in human tumors is associated with the aggressive basal/triple-negative breast cancer population, higher probability to develop metastases, and therefore poor patient prognosis.” This information is particularly significant because it not only identifies GPR55 as a biomarker for this type of breast cancer, but it could help in the development of specific drugs to block its effects.

In a paper published last year in the International Journal of Cancer, Volume 142, Issue 1, a study was done using mice that were bred without the GPR55 receptor when compared to those with the GPR55 receptor. The results showed that the tumor burden (number of cancer cells, size of tumors or amount of cancer in the body) of mice with the GPR55 receptor was 50% more than those without it. They believe that the GPR55 receptor alters the levels of white blood cells which promotes tumor growth.

A 2011 paper published in Molecular Endocrinology set out to investigate the hypothesis that finding a GPR55 antagonist may prove beneficial in slowing tumor growth, reducing blood vessel formation that feeds the tumors and cancer pain. An antagonist would block signalling rather than binding with GPR55. The antagonist researchers had in mind was CBD.

Copious research studies on CBD have proven that it has many anticancer properties such as the inhibition of the growth of different kinds of breast cancer cells, reducing metastasis and facilitating cancer cell death. No study had established that this was a result of CBD’s ability to block the antitumoral effect of GPR55.

The proven anticonvulsive effects of CBD may shed some light on whether or not CBD may block the cancer-producing conditions associated with GPR55. A 2016 GW Pharma funded paper set out to investigate if the blocking of GPR55 by CBD could explain its anticonvulsant properties. Researchers realized that higher levels of LPI corresponded with excitatory synaptic transmission which is common during seizures. When CBD was introduced, the result was a reduction of this excitatory activity. This, more than likely, explained the well documented antiseizure effects of CBD. While this does not prove that CBD blocks GPR55 expression, it does prove that CBD does elicit biological changes in the body.

This is where the story about GPR55 gets really interesting. When I first read about GPR55, my initial thought was why would a cancer promoting endocannabinoid receptor exist? It seems that GPR55 has neuroprotectant properties as well. A study on mice was conducted at the same university where Dr. Sanchez did her research. Javier Ruiz, Professor of Biochemistry and Molecullar Biology at Complutense University of Madrid and his team found that those mice without the GPR55 receptor developed motor impairment. Even more exciting was the discovery that activating the GPR55 receptor “preserved neuronal integrity” which means that it is neuroprotective. There was also evidence of GPR55 changes in the central nervous system of those with neurodegenerative diseases.

This has left researchers even more perplexed about how the GPR55 receptor works. It seems that both GPR55 and CBD have neuroprotective properties and yet, CBD is thought to block the effects of GPR55. Clearly, there is much, much more to learn about how GPR55 functions. As researchers unlock the key to the mystery of the GPR55 receptor, the hope is that CBD will be proven to block its antitumoral effects. Stay tuned!

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