The GPR55 Receptor and How CBD Interacts With It


GPR55 is a “G protein receptor” that is embedded within the cell membrane. This is where the “GPR” part of the name comes from. G protein receptors are a very broad family of cell membrane receptors that all have a similar sinuous structure, crossing through the cell membrane seven times. All G protein receptors receive signals from outside the cell which they can then transmit across the membrane and sparks a particular reaction inside the cell.

Okay… if your eyes are glazing over from boredom, please hang in there because we promise we’re going to get to stuff you’ll find really fascinating by the end of the article!

If you have researched the benefits of CBD oil, you’ve no doubt read something about CB1 and CB2 cannabinoid receptors in the endocannabinoid system. That’s because CB1 and CB2 were the first cannabinoid receptors to be discovered so there is a lot more known about them. Like GPR55, CB1 and CB2 receptors are also members of the G protein receptor family. They are also a subset of that family called cannabinoid receptors because they respond to the signals of molecules classified as cannabinoids. While CB1 and CB2 have been studied a long time, it’s only been in the last couple of decades that scientists have become increasingly aware that there are very likely several more G protein receptors that also fall into the subcategory of G protein receptors known as cannabinoid receptors and are thus part of the endocannabinoid system.

The GPR55 receptor was discovered in 1999, mapped out, and cloned so its gene sequence could be studied. When we say “discovered” we mean that 1999 is when scientists actually began to really understand specifically what it was and know how to distinguish it from all the other G protein receptors. Basically, it had hiding in plain sight for decades.

By comparing the GPR55 receptor’s gene sequences to other known receptors, including CB1 and CB2, and by studying its physical structure, scientists began to consider the possibility that the GPR55 receptor might be another cannabinoid receptor. This realization sparked huge interest and a flurry of research activity began to take place, much of it funded by Big Pharma, hoping to find exactly what biochemical reactions and physiological processes GPR55 induced. These researches were also intent on finding out exacting which cannabinoids were able to interact with the GPR55 receptor — and how each one reacted with it.

It’s important to understand at this juncture that cannabinoid receptors can be influenced by cannabinoids of three different origins:

1. Endogenous Cannabinoids: cannabinoids produced internally by the human body. These are often called endocannabinoids.

2. Plant Cannabinoids: these are cannabinoids that are found in the essential oil of various plants, with the most famous being cannabis. They include the famous CBD and THC found in cannabis but also many others. These plant cannabinoids are sometimes called phytocannabinoids.

3. Synthetic Cannabinoids: These are “artificial” cannabinoids created in a laboratory environment. They are usually modelled after an endogenous cannabinoid or a plant cannabinoid but they can never be exactly the same as a natural cannabinoid.

Now, we’ll get to the most interesting part of this.

After testing various types of endogenous, plant, and synthetic cannabinoids against the GPR55 receptor, it turns out that CBD reacts with it, and more importantly, CBD reacts strongly with it.

It also turns out that CBD is an antagonist to GPR55, meaning CBD can block GPR55 from expressing itself. This turns out to be very important because the activation of GPR55 is sometimes associated with various diseases like osteoporosis and several times of cancer!

Let’s look at osteoporosis first. This disease results in the demineralization of the bones, a corresponding decrease in the density of bones, and overall bone loss. Osteoclasts are a special type of bone cell that are involved in breaking down bones. They serve an important function in breaking down old bone so new bone can form. They are also important in mending a bone when it’s been fractured or broken. However, if these osteoclasts begin to be too aggressive, this can result in significant bone loss where new bone growth can’t keep up.

GPR55 receptors are numerous on osteoclasts and it appears that they can stimulate osteoclasts to break down bone. While this is a positive if it is kept below a certain threshold, if GPR55 stimulates osteoclasts too much, they can end up breaking down too much bone and osteoporosis can occur. If CBD or other cannabinoids can be used to block the action of the GPR55 receptor, and thereby prevent the overstimulation of osteoclasts, it could be considered a treatment for osteoporosis.

Now let’s look at how CBD may potentially help prevent cancer and or stop cancer from spreading by interacting with the GPR55 receptor. First, it is important to mention that the primary endogenous cannabinoid that interacts with the GPR55 receptor is a molecule called LPA which is the short abbreviation for the incredibly long tongue twister, lysophosphatidylinositol. Scientists have known for a long time that LPA levels are highly elevated in people who have cancer but they could not explain why this would be. Furthermore, these elevated levels of LPA are seen across many types of cancer… this fact made it more puzzling why this would be but also much more interesting. It appeared it had to be due to a factor that was common to several types of cancers.

It took a long time for scientists to figure out that the GPR55 receptor’s primary endogenous cannabinoid was LPA. However, once they did, they almost immediately suspected that the GPR55 receptor had something to do with the formation of cancer and in making cancer more invasive. In fact, experiments have now shown that if LPA is added to cancer cells, GPR55 receptors become more highly activated and cancer cells grow faster and become more invasive! So, it is thought that CBD and other cannabinoids that actually interact with the GPR55 receptor but act as an antagonist and block its action may be helpful in preventing cancer and in stopping the spread of cancer!

While more research needs to be done to fine tune these results and check them for accuracy, it appears across several studies that CBD and other antagonists to the GPR55 receptor could play a very important role in preventing diseases like osteoporosis and cancer and in healing these diseases once they have formed. With this in mind, we thought it was important that you be given information about GPR55 now so you can more fully understand the potential CBD has to prevent and cure disease…. and so you can be more alert in hearing about new research on the GPR55 receptor.

Keep in mind too that GPR55 may soon be officially named the third cannabinoid receptor, CB3, which will surely stimulate a lively discussion among everyone who takes CBD oil. Just remember where you heard about it first!