Scientists have known for quite some time why marijuana makes you high, but not how.
A specific compound in the plant interacts with a specific receptor in the brain, and there are psychoactive effects as a result (that is, making you feel high). What has baffled the scientific community, though, is precisely how this interaction works.
The biggest problem has been that the receptor in question is highly volatile, so studying its structure, and thus how it works, has been challenging.
A new study published in the journal Cell explains how this group of researchers has overcome that problem: by freezing the receptor.
Your Brain’s Cannabis Receptor
Many readers may already be familiar with the compound in marijuana that is responsible for its many side effects. It’s called THC, or delta 9 tetrahydrocannabinol.
Being under its influence is what’s responsible for the euphoria, relaxation, appetite stimulation, and everything else associated with marijuana.
What fewer may know is what that THC does when it enters the body. The compound interacts with a brain receptor called CB1. Like other receptors, CB1 doesn’t have only one function.
It’s responsible for a broad range of things, some of which are pain relief, appetite suppression, and mood regulation. In other words, CB1 isn’t there just to accept THC; its role in your everyday life, even without marijuana, is crucial.
Given the many things CB1 can do to the body, knowing that THC binds to it to cause its psychoactive effects doesn’t tell us a whole lot about how it works.
After all, other substances that also bind to the CB1 receptor have produced wildly different results. Take “K2, or “spice,” for example.
It’s marketed and sold as ‘synthetic marijuana.’ While it does bind to the same receptor in the brain, its effects are much more dangerous.
Many have been hospitalized for chest pain, vomiting, high blood pressure, tremors, seizures, and hallucinations as a result of its use. So what makes K2 and marijuana produce such startlingly different responses?
Clearly, the answer’s in the way they interact with the CB1 receptor. And now that we can study the receptor’s structure, we may be uncovering that answer sooner rather than later.
Scientists Freeze The Receptor To Study Its Structure
Typically, researchers will use chemicals to extract a receptor-like CB1 to examine it and map out its structure. CB1 specifically, however, proved too unstable for this process.
The chemicals used for extraction damaged the receptor, and that made mapping its structure impossible. Without knowing what the receptor looks like, understanding how cannabis, K2, or anything else exerts its influence on it was a mystery.
Co-author of the study Alexandros Makriyannis found a solution. He created a molecule that would freeze the receptor for just long enough to map it out. Once they did that, the team made an exciting discovery: CB1 has a lot more “active sites” than they thought.
An active site is a unique place in the receptor that allows it to be ‘turned on.’ In the case of CB1, there are many of these sites within it, allowing for an outside compound to activate some parts of the receptor, but not others.
This would account for why K2 and cannabis produce such differing results: they are turning on different active sites within the same receptor.
To study the effects of THC on CB1, the team has begun doing computer simulations. By inputting the structure of both the compound and the receptor into the program, the researchers are starting to see how the two interact.
While important, they add that simulations are no replacement for seeing the actual interaction and that further studies should be done.
The Final Hit
Understanding which active sites in CB1 a particular compound like THC is engaging is a huge step forward. Having the schematic to the receptor also allows us the opportunity to create our own molecules as medication. These can be tailor-made to hit the ‘appetite stimulation’ site without the ‘paranoia’ site, for example.
And, of course, the additional benefit of further understanding how marijuana interacts with the body cannot be understated. The authors of the study have received a grant from the National Institutes of Health to continue their work. Through their observations, there are no doubt more exciting discoveries to come.