A study published this summer provides a fundamental framework that shows exactly how part of the human nervous system, specifically CB1 receptors, react to active chemicals in marijuana, paving the way for new drug discovery.
The human endocannabinoid system is a series of nerve cell receptors designed to receive neurotransmitter molecules, working like locks and keys to initiate a cascade of physiological functions that regulate mood, appetite, memory, sleep and a host of other functions.
Alexandros Makriyannis, director of Northeastern University’s Center for Drug Discovery, and his team of researchers decided they wanted to map one type of cannabinoid receptor called CB1 to figure out exactly how it works. CB1 is the “lock” which interacts with Delta-9 Tetrahydrocannabinol (THC) and other cannabinoids in marijuana and produced naturally by the body.
Based on the Northeastern team’s research, however, that “lock-and-key” metaphor is inadequate. When the team examined samples of CB1 in different states of activation with THC and other chemical variants, the team found the CB1 opening stretches and collapses to fit different sizes and shapes of molecules.
Meaning instead of a lock, the the CB1 receptor is more like the mouth of a drawstring bag, and different parts of different transmitter molecules like THC actively cause the drawstring to constrict or expand. The receptor, it appears, has molecular toggle switches that control this behavior based how the transmitter molecules interact with them.
This means drugmakers could target the CB1 receptors with a much wider range of drug molecules that they thought possible before, leading to all sorts of potential to control and treat a host of physical and psychological disorders.
This opens the door not only for different kinds of marijuana-based medicines but also synthetic medicines that have wildly different effects and benefits. In the course of the Northeastern team’s research, they even found a CB1 antagonist, meaning a chemical that turns off the CB1 receptor instead of activating it. This could be useful for users in need of “coming down” from an extreme high. Cannabidiol (CBD) may also be able to provide insights to this function of CB1 receptors, as it has classically been used to help weed anxiety.
Scientists were able to figure out these properties through a process called X-ray crystallography. This is a method used to find the shape of molecules in a wide variety of materials — it’s how researchers discovered the double-helix shape of DNA, for example.
Molecules are too small to see under a microscope, so scientists replicate the molecules under study in repeating, crystalline pattern, then shoot an X-ray through the material at a sensor. Based on the frequency at which the X-rays bounce off the structure, the scientists can mathematically figure out the shape of the molecules by crunching the data.
REFERENCES FOR CB1 RECEPTORS:
“Crystal structures of agonist-bound human cannabinoid receptor CB1”
Tian Hua, Kiran Vemuri, et al
“Scientists Map the Receptor that Makes Weed Work”
July 6, 2017