Why Mapping The Receptor That Makes Weed Work Is A Big Deal

The malleability of the CB1 receptor is noteworthy for many different reasons.

News alert: People consume cannabis to feel things. Mostly, they're hoping to feel euphoria, decreased anxiety, hunger, or other happy side effects of being lit. But the reason weed makes anyone feel anything at all has to do with the cellular structures known as cannabinoid receptor 1 (usually referred to as CB1) in the human nervous system. Different plant cannabinoids such as THC stimulate that receptor, allowing us to experience all the feels. 

Writer Nick Stockton broke down the significance of the CB1 receptor in easily digestable language for Wired:

“Your body has CB1 receptors lacing the surfaces of cells in the brain, liver, lungs, fat, uterus, and sperm. . . CB1 receptors look like a bundle of microscopic sausage links. The sausages, seven in all, are spirals of amino acids that weave in and out of a cell's membrane. And they are very flexible. When a cannabinoid goes into the receptor, the sausage links—called helices—coalesce around that receptor's binding site. . . Never mind the lock and key: CB1 is like a door that opens to the tune of many different secret knocks.”

Basically, when THC enters the nervous system via weed smoke, vapor, cannabutter, etc., the CB1 receptor is turned on

Using X-ray crystallography––a favored molecular imaging technique of drug developers that shows a molecule’s structure in the form of a 3D crystal––Northeastern researcher Alexandros Makriyannis discovered that CB1, at the structural level, is actually quite malleable and can also be turned off.

“The structures reveal important insights into the activation mechanism of CB1 and provide a molecular basis for predicting the binding modes of delta9-THC, and endogenous and synthetic cannabinoids,” writes Makriyannis. 

He and his research team just published their findings in Nature on July 5.

“The crystallography revealed that two of the helices twisted and collapsed to fit around the molecule, shrinking the receptor to less than half its size when it received the off-switch molecule,” Wired reports on the findings.

This observed malleability is a noteworthy discovery because as legislation frees up access to marijuana research, cannabis-based medicinal treatments will be developed more frequently. And the ability to turn the receptor on and off via chemical activation might allow researchers to develop weed-based drugs with specific and targeted effects.