Researchers Unveil 3-D Image of ‘Marijuana Receptor’

By Pat Anson, Editor

An international team of researchers has released the first three-dimensional image of a human cannabinoid receptor – a discovery expected to advance research into the medical and recreational use of marijuana.

The research findings, published in the journal Cell, focused on how tetrahydrocannabinol (THC) -- the chemical in marijuana that makes people “high” -- binds to a cannabinoid receptor known as CB1, which is embedded in the surface of many nerve cells.

Cannabinoid receptors are part of a large class of receptors known as G protein-coupled receptors (GPCR), which account for about 40 percent of all prescription pharmaceuticals on the market.

"As marijuana continues to become more common in society, it is critical that we understand how it works in the human body," said Zhi-Jie Liu, a professor and deputy director of the iHuman Institute at Shanghai Tech University, who is also affiliated with the Chinese Academy of Sciences.

"We need to understand how marijuana works in our bodies; it can have both therapeutic potential and recreational use, but cannabinoids can also be very dangerous."

At the beginning of the study, researchers struggled to collect enough data to produce a crystal form of the CB1 receptor, which was needed to create the high-resolution image.

When they finally succeeded in crystalizing the receptor, they found a complex structure of pockets and channels to various regions of the receptor.

The discovery could help explain why synthetic marijuana and medicines designed to mimic cannabis have had unexpected and sometimes harmful side effects.

For example, a cannabis-based drug developed to treat obesity was found to cause depression, anxiety, and suicidal tendencies, so the medication was pulled off the market.

And synthetic marijuana, such as Spice and K2, can have severe side effects such as seizures, hallucinations, anxiety attacks and even death.  

Yekaterina Kadyshevskaya, Stevens Laboratory, USC

Yekaterina Kadyshevskaya, Stevens Laboratory, USC

"With marijuana becoming more popular with legislation in the United States, we need to understand how molecules like THC and the synthetic cannabinoids interact with the receptor, especially since we're starting to see people show up in emergency rooms when they use synthetic cannabinoids," said study co-author Raymond Stevens, a professor at the iHuman Institute and a professor of Biological Science and Chemistry at the University of Southern California.

The findings could also guide the development of cannabis-based drugs to treat pain, inflammation, obesity, fibrosis and other medical conditions.

"Researchers are fascinated by how you can make changes in THC or synthetic cannabinoids and have such different effects," says Stevens. "Now that we finally have the structure of CB1, we can start to understand how these changes to the drug structure can affect the receptor."