While researchers have long known that one of the active component in cannabis – known as tetrahydrocannabinol (THC) – acts on the cannabinoid receptors in the brain, the mechanisms behind this interaction were previously unknown. Now, researchers have uncovered the structure of the cannabinoid receptor 1 (CB1), in a study which was published in the journal Cell.
Using this crystal structure, the researchers were able to create a 3-D model of the CB1 receptor. According to the researchers, having a better understanding of how THC and synthetic cannabinoids interact with the receptor could help uncover some of the benefits and risks of cannabis use.
“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,” said co-author Raymond Stevens, a professor of Biological Science and Chemistry at the University of Southern California, “especially since we’re starting to see people show up in emergency rooms when they use synthetic cannabinoids.”
According to the researchers, it’s unknown why THC derived from Cannabis sativa has such a high safety margin, compared to synthetic cannabinoids which can cause serious side effects in certain doses. Their research on the structure of CB1 could help drugmakers design safer therapeutics capable of acting on the receptor.
By synthesizing a synthetic cannabinoid known as AM6538, Stevens and his team were able to determine the conformation of the CB1 receptor. When studying the 3-D model of the CB1 receptor, the researchers identified multiple regions which may explain how THC and synthetic cannabinoids produce psychoactive effects on the body.
“Researchers are fascinated by how you can make changes in THC or synthetic cannabinoids and have such different effects,” said 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.”