Revealing How Marijuana Affects the Brain

A new imaging method could show how cannabinoids affect diseases like schizophrenia.

Scientists have long known that the brain possesses natural chemicals similar to marijuana. While little is known about their precise function in the brain, studies suggest that these compounds, known as cannabinoids, and the receptors they bind to, play a role in diseases, including schizophrenia, Parkinson's disease, and obesity.

Now researchers at Johns Hopkins University have developed a way to image cannabinoid receptors in living animals. The tool will help scientists figure out how these receptors are altered in drug addiction and disease, as well as helping pharmaceutical companies to design drugs that better target this system.

"This is a real breakthrough," says Richard Frank, vice president of medical affairs at GE Healthcare in Princeton, NJ. "Scientists have long believed that the cannabinoid system is involved in diseases, but they've never been able to measure the receptor in living people's brains." The tracer is very specific, and can therefore be used in low doses. That's important, says Frank, because the compound has no pharmacologic effect. In other words, it doesn't make the user feel "high."

Andrew Horti and Robert Dannals at Johns Hopkins designed a novel compound that selectively binds to the cannabinoid receptor, CB1, in the human brain, and labeled it with a radioactive tag. They then used imaging technology known as positron emission tomography (PET) to determine precisely where in the brain the receptors were present. "Such tracers offer the opportunity to study if receptors in the brain are static or if they increase or decrease when we're exposed to different substances [such as marijuana]," says Dannals, senior author on the study, whose results were presented at the Society of Nuclear Medicine meeting in San Diego last week. Such studies could give clues to addiction or other disorders.

Other such tracers exist for a myriad of brain receptors, including ones for opiates and serotonin, a neurotransmitter involved in depression. But creating an analogous molecule for cannabinoid receptors has been a challenge. Tracers are injected into a patient's bloodstream, where they travel to the brain and compete with naturally occurring chemicals for binding sites on the target receptors. But cannabinoid-like molecules are fat-soluble, meaning they're attracted to the lipid membranes of cells, and have trouble crossing the blood-brain barrier. (THC, the main active compound in marijuana, is an exception.) But Horti was able to design a molecule that could cross the blood-brain barrier and was highly specific to the CB1 receptor.