Clinical & Trial Research on Medical Cannabis

The long march to credibility for cannabis research has been built on molecular biology. Smoking or otherwise consuming marijuana – Latin name Cannabis sativa – has a medical history that dates back thousands of years. But the euphoria-inducing component of cannabis, delta-9-tetrahydrocannabinol, or THC, wasn’t isolated until 1964, by biochemist Raphael Mechoulam, then of the Weizmann Institute of Science in Rehovot, Israel, and his colleagues. Within two decades, other researchers had developed synthetic THC to use in pill form. The secrets of how THC worked in the body lay hidden until the late 1980s, when researchers working with rats found that the compound binds to a protein that pops up on the surface of nerve cells. Further tests showed that THC also hooks up with another protein found elsewhere in the body. These receptor proteins were dubbed CB1 and CB2.

A bigger revelation came in 1992: Mammals make their own compound that binds to, and switches on, the CB1 receptor. Scientists named the compound anandamide. Researchers soon found its counterpart that binds mainly to the CB2 receptor, calling that one 2AG, for 2-arachidonyl glycerol. The body routinely makes these compounds, called endocannabinoids, and sends them into action as needed.

“At that point, this became a very, very respectable field,” says Mechoulam, now at Hebrew University of Jerusalem, who along with Pertwee and others reported the anandamide discovery in Science. “THC just mimics the effects of these compounds in our bodies,” Mechoulam says. Although the receptors are abundant, anandamide and 2AG are short-acting compounds, so their effects are fleeting.

In contrast, when a person consumes cannabis, a flood of THC molecules bind to thousands of CB1 and CB2 receptors, with longer-lasting effects. The binding triggers so many internal changes that, decades after the receptors’ discovery, scientists are still sorting out the effects. From a biological standpoint, smoking pot to get high is like starting up a semitruck just to listen to the radio. There’s a lot more going on.

Though the psychoactive effect of THC has slowed approval for cannabis-based drugs, the high might also have brought on a serendipitous discovery, says neurologist Ethan Russo, senior medical adviser for GW Pharmaceuticals, which is based in Porton Down, England. “How much longer would it have taken us to figure out the endocannabinoid system if cannabis didn’t happen to have these unusual effects on human physiology?”

Not just a high. By- Seppa, Nathan, Science News, 00368423, 6_19_2010, Vol. 177, Issue 13

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