A synthetic form of marijuana's active ingredient kills pain by targeting the same pathway as morphine, researchers report tomorrow in Nature. The finding could lead to better treatments for chronic pain, if drug companies decide to develop the substance.
Opioids such as morphine work by targeting a brain region called the rostral ventromedial medulla (RVM). This region "acts like a volume control on a stereo--it can shut off the pain signal," says Ian Meng, a neuroscientist at the University of California, San Francisco. Previous work has shown that cannabinoids, the active ingredients in marijuana, are effective pain relievers, and Meng's group wondered if they also act on the RVM.
To find out, the researchers injected a synthetic cannabinoid into rats, then tried to counteract its effects with a compound that blocks neuron activity in the RVM. Rats given cannabinoids and the RVM blocker flicked their tails away from a heat source just as fast as the untreated rats, indicating that their pain perception had not been dulled, but the rats given just the cannabinoid took longer to move their tails away--indicating that the cannabinoids' analgesic effects depend on the RVM. By measuring activity of RVM neurons in anesthetized rats, the scientists confirmed that the cannabinoid targets the same pain-modulating neurons as morphine, but through a different mechanism. This suggests that cannabinoids might be useful for patients who have become tolerant of morphine.
Cannabinoids are an especially promising model for new drugs because unlike morphine, which can cause nausea and gastrointestinal problems, they stimulate the appetite, says neuroscientist Michael Walker of Brown University in Providence, Rhode Island. Any new drugs would be good news for cancer patients and other chronic pain sufferers who have trouble maintaining their weight. But politics are holding back development of new cannabinoids, says Walker: "Nobody wants to market a 'pot pill.' " Those attitudes may change. "There's a shift going on," says Walker, "and this paper adds to that."