United Press International - Wednesday, September 23, 1998
Lidia Wasowicz, UPI Science Writer

The University of California, San Francisco, study indicates the drug that mimics the principal active ingredient in pot has a morphine-like effect on the brain region that modulates pain.

The authors of the report, which will appear in the British journal Nature Thursday, say their finding points to the possibility of pot-like drugs being used as pain-killers.

Lead study author Ian Meng says opioids such as morphine provide strong analgesic effects for many types of pain -- but at a great price, producing such side effects as nausea and respiratory depression.

Marijuana, a type of cannabinoid drug, on the other hand, has the opposite effect, arousing appetite.

"In the future, it may be possible to use a lower dose of opioids if they are used in combination with a cannabinoid, producing fewer side effects and increasing the pain-relieving effects," Meng said.

The research centered on the brain region called the rostral ventromedial medulla, RVM, which modulates pain by either increasing or decreasing the amount of signals that pass through the spinal cord. They tested the effects of the synthetic cannabinoid, WIN555, 212-2, on this region by measuring the time it took for rats to move their tails away from a heat source.

In the first experiment, rats given the drug kept their tails on the heat source much longer than rats that were not.

"But after we shut down the RVM, rats that were given WIN55,212-2 no longer demonstrated insensitivity to pain, moving their tails from the heat source as quickly as the rats who had not received the drug," said Howard Fields, professor of neurology and physiology and research scientist in the W.M. Keck Foundation Center for Integrative Neuroscience at UCSF.

"The test demonstrated that the RVM was critical for producing the pain-relieving effects of cannabinoids."

In other experiments, the researchers made sure it wasn't the loss of coordination produced by the cannabinoid that was at work in the rats' tail action, said researcher William Martin.

"This experiment demonstrates that the rats given the cannabinoid did not leave their tails on the heat source simply because they had lost their motor coordination," said Meng. "The cannabinoid is also having an analgesic effect."

In analyzing the effect of cannabinoids on the activity of the brain cells called neurons in the RVM, the researchers determined that WIN55, 212-2 produced changes identical to those of morphine, said researcher Barton Manning.

But, they found, the changes were produced in different ways. A drug that blocks the effect of morphine was unable to prevent the effect of WIN55,212-2 and vice versa.

"These results indicate that the marijuana-like drug can reduce pain by affecting the same pain modulating neurons as morphine but through separate mechanisms," said Meng.

The study was funded by the National Institute of Drug Abuse, the UCSF Center for the Neurobiology of Addiction and the Canadian MRC.

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