Drug That Curbs Nicotine Craving may do Same for Cocaine

Duke University Medical Center
Saturday, 8 April 2000

A drug that Duke University Medical Center researchers have successfully used to help some people quit smoking may also help curb cocaine cravings, according to studies conducted in rats.

The drug mecamylamine, used in combination with nicotine to help reduce the urge to smoke cigarettes, has now been shown in animal studies to reduce their self-administration of cocaine.

Rats that were trained to press a lever in order to get cocaine no longer pressed it with the same frequency after they were given mecamylamine, said Edward Levin, lead author of the study. Results were prepared for presentation Saturday by Tonya Mead and Amir Rezvani at the International Behavioral Neurosicence Society meeting.

When injected with mecamylamine, the mice infused cocaine 11 times per hour, versus 19 times per hour when they received a placebo injection of saline -- a reduction of more than 40 percent.

"It's always very exciting when a drug used for one addiction has implications for a broader range of addictive drugs," said Levin, whose study was funded by the National Institutes of Health.

Mecamylamine is an older medication originally used to treat high blood pressure. Researchers now know it blocks some of nicotine's ability, and potentially that of other drugs, to generate feelings of pleasure in the brain.

Levin said it works by occupying specific sites, called "nicotinic receptors," on nerve cells where nicotine would normally act. When mecamylamine blocks these receptors, nicotine can no longer exert its full action, that of stimulating the release of dopamine.

Dopamine is the primary brain chemical involved in generating pleasure. Drugs like nicotine, alcohol and cocaine all increase available amounts of dopamine and thereby increase the pleasure sensation, said Jed Rose, chief of the Nicotine Research Program at Duke and study co-author. Eventually, the brain may prefer the drug over natural rewards like food or sex, and hence, the person can become addicted.

Mecamylamine blocks the action of nicotine, and potentially cocaine, by lowering the net amount of dopamine available in the brain. While cocaine still boosts available levels of dopamine, its overall amount is decreased because mecamylamine has plugged up some of the nicotinic receptor sites where the brain would naturally be activating its own dopamine.

"In other words, the brain has its own chemical, acetylcholine, that stimulates the release of dopamine. Mecamylamine comes along and occupies some of the nicotinic acetylcholine receptor sites and prevents them from activating dopamine," Rose said. "So the net effect is that less dopamine is being produced, even when cocaine comes along and boosts dopamine levels through a different pathway."

Rose said the person still desires nicotine or cocaine, but the desire is weakened because the brain is no longer being flooded with dopamine.

"Mecamylamine reduces desire, but it doesn't quench it," he said. "Yet given how few medications there are to combat serious addictions, even a medication that reduces craving can be of significant benefit."

Already, mecamylamine has proven to be of significant benefit in helping people quit smoking. In earlier Duke studies, Rose demonstrated that using a patch with nicotine and mecamylamine together helped 40 percent of smokers quit for at least one year, while only 15 percent of smokers were able to do so using the patch alone.

The researchers expect mecamylamine to be approved for smoking cessation sometime this year.

For more information, or to contact Duke University Medical Center, see their website at: www.mc.duke.edu

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