New Research on Why Nicotine Is Addictive

From the WebMD Archives

Reviewed by Dr. Dominique S. Walton

Nov. 16, 2000 -- Today's 24th annual Great American Smokeout, sponsored by the American Cancer Society, may entice some people to quit smoking. But many others will continue the deadly habit and not just because it's a habit, but because they enjoy smoking.

In fact, researchers have long known that the nicotine in cigarettes trips a pleasure center in our brains. Now, scientists also believe the drug imprints that enjoyment in people's memories, too, and this information may help researchers develop treatments to stop smoking.

This pleasure principle would explain why it's so difficult to stop smoking and why about 57 million Americans still light up cigarettes, according to the 1999 National Household Survey on Drug Abuse. The apparent physiological addiction leads to horrifying statistics: Tobacco use is responsible for almost one in five deaths in the U.S. annually, or more than 430,000, the American Cancer Society reports. Scientific evidence has linked smoking to almost all forms of cancer.

Researchers tell WebMD that knowing the molecule-triggering chemicals that generate pleasure and the ones that teach the brain to remember the enjoyment of nicotine will aid in finding new drugs to help people stop smoking.

"Addiction to nicotine is a complex sequence of events that causes the addictive behavior," says Daniel McGehee, PhD, a University of Chicago neurobiologist. He recently presented a paper showing that because nicotine triggers a memory mechanism in the brain called long-term potentiation (LTP), it reinforces the pleasant physiological effects of smoking. Though his research uses rats, he believes that the same cellular mechanisms are at work in people who smoke cigarettes.

"Showing that LTP activation by nicotine actually occurs in people is difficult, but from our research we can make strong inferences that it does," McGehee tells WebMD.

He says that if scientists can find a drug to block the nicotine-sensitive molecules and the ones that stimulate release of dopamine, a brain chemical that produces the pleasurable feelings, it could provide new ways to halt addictive behavior.

"I think there is a definite possibility of using [this information] to develop therapeutic drugs," says Edward Levin, PhD, a Duke University toxicologist and associate professor of psychology and behavioral science.


Levin and his colleague, Duke neuroscientist Jed Rose, PhD, co-inventor of the nicotine skin patch, have been investigating the use of the nicotine-blocking drug mecamylamine for smoking cessation.

Mecamylamine originally was used to treat high blood pressure. It prevents nicotine from fully activating the release of dopamine. Dopamine is activated not only by nicotine, but also by alcohol, cocaine, and even food. It causes a feeling of enjoyment. That pleasurable sensation is one of the factors leading to addiction.

Levin, Rose, and their colleagues found that using nicotine in combination with mecamylamine reduced the urge to smoke tobacco. In further studies, they discovered that when mice were given the same combination, it reduced the rodents' cocaine cravings -- by more than 40%.

Levin agrees with McGehee that it's a complicated formula because blocking nicotine molecules or stimulating release of dopamine can result in the release of a lot of different chemicals in the body.

Levin also cautions that while research has shown that nicotine can have beneficial effects, this is not an endorsement of smoking.

"Don't smoke, and don't use these nicotine remedies for anything other than cessation of smoking until all the research is done," Levin says.

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