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Medicine | IN THE LAB

Quitting for good

A new drug that appears to reduce nicotine's pleasure factor may help smokers break the habit without relapsing, according to a study.

October 20, 2003|Shari Roan | Times Staff Writer

Smokers who want to quit can find plenty of help -- from behavioral counseling to nicotine patches and gum to the smoking-cessation pill Zyban -- but those aids don't work for everyone.

Seventy percent of smokers say they would like to break the habit, according to the Centers for Disease Control and Prevention. But, in a study of Wisconsin smokers published earlier this year, 70% of smokers said they had tried to quit one to five times; most relapsed within a week.

A new medication could help even those who find it particularly difficult to quit. The drug, varenicline, attempts to shorten the road to quitting by targeting the specific mechanisms in the brain involved in nicotine addiction. When smokers inhale, nicotine reaches the brain within 10 seconds and binds to nicotine receptors.

"This creates a powerful sense of satisfaction," says Dr. Karen Reeves, executive director of manufacturer Pfizer's global research and development program. "But the initial effect recedes quickly and a cycle of craving ensues, which is why people go back to the next cigarette. And it's why it's so difficult to stop smoking."

In a small, seven-week study comparing the new drug with Zyban and a placebo, 48% of smokers taking varenicline were able to quit smoking. In contrast, 33% of smokers taking Zyban were able to quit; 16% of those taking a placebo kicked the habit. None of the participants knew which pill they were taking.

Now the pill has been ushered into a larger, international study to corroborate the effects seen in the earlier study. The pharmaceutical firm is keeping many of the details about the first study and the larger one under tight wraps. A company spokeswoman would only say that "several hundred" smokers participated in the earlier study. The company would not release the number of smokers or study sites in the larger study underway.

"Smoking is a chronic, relapsing medical illness and not a lifestyle choice," Reeves says. "When people try to quit on their own, only 2% to 5% succeed. People usually have to try multiple times to quit before they're successful."

Varenicline activates the nicotine receptors in the brain, altering the normal response to the substance. It does this in two ways, by allowing the brain to think the nicotine has arrived, thus satisfying the craving, but by not being pleasurable enough to contribute to craving and addiction.

Nicotine delivered via cigarette acts like a 100-watt lightbulb in the receptor, Reeves says, but varenicline acts like a 50-watt bulb in the same receptor.

Researchers say the drug's biggest advantage may be in its ability to soften the blow of a relapse.

"If the smoker lapses and smokes a cigarette, varenicline has the potential to diminish the sense of satisfaction associated with smoking," she says. "This is likely to prevent a lapse from turning into a full-blown relapse."

The work on varenicline emerged from work performed several decades ago by scientists in the Soviet Union. The scientists discovered that a chemical called cytisine, which is found in many plants, seemed to help smokers quit, and they suspected that it partly blocked the nicotine receptors in the brain.

Although cytisine proved unsatisfactory because its effects are short-lived, varenicline could be headed for the marketplace. If that happens, it would be the first drug created specifically for smoking cessation. Zyban (bupropion) emerged as an anti-smoking treatment after first being sold, under a different name, as an antidepressant.

The continuing studies on varenicline will explore dosage, possible side effects and how to best use the medication. Varenicline did not cause any serious side effects in the early studies, Reeves says.

Doctors who help smokers with cessation are anxious to see published data on the varenicline studies, something that is unavailable so far, says Dr. Michael Fiore, director of the University of Wisconsin Center for Tobacco Research and Intervention.

Zyban and varenicline -- if varenicline eventually proves to be safe and effective -- offer hope to smokers, he said, because they work on such a primary level, targeting areas of the brain involved in addiction. Zyban appears to help smokers by raising levels of the brain chemical dopamine that decline when people smoke.

Fiore says smokers need not wait for the emergence of a new medication to give up their habit.

"It is a great time for smokers to quit," Fiore says. "There are options out there. The days of quitting cold turkey are over."

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