WEDNESDAY, March 15 (HealthSCOUT) -- Could keeping nicotine in the bloodstream actually help smokers quit?

The findings of a small study presented today at the annual meeting of the American Society for Clinical Pharmacology and Therapeutics in Los Angeles suggest that this unique approach may help wean smokers off cigarettes. Conventional stop-smoking methods reduce withdrawal symptoms by delivering nicotine via gum, patches or inhalers. The antidepressant drug Zyban is also approved for patients trying to quit smoking. Researchers from the University of Toronto have turned their attention to how the body metabolizes nicotine, focusing on an enzyme called cytochrome P450 2A6 (2A6, for short). This enzyme processes nicotine into its inactive byproduct cotinine and changes precancerous compounds in tobacco smoke into their cancerous forms. "When you block the enzyme, not only do you block the metabolism of nicotine, you also block the activation of these cancer-causing materials," says lead researcher Dr. Edward Sellers. Smokers unconsciously regulate how much they smoke to maintain a certain level of nicotine in their blood. Below that level, they get cravings, and above it, they get sick. "People adjust their smoking so they don't get so much nicotine on board, because if they do, they become nauseated and dizzy -- all the side effects of too much smoking that people are familiar with," says Sellers. Smokers couldn't smoke as much By inhibiting the 2A6 enzyme, Sellers believed he could slow the metabolism of nicotine and keep smokers in their optimal nicotine range longer. Since they wouldn't feel cravings, the smokers would take fewer or smaller puffs, or go longer between cigarettes -- possibly the first step toward quitting. For four days, Sellers, a professor of pharmacology and psychiatry, gave 11 smokers small doses of the psoriasis drug methoxsalen, which is known to inhibit 2A6. During that time, the patients showed higher levels of blood nicotine, and they also changed their smoking behavior. "Their smoking decreased by about 30 percent," says Sellers. Even though they had been told to continue smoking normally, he adds, "they weren't able to do that." Sellers also found lower levels of exhaled carbon monoxide -- a measure of smoke exposure -- and urine samples revealed that more of the toxic by-products of smoking were being expelled from their bodies. As well, says Sellers, "the [activation of precancerous material] was decreased by about 50 percent." That's important, he says, because "it's not the nicotine that's dangerous in cigarettes, it's the other things. It's the carcinogenic material that's in the smoke. "It has the potential to be very important, both as an approach to help people reduce and stop smoking, but also it may have potential to make smoking safer," says Sellers. "It would also be a way to augment the effectiveness of existing nicotine replacement therapies." Methoxsalen is not approved for use in smoking cessation. But Sellers says that very little of the drug gets into the bloodstream, meaning that internal organs and body tissues face very little exposure. However, extensive safety trials lie in the future. "In principle, it gives you a way to ease yourself out of tobacco dependence," says Jack Henningfield, an associate professor of psychiatry at Johns Hopkins Medical School in Baltimore. It may not be superior to conventional therapies, but it may help patients who aren't responding to gums or patches, says Henningfield. "Offering a greater range of treatments is really important." Also, says Henningfield, this may help people who are unable or unwilling to quit smoking. Right now, many try switching to "light" cigarettes, but Henningfield says there's no evidence that these cigarettes reduce their health risk. "Because the nicotine is reduced per puff, people take bigger puffs, more puffs, and get nearly as much smoke from the so-called light cigarette as they do from the regular cigarette." What To Do Ever wonder how many minutes of life you lose with each cigarette? Also, this HealthSCOUT story describes how new doctors aren't instructed on smoking cessation. Trying to quit smoking? Visit the Web sites for the Foundation for Innovations in Nicotine Dependence or QuitNet. You could also check out these tips from the American Cancer Society.

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