Can drastically reduced nicotine take the ‘hook’ out of cigarettes?

Finding a way to wean America’s 42.1 million adult smokers from their deadly habit is one of the great challenges in public health. But a new study offers hope that a trick proposed two decades ago — dialing back the nicotine that smokers get from their cigarettes — might help many quit, and steer others toward less dangerous means of feeding their addiction.

The new research, published Wednesday in the New England Journal of Medicine, also offers reassurance that smokers restricted to very low-nicotine cigarettes will not smoke more, nor inhale more deeply, to get the same addictive hit.

In an unusual clinical trial, longtime smokers who were assigned to smoke cigarettes with less than 15% of the nicotine in typical cigarettes saw their tobacco dependence drop by as much as 20% after six weeks.

Separately, smokers getting their usual dose of nicotine did not reduce the number of cigarettes they smoked daily. But those who got low-nicotine cigarettes smoked 23% to 33% fewer cigarettes daily, with “minimal evidence of withdrawal-related discomfort,” the researchers reported.

The fear that slashing cigarettes’ nicotine content would drive smokers into more dangerous habits has long discouraged U.S. health officials from rallying behind proposals to limit the amount of the chemical in combustible tobacco products.

That reluctance may be coming to an end.

A sweeping reduction of nicotine in smoked tobacco is “the most promising regulatory policy option” available for preventing the premature deaths of at least 20 million smokers, University of Wisconsin tobacco researchers Timothy Baker and Dr. Michael Fiore wrote in a commentary published with the study.

Such an initiative would need to cover all smoked tobacco products to ensure that people could not merely switch brands to get their fix, they wrote. And the research shows that nicotine limits need not be gradual to work, they added.

Smokers in the study weren’t told how much nicotine was in the cigarettes they received. However, many longtime smokers who got very-low-nicotine cigarettes suspected as much, said University of Pittsburgh psychologist Eric C. Donny, who led the study.

That wasn’t surprising, he said: In addition to its addictive properties, nicotine “contributes to that ‘hit’ in the back of the throat” when a smoker inhales.

What did surprise the researchers was that longtime smokers who got much smaller daily doses of nicotine than they were used to did not experience the harsh withdrawal symptoms — irritability, depressed mood, appetite changes — that cause many would-be quitters to turn back.

Donny invoked tobacco researcher Michael Russell’s 1976 observation that “people smoke for the nicotine, but they die from the tar.”

“That’s really at the heart of the matter,” Donny said. By finding a level of nicotine at which cigarettes lose their addictive hook, the research has gotten closer to “breaking the relationship between nicotine and this deadly product.”

In the trial, all 780 subjects acknowledged they had “no current interest in quitting” their smoking habit. Participants were randomly assigned to one of six groups. Five smoked study-provided cigarettes that ranged in nicotine strength from extremely low (0.4 milligrams per gram of tobacco) to levels more typical of cigarettes sold in the U.S (15.8 mg per gram). The sixth group continued to smoke their own brand of cigarettes.

Nearly 35% of those assigned to smoke very low-nicotine cigarettes for six weeks said they had tried to quit in the 30 days after the study ended. Among those who had continued to get their full fix of nicotine, 17% — roughly half as many — reported they had tried to quit.

When smokers completed two standardized surveys to gauge tobacco dependence, those who got the lowest doses of nicotine were judged significantly less addicted by both measures.

Anti-smoking activists were enthusiastic about the results.

“This is one of the most significant clinical studies related to tobacco done in decades,” said Matthew M. Myers, president of the Campaign for Tobacco-Free Kids. “This study not only demonstrates that it’s possible to reduce addictiveness, but provides solid evidence of the level of nicotine needed to accomplish that goal.”

The findings “should serve as a catalyst” for the Food and Drug Administration to consider limits on the nicotine content of smoked tobacco sold in the United States, he said.

In addition to loosening tobacco’s grip on the nearly 18% of American adults who smoke, a nicotine limit would make cigarettes far less addictive to the 3,200 American kids who try smoking for the first time on any given day, Myers said.

Others were more skeptical.

“I’m always surprised at how strict regulations appeal to public health activists,” said Jeff Stier, a senior fellow and risk analyst at the National Center for Public Policy Research, a free-market-oriented think tank in Washington. Advocates of such regulation are often quick to overlook the unintended consequences of such sweeping changes, including smokers’ efforts to circumvent the limits.

Experts said the FDA, which funded the trial, has the legal authority to order a sweeping reduction in the nicotine content of tobacco products on the U.S. market.

In drafting the Family Smoking Prevention and Tobacco Control Act of 2009, Congress prohibited the agency from lowering nicotine “yields” in cigarettes to zero. But the law allowed the FDA to “explore whether there is a level below which nicotine yields do not produce dependence,” and said the agency should make recommendations accordingly to the Department of Health and Human Services.

Whether the tobacco industry would let that happen without a fight remains to be seen.

Spokesmen for tobacco giants R.J. Reynolds Tobacco Co. and Altria Group, formerly known as Philip Morris Cos., said the companies were still reviewing the study.

“As the authors point out, a longer-term study is currently underway,” Altria spokesman Brian May in a statement provided to The Times. “Before establishing any regulations in this area, FDA will assess relevant science and evidence and solicit input on these topics from members of the public.”

In 1994, when tobacco researchers first proposed an FDA limit on nicotine strength, the industry reasserted its long-standing claims that the stimulant was not addictive. By 1995, however, an internal memo from Philip Morris came to light in which employees called cigarettes “nicotine delivery systems” and acknowledged that nicotine was the “primary reason” smokers kept coming back.

Myers, of the Campaign for Tobacco-Free Kids, said that the tobacco industry’s understanding of nicotine’s addictive power has been clear in its efforts to increase the doses that smokers get with their products. Over the years, he said, cigarette manufacturers have altered nicotine’s chemistry by adding ammonia, and manipulated how deeply consumers inhale tobacco smoke, all in an effort to increase the power of nicotine’s addictive hook.

“Policymakers … should take notice of this study,” said Dr. Sean P. David, a tobacco researcher and family physician at Stanford Medical School who was not involved in the current study.

David said the approach of “regulating the addictive potential out of combustible tobacco” is likely to prompt resistance from the tobacco industry and its allies in Congress. But findings like those published Wednesday should help public health officials “stand up to the tobacco industry lobby to clear the way for the FDA to use their statutory authority.”

Federal regulators may want to see more results before ordering industrywide nicotine limits on smoked tobacco, David said. But “many health policies have been implemented with much less data to back them,” including seat belt laws and more stringent policies against drunk driving.

“When so many people are dying from the results of smoking the most addictive drug known to man, a bias towards action seems well justified,” he said.

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