A study on very-low-nicotine cigarettes released last week found smokers benefit more from an immediate, rather than gradual, reduction when it comes to risk exposure.

However, the overall results were mixed, the researchers found.

Smokers who experienced the immediate nicotine reduction levels “had lower toxicant exposure over time, smoked fewer cigarettes per day, had greater reduction in dependence, and more cigarette-free days.”

However, the study also found immediate nicotine reduction “caused greater withdrawal symptoms, greater use of non-study cigarettes and higher dropout rates.”

The study appeared in the Journal of the American Medical Association. Study participants were smokers who did not plan to quit their habit within a 30-day period.

Among the researchers is Eric Donny, who recently joined Wake Forest Baptist Medical Center as a professor of physiology and pharmacology in its Comprehensive Cancer Center.

The researchers’ main goal was trying to determine the optimal nicotine level in traditional menthol and non-menthol cigarettes that would produce minimal to no addiction. The lowest level in very-low-nicotine cigarettes typically is 0.4 milligrams.

“The primary goal for establishing a nicotine threshold for cigarettes would not be reducing smoking, but rather facilitating cessation of cigarettes as soon as possible, which would be achieved with the immediate reduction approach.”

On March 15, the Food and Drug Administration issued an advance notice of proposed rulemaking “to explore a product standard to lower nicotine in cigarettes to minimally or non-addictive levels.”

“This new regulatory step advances a comprehensive policy framework that we believe could help avoid millions of tobacco-related deaths across the country,” FDA Commissioner Scott Gottlieb said.

Analysts and advocates say the FDA notice kicked off a multi-year process that is likely to take many legal and regulatory twists and turns before any new regulations are established.

In the study, the risk measuring stick was reviewing biomarkers from smoke exposure.

The challenge with very-low-nicotine cigarettes has been making them appeal to smokers that are trying to wean themselves of cigarettes than can contain upward of 15.5 milligrams of nicotine.

Anti-smoking advocates have expressed concern that reducing nicotine levels too much could lead smokers to consume more cigarettes to get the same amount of nicotine, thereby increasing their exposure to carcinogens from the burning of the tobacco leaves.

The 120 study participants were separated into three groups, each over a 20-day period: those who only smoke a 0.4-milligram cigarette (likely made by 22nd Century Group, which has a manufacturing plant in Mocksville); a gradual reduction from 15.5 milligrams of nicotine to 11.7, 5.2, 2.3 and finally 0.4 milligrams; or continuing to smoke a 15.5-milligram cigarette.

“Immediate reduction of nicotine in cigarettes led to significantly greater decreases in biomarkers of smoke exposure across time, compared with a gradual reduction or a control group,” according to the report. “There were no significant differences between gradual reduction and the control.”

Researchers said study limitations included that the very-low-nicotine cigarettes were provided for free. “The effect that may occur when paying for these cigarettes is unclear,” researchers said.

22nd Century touted the study more proof

In June, 22nd Century Group said it had started three short-term studies on its very-low nicotine traditional cigarette products.

The three studies are focused on “investigating the behavioral and biochemical responses” to its Brand A product.

The goal is using the research to bolster its chances of gaining modified risk tobacco product status from the FDA. The company’s goal is submitting the application this year.

The modified-risk application will ask the FDA to approve a marketing order allowing 22nd Century to disclose to consumers that the Brand A cigarettes contains at least 95 percent less nicotine than the tobacco in conventional cigarettes.

“It is not at all surprising that removing, rather than gradually reducing, nicotine content in an experimental situation reduces biomarkers associated with smoking,” said David Sweanor, an adjunct law professor at the University of Ottawa and author of several e-cig and other tobacco and health studies.

“Just as an experiment that removed, rather than reduced, caffeine in coffee would be expected to reduce the biomarkers associated with coffee drinking.

“But such experiments are not likely to be indicative of what would happen in the real world if there was an attempt at cigarette prohibition by removing the psychoactive ingredient, just as there was an attempt at do with alcoholic beverages a century ago.:

Sweanor also said that “a bigger hurdle is that cigarette prohibition raises serious political issues (such as excise taxes) that are likely insurmountable until the tens of millions of people who smoke cigarettes have viable alternatives.”

“It is critically important that the FDA give equal priority to ensuring that users of cigarettes are provided with significantly lower risk tobacco and nicotine alternatives, and that the public receives truthful information about their lower risks,” said Scott Ballin, past chairman of the anti-smoking alliance Coalition of Science or Health.

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