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@NEJM Ask the Authors & Experts: Randomized Trial of Reduced-Nicotine Standards for Cigarettes & A Promising Regulatory Pathway

Special Article

Randomized Trial of Reduced-Nicotine Standards for Cigarettes

Background

The Food and Drug Administration can set standards that reduce the nicotine content of cigarettes.

Methods

We conducted a double-blind, parallel, randomized clinical trial between June 2013 and July 2014 at 10 sites. Eligibility criteria included an age of 18 years or older, smoking of five or more cigarettes per day, and no current interest in quitting smoking. Participants were randomly assigned to smoke for 6 weeks either their usual brand of cigarettes or one of six types of investigational cigarettes, provided free. The investigational cigarettes had nicotine content ranging from 15.8 mg per gram of tobacco (typical of commercial brands) to 0.4 mg per gram. The primary outcome was the number of cigarettes smoked per day during week 6.

Results

A total of 840 participants underwent randomization, and 780 completed the 6-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 2.4, 1.3, or 0.4 mg of nicotine per gram of tobacco (16.5, 16.3, and 14.9 cigarettes, respectively) than for participants randomly assigned to their usual brand or to cigarettes containing 15.8 mg per gram (22.2 and 21.3 cigarettes, respectively; P<0.001). Participants assigned to cigarettes with 5.2 mg per gram smoked an average of 20.8 cigarettes per day, which did not differ significantly from the average number among those who smoked control cigarettes. Cigarettes with lower nicotine content, as compared with control cigarettes, reduced exposure to and dependence on nicotine, as well as craving during abstinence from smoking, without significantly increasing the expired carbon monoxide level or total puff volume, suggesting minimal compensation. Adverse events were generally mild and similar among groups.

Conclusions

In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. (Funded by the National Institute on Drug Abuse and the Food and Drug Administration Center for Tobacco Products; ClinicalTrials.gov number, NCT01681875.)

Perspective

Reduced-Nicotine Cigarettes — A Promising Regulatory Pathway

Excerpt

In 1976, tobacco researcher Michael Russell wrote that “People smoke for the nicotine but they die from the tar”1 — suggesting a potential regulatory pathway for eliminating the key harms arising from tobacco use. That is, by reducing or eliminating nicotine from combustible-tobacco products, we might be able to dramatically reduce their use and smokers' dependence on them, averting the harm they caused.

More than 30 years later, in June 2009, President Barack Obama signed legislation that permits the reduction of levels of nicotine, tobacco's primary addictive agent. Section 917 of the Family Smoking Prevention and Tobacco Control Act states that the Tobacco Products Scientific Advisory Committee of the Food and Drug Administration (FDA) shall provide advice, information, and recommendations to the secretary of health and human services on several issues, including “the effects of the alteration of the nicotine yields from tobacco products” and “whether there is a threshold level below which nicotine yields do not produce dependence on the tobacco product involved.” The legislation also contains a provision that prohibits the FDA from “requiring the reduction of nicotine yields of a tobacco product to zero.”