Randomized Trial of Reduced-Nicotine Standards for Cigarettes

Abstract

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.)

Reduced-Nicotine Cigarettes in Young Smokers: Impact of Nicotine Metabolism on Nicotine Dose Effects

“…Smoking cigarettes that deliver less than conventional doses of nicotine (ie,~1 mg/cigarette) reduce nicotine dependence (Benowitz et al, 2007;Benowitz et al, 2012;Benowitz et al, 2015) and promote smoking cessation when used with transdermal nicotine (Hatsukami et al, 2013). Further, a trial of reduced-nicotine cigarettes delivering~0.05-1.2 mg nicotine in 780 smokers showed decreases in nicotine dependence and cigarette consumption at 6 weeks compared to baseline (Donny et al, 2015).…”

Commentary on Nardone et al. (2016): Satisfaction, dissatisfaction and complicating the nicotine‐reduction strategy with more nicotine

“…Nardone et al [1] extend a previous publication [2] by reporting that lower 'satisfaction' from very low nicotine cigarettes (VLNC) predicts non-compliance with VLNC. While only 39% of participants reported non-compliance, a new objective measure indicates that 78% were probably smoking other cigarettes.…”

“…Mixing more satisfying nicotine products with fully toxic, less satisfying low nicotine cigarettes will probably influence net satisfaction, longevity of their use and health effects.Nardone et al[1] extend a previous publication [2] by reporting that lower 'satisfaction' from very low nicotine cigarettes (VLNC) predicts non-compliance with VLNC. While only 39% of participants reported non-compliance, a new objective measure indicates that 78% were probably smoking other cigarettes.…”

Let actual markets help assess the worth of optional very-low-nicotine cigarettes before deciding on mandatory regulations

“…[2,3]). The strategy proposes that, for the good of public health, the only cigarettes that should be sold legally must contain such low levels of nicotine in the tobacco that they would not create or support addiction.…”

“…The FDA has become the major funder of tobacco research in the United States, devoting tens of millions of dollars to pursuing the strategy. What has been viewed as the best study to date was published recently to much acclaim [2]. The World Health Organization's (WHO) TogReg committee has advised that such a strategy should eventually become an element of tobacco control [5].…”