Smoking Behavior and Exposure to Tobacco Toxicants during 6 Months of Smoking Progressively Reduced Nicotine Content Cigarettes

Abstract

Background Recent federal legislation gives the FDA authority to regulate the nicotine content of cigarettes. A nationwide strategy for progressive reduction of the nicotine content of cigarettes is a potential way to reduce the addictiveness of cigarettes, to prevent new smokers from becoming addicted and to facilitate quitting in established smokers. We conducted a trial of progressive nicotine content tapering over 6 months to determine the effects on smoking behaviors and biomarkers of tobacco smoke exposure and cardiovascular effects. Methods 135 healthy smokers were randomly assigned to one of two groups. A research group smoked their usual brand of cigarettes followed by 5 types of research cigarettes with progressively lower nicotine content, each smoked for one month. A control group smoked their own brand of cigarettes for the same period of time. Results Nicotine intake, as indicated by plasma cotinine concentration, declined progressively as the nicotine content of cigarettes was reduced. Cigarette consumption and markers of exposure to carbon monoxide and polycyclic aromatic hydrocarbons, as well as cardiovascular biomarkers remained stable, while urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) excretion decreased. No significant changes in biomarkers of exposure or cardiovascular effects were observed in controls. Conclusions Our data support the proposition that the intake of nicotine from cigarettes of smokers can be substantially lowered without increasing exposure to other tobacco smoke toxins. Impact These findings support the feasibility and safety of gradual reduction of the nicotine content in cigarettes.

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

“…While transdermal nicotine helps some smokers quit (eg, Stead et al, 2008), most who use nicotine replacement therapies eventually relapse, partly because they miss the behavioral and sensory aspects of smoking (Rose et al, 2000). 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).…”

Nicotine Dependence, Nicotine Metabolism, and the Extent of Compensation in Response to Reduced Nicotine Content Cigarettes

“…We previously found that a reduction in nicotine content leads on average to minimal compensation and no increased exposure to tobacco smoke toxicants. 19,20 In this secondary analysis we analyzed baseline features of smoking to determine if they predicted those who responded differently to nicotine tapering in a 6-month study of nicotine reduction. We found that those with high nicotine dependence, as assessed by baseline FTCD, maintained differences in smoking behavior by smoking more cigarettes and exhibit greater smoke exposure (CO and PAHs) regardless of RNC level compared to those with low nicotine dependence.…”

“…Those who dropped out had a significantly higher level of dependence (FTCD). 19 It is possible that the dropouts tried to compensate for lower nicotine availability and were unsuccessful, leading to their dropping out. If so, the present analysis would underestimate the effect of dependence on compensation and does not identify the variables associated with this.…”

“…19 The study was a 2 year, two arm, randomized unblinded study in which smokers smoked their usual brand of cigarettes for a period of 2 weeks and then were randomly divided into a control group and a research group. The control group smoked their usual brand of cigarettes throughout the study.…”

“…19,20 We are unaware of studies that have examined whether individual factors such as nicotine dependence, genetic factors or rate of metabolism influence compensation when experiencing reduced nicotine availability. The present study addresses whether individual level predictors (i.e., nicotine dependence and rate of nicotine metabolism) influence smoking behavior, and tobacco smoke toxicant exposure in a reduced nicotine content cigarette trial.…”