Studies Show Nicotine Reduction Reduces Smoking

The first large-scale clinical trial of very-low-nicotine cigarettes was a double-blind, randomized trial conducted between June 2013 and July 2014 at 10 sites in the United States. The article, which was published in the New England Journal of Medicine in October 2015, found that participants using low-nicotine cigarettes smoked nearly one-third fewer cigarettes a day and were twice as likely to try to quit, compared with smokers of regular cigarettes.

“If confirmed in longer-term studies, the findings suggest that, when combined with other tobacco-control policies (e.g., taxation and expanded access to treatment), limiting the nicotine content of cigarettes to reduce cigarette use and nicotine dependence and facilitate efforts to quit smoking could improve public health,” wrote lead author Eric Donny, Ph.D., a professor of psychology at the University of Pittsburgh, and colleagues.

To be eligible for the study, participants had to be age 18 years or older, smoke five or more cigarettes per day, and have no current interest in quitting smoking. Participants were randomly assigned to smoke for six 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 0.4 mg per gram of tobacco to 15.8 mg per gram of tobacco (typical of commercial brands).

A total of 840 participants underwent randomization, and 780 completed the six-week study. During week 6, the average number of cigarettes smoked per day was lower for participants randomly assigned to cigarettes containing 0.4 mg, 1.3 mg, or 2.4 mg of nicotine per gram of tobacco (14.9, 16.3, and 16.5, 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).

Dependence, as assessed by the Wisconsin Inventory of Smoking Dependence Motives, was also found to be significantly lower at week 6 among participants smoking cigarettes with 0.4 mg of nicotine per gram compared with those smoking cigarettes with 15.8 mg of nicotine per gram.

Because smokers with elevated depressive symptoms have relatively poor responses to smoking cessation treatments, some people have voiced concern that these smokers could experience unintended negative consequences if the FDA were to significantly cut nicotine levels. A study published in Nicotine and Tobacco Research in 2016 found that the effects of low-nicotine cigarettes are similar regardless of whether smokers have elevated depressive symptoms or not.

“Reducing the nicotine content of cigarettes below an addiction threshold appears to be a potential avenue for reducing cigarette dependence, which may improve responses of these smokers to other public health approaches and smoking cessation treatments,” wrote lead author Jennifer Tidey, Ph.D., a professor of psychiatry and human behavior at Brown University.

For this secondary analysis of the 2015 NEJM study, researchers used linear regression to determine whether baseline depressive symptom severity (scores on the Center for Epidemiologic Studies Depression Scale [CES-D]) moderated the effects of reduced-nicotine-content cigarettes, compared with regular-nicotine-content cigarettes, on smoking rates, depressive symptom severity, and related subjective and physiological measures.

Of the 717 participants included in the analyses, 109 (15 percent) had CES-D scores of greater than or equal to 16 (indicating possible clinical depression), and 608 (84.8 percent) had CES-D scores of less than 16.

Regardless of baseline depressive symptoms, participants randomized to reduced-nicotine cigarettes had lower smoking rates, nicotine intake, nicotine dependence, and cravings at week 6 than those assigned to regular nicotine cigarettes. In participants with higher baseline depressive symptoms, those assigned to reduced-nicotine cigarettes had lower week 6 depressive symptoms than those assigned to regular nicotine cigarettes.

The study by Tidey and colleagues was funded by the National Institutes of Health and the Food and Drug Administration (FDA) Center for Tobacco Products. The study by Donny and colleagues was supported by the National Institute on Drug Abuse and the FDA Center for Tobacco Products. ■