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.).