Smoking Cessation: The Effect of Immediately vs Gradually Reducing Nicotine in Cigarettes


In March of this year, the FDA announced
that they were considering setting a standard for a maximum nicotine level in cigarettes to
make them minimally addictive or nonaddictive. JAMA this week is publishing a clinical trial
comparing two different approaches the FDA is considering for implementing
reduced nicotine cigarettes. T he first approach reduces nicotine
levels in cigarettes immediately, which might cause a significant number of
smokers to experience withdrawal symptoms and seek nicotine from other sources. The second reduces nicotine levels gradually,
which might result in prolonged exposure to smoke toxicants, compensatory smoking
during the early stages of nicotine reduction, and similar or even lower
smoking cessation rates. The objective of this study was
to compare the two approaches to assess differences in
biomarkers of smoke exposure. Researchers conducted a randomized
trial at 10 sites across the US. The participants were volunteers,
who were daily smokers with no intention to quit within 30 days. They had a mean age of 45 years. 701 were men, 549 were women. After 2 weeks of baseline smoking, the 1250
participants were randomized to three groups. The first group smoked lower
nicotine cigarettes for 20 weeks, where the nicotine was immediately reduced from the standard 15.5 mg to
0.4 mg per gram of tobacco. The second group also smoked lower
nicotine cigarettes for 20 weeks, but the nicotine was gradually reduced
every 4 weeks over the trial period from 15.5 mg to 0.4 mg per gram of tobacco. The third, or maintenance group,
continued smoking standard cigarettes with 15.5 mg of nicotine per gram of tobacco. The primary outcome was between-group
differences in biomarkers of smoke exposure over the 20 weeks of intervention. The biomarkers were: -breath carbon
monoxide -Urine phenanthrene tetraol, an indicator of exposure to polycyclic
aromatic hydrocarbons -and 3-HPMA, a volatile organic compound metabolite. Secondary outcomes included smoking
behaviors like cigarettes smoked per day, number of cigarette-free days, and
survey measures of nicotine dependence. Let’s review the results. 958 of the 1250 participants
completed the trial. Lower levels of exposure were
observed for all three biomarkers in the immediate nicotine
reduction group compared with the gradual nicotine reduction group. Lower levels of exposure were also observed in
the immediate nicotine reduction group compared with the control group for all three biomarkers. But no statistically significant
differences were observed between the gradual reduction group and the
control group for any of the biomarkers. In terms of the secondary outcomes, participants in the immediate nicotine reduction
group had fewer total cigarettes per day, a higher mean number of cigarette-free days, and
lower measures of nicotine dependence compared with those in the gradual
nicotine reduction group. The authors conclude that immediate
reduction in nicotine content of cigarettes provided the greatest reduction
in biomarkers of smoke exposure over time, and a reduction of cigarette consumption. However, they also note that immediate reduction
in nicotine caused greater withdrawal symptoms, greater use of nonstudy cigarettes,
and higher drop-out rates. One last thing. Our open access journal, JAMA Network
Open, recently published a study looking at how smoking reduced-nicotine
cigarettes affects smoking behaviors. The results of that trial also demonstrated
that replacing standard cigarettes with reduced-nicotine cigarettes did not
lead to an increase in smoking or exposure to the toxic components of cigarette smoke. The link to that study is
in the description below.