Study in Futility: Reduced-Nicotine Testing Way Too Short

NICOTINE & HEALTHA new study in the New England Journal of Medicine suggests that near-complete elimination of nicotine from cigarettes might lead to declines in smoking, but its brief duration could not possibly show anything relevant to real-world smoking issues.

The study, "Randomized Trial of Reduced-Nicotine Standards for Cigarettes," was carried out in 10 locations from mid-2013 through mid-2014 and led by Eric C. Donny, Ph.D., from the University of Pittsburgh, along with a host of tobacco researchers from the other nine institutions.

The 840 volunteer subjects were all smokers of at least five cigarettes per day, and none planned to quit smoking within the next month. They were randomly assigned to smoke either their regular brand, an "investigational" brand with nicotine level typical for most cigarettes, or one of six reduced-nicotine-level brands.

All cigarettes were supplied free of charge. The trial lasted six weeks, and the subjects were asked at several points during the study as to how many cigarettes they smoked and also as to their experience with withdrawal symptoms, if any. The lowest level of nicotine in the experimental brands was a minuscule 0.4 mg per gram of tobacco, while the highest level was 15.8 mg per gram of tobacco, a level representative of most cigarettes on the market.

The authors reported that when nicotine levels were reduced to 5.2 mg, there was no change in smoking behaviors. However, when the level was reduced to 2.4, 1.3 or 0.4 mg per gram of tobacco, the subject-smokers had about a 23 percent reduction in the number of cigarettes smoked per day. The low-nicotine smokers also reported less intense craving and withdrawal symptoms. And when asked 30 days after the study ended, those smokers on the lowest level of nicotine reported a higher rate of attempting to quit altogether (35 percent to 17 percent in the higher nicotine groups).

In an accompanying editorial Dr. Michael Fiore and Timothy Baker try to use it as a foundation for a new FDA regulatory paradigm, i.e., mandating severe reductions in nicotine in all cigarettes as a path toward reducing the toll of cigarette smoking.

That doesn't follow due to the limited duration of the study, and the concern about using it to create a new policy was voiced by Dr. Norman Edelman, senior scientific advisor for the American Lung Association, who was not involved in the research. "Whether you can leap from this [study] to a new policy is kind of problematic," he told Reuters. "The study was only six weeks. In the smoking cessation business, we don't even look at a six-week study. Six months or a year is the real test of whether an intervention is effective or not."

This is not the first time reduced nicotine cigarettes have been considered by tobacco and addiction experts, and discarded pretty much altogether. The danger of reducing nicotine levels has always been that such a move might provoke smokers to smoke more and/or inhale more deeply to get their craved nicotine, which would, of course, increase their toxic exposures to the lethal tar and gaseous ingredients in the smoke. Even a prior proponent of reducing nicotine, Dr. Neal Benowitz, has only recently (July 2015 in the journal Addiction) published a study which seemed to quash this approach: "Low-nicotine cigarettes fail to sway smokers."

As Dr. Edelman noted, six weeks is too short a time when assessing smoking issues. Six months is a minimum, as any smoker who's "quit" for a few weeks will tell you.

More information on the effects of nicotine on health can be obtained from ACSH's publication, here.