An Aug. 17 commentary in the New England Journal of Medicine by Food and Drug Administration Commissioner Scott Gottlieb and Center for Tobacco Products Director Mitchell Zeller raises some concern about the agency’s new tobacco regulation strategy.

The piece touches on “less harmful tobacco products,” which Commissioner Gottlieb wrote favorably about earlier, but it includes descriptors—”potential” (four times) and “conceivable” (once)—that suggest the authors are not convinced e-cigarettes truly are lower-risk. Smokeless tobacco, already demonstrated to be vastly safer than cigarettes, isn’t mentioned.

In their commentary, the FDA officials advocate for radical nicotine reduction (RNR) in cigarettes.

RNR is a variation on a failed concept: supply-side elimination of popular products. Full-on cigarette prohibition was adopted, then jettisoned, in 12 states from 1899 to 1909. During Prohibition, a decade later, brewers tried to market an alcohol-free product called “near beer.” That bombed just as badly as Vector Group’s RNR cigarettes in 2003. Any new RNR products will likely be rejected as well, causing smokers to seek out higher-nicotine products, licit or otherwise.

Despite a significant expenditure of taxpayer dollars on RNR research, this approach has not been demonstrated to reduce adult smoking. For example, a $29 million clinical trial by Dr. Neal Benowitz, reported in 2015, produced dismal results.

The FDA commissioner and his co-author remain optimistic:

A recent 6-week study by Donny et al. showed that cigarettes with lower nicotine content reduced nicotine exposure and dependence, as well as the number of cigarettes smoked, as compared with cigarettes with standard nicotine levels.  

They are referring to another 2015 report, but that study’s results were unimpressive as well. Dr. Eric Donny recruited 840 smokers uninterested in quitting, and randomly provided them with one of seven types of cigarettes to use for six weeks: their usual brand, a full-nicotine study cigarette and five others with varying low-nicotine levels (2 percent to 33 percent of the full-nicotine cigarette). Subjects were paid up to $835 for 10 clinic visits, which probably contributed to a 92 percent completion rate.

While it was not surprising that smokers using reduced nicotine cigarettes had lower nicotine levels in their urine, most of the low-nicotine smokers (73 to 81 percent) admitted that they smoked three or four “wildcat” cigarettes (products not distributed as part of the study) on between 24 to 35 percent of the days in the trial.

There was little consistency regarding changes in dependence. On the Wisconsin scale, smokers in all groups had lower scores after six weeks than at baseline, with only one of the reduced nicotine groups significantly lower than the full-nicotine group. On the Fagerström scale, three low-nicotine groups were significantly lower than the full-nicotine group, but the changes from baseline were not impressive. In other words, it is not clear if the low-nicotine cigarettes reduced dependence.

The number of cigarettes smoked in the Donny study is interesting. At baseline, every group was smoking about 15 cigarettes per day. Although Gottlieb and Zeller imply that low-nicotine groups smoked fewer cigarettes at the end of the study, they actually averaged 15 to 16 cigarettes per day. Smokers of usual-brand and full-nicotine cigarettes smoked 21-22 per day after six weeks, an increase of 6-7. Perhaps Donny contributed to this increased consumption by providing full nicotine cigarettes for free.

Like the Benowitz study, the Donny study does not prove that reduced-nicotine cigarettes produce meaningful benefits for smokers. It also should be noted that the Donny study was supported by $93.3 million in grants from the National Institute on Drug Abuse and the FDA.

Image by Jurgis Mankauskas