Commentary on Hatsukami et al. (2010): Building the science base for tobacco product regulation—nicotine reduction


Fifteen years ago, Neal Benowitz & Jack Henningfield proposed that the population could be weaned from tobacco addiction by radically reducing the nicotine delivery of cigarettes [1]. The study by Hatsukami and colleagues represents an important—and promising—early ‘read’ on the effects of nicotine reduction to prevent addiction and promote cessation [2].

Although the study is preliminary, it helps to inform scientifically the proposed policy of reducing tobacco dependence by reducing the nicotine delivery of cigarettes. Fortunately, the regulatory tools to implement such a policy now exist—although at the right time and with a sufficiently robust evidence base. Globally, Articles 9–11 of the Framework Convention on Tobacco Control provide the authority for countries that have signed and ratified the Convention to explore such a policy. The United States, although it has not yet ratified the Convention, recently passed into law the Family Smoking Prevention and Tobacco Control Act [3]. Section 907 of this new law empowers the US Food and Drug Administration (FDA) to use ‘product standards’ to reduce the level of nicotine in tobacco products to non-addictive levels, as long as FDA does not completely eliminate nicotine.

From a policy perspective, a science-based nicotine reduction strategy has tremendous appeal. Imagine a world where the only tobacco products that young people will inevitably experiment with were not capable of creating and sustaining addiction. In that same world, imagine a comprehensive nicotine regulation policy that shifted tobacco users down the ‘continuum of risk’ from the most dangerous form of nicotine delivery (cigarettes) to the least risky (therapeutic nicotine products) [4].

The Hatsukami study is encouraging, because it suggests the potential for such a policy. At the same time, it reminds us how far the science has to go to match up to the aspirations of a broad, bold national nicotine reduction policy. In the study, 32 smokers smoked ultra-low nicotine cigarettes for 6 weeks. These smokers were volunteers, from a starting pool of almost 10 times as large who were interested in quitting, and were paid for participating in what they knew was a time-limited experiment. In contrast, implementing nicotine reduction as a national policy would entail imposing such modified cigarettes, in perpetuity and universally, on a heterogeneous population of 45 million smokers, many of whom are not ready to quit and may not support a nicotine-reduction policy.

As Hatsukami and colleagues note, one of the biggest concerns about nicotine reduction is compensation: the possibility that smokers would try to counteract nicotine reductions by smoking more or smoking harder, possibly nullifying any beneficial effects of nicotine reduction, and actually increasing their exposure to tobacco toxicants. The study results give some reason for optimism in that they show that this did not occur in this small-scale limited test; but it is difficult to extrapolate from this to population behavior. Might some smokers make herculean efforts to compensate and thereby be harmed? Might ways be found to defeat the technical limitations of the re-engineered products? (One is reminded of the opiate formulations designed to minimize abuse which, subjected to the desperately creative efforts of drug users, proved to be eminently abusable.) How will nicotine reduction play out in an open market?

Studies such as this one cannot answer these questions. They are but the first step in exploring how nicotine reduction might affect smokers. Their encouraging findings need to be followed-up in larger, more varied and more ecologically valid studies before we can be confident in the effects of a nicotine reduction policy. Furthermore, regulatory agencies would need to know what the threshold level of nicotine is at which addiction is substantially eliminated, so that a proper reduction strategy can be devised.

At a forum on tobacco, David Kessler, the former US FDA Commissioner who started the agency on the road to tobacco regulation, suggested that the purpose of regulation is to encourage research. Certainly in this instance, the need for science-based regulation should drive research into the population-level effects of a nicotine reduction policy. One need only recall the now-haunting words of a tobacco industry executive in 1963, who said that ‘Nicotine is addictive. We are, then, in the business of selling nicotine—an addictive drug’[5]. Regulators and researchers need to redouble efforts to provide the evidence base and resulting policy that will prevent condemning yet another generation of tobacco users to premature death and disease that is principally a function of a life-long addiction to an inherently dangerous product.

Declarations of interest

Both authors are affiliated with Pinney Associates, which provides consulting services to GlaxoSmithKline Consumer Healthcare on issues related to treating tobacco dependence.