Eliminating or significantly decreasing the use of combustible tobacco products would substantially reduce tobacco-caused morbidity and mortality (Zeller, Hatsukami, & Strategic Dialogue on Tobacco Harm Reduction Group, http://www.selleckchem.com/products/Roscovitine.html 2009). One way to achieve this goal is to reduce levels of nicotine in combusted tobacco products to nonreinforcing levels. Such reductions should not be driven by filter ventilation or other changes in cigarette design that can be easily countered by the user, but instead by reducing nicotine exposure. In this review, we emphasize reductions in the nicotine content of the tobacco itself below a threshold level of reinforcement, which would likely substantially decrease the development and level of tobacco dependence and facilitate cessation.

This is in contrast to approaches that set upper limits on machine-delivered nicotine yields but which were intended to remain capable of sustaining addiction (O��Connor, Cummings, Giovino, McNeill, & Kozlowski, 2006). In the United States, a nationwide gradual reduction of the nicotine content in cigarettes was proposed by Benowitz and Henningfield (1994) almost two decades ago. Subsequently, the conclusions by several predominantly U.S. researchers, organizations of scientists, and health professionals concurred that reduction of cigarette nicotine content to nonaddictive levels could have a significant and positive impact on public health (cf. American Medical Association, 1998; Gray et al., 2005; Henningfield et al., 1998; Tengs, Ahmad, Savage, Moore, & Gage, 2005; Zeller, Hatsukami, & Strategic Dialogue on Tobacco Harm Reduction Group, 2009).

With the enactment of the Family Smoking Prevention and Tobacco Control Act, the U.S. Food and Drug Administration (FDA) now has the authority to reduce nicotine to levels that are nonaddictive, although not to zero, if FDA concludes such a measure ��is appropriate for the protection of the public health.�� Similarly, the World Health Organization Framework Convention on Tobacco Control (FCTC) includes articles that allow governmental agencies to establish standards for nicotine. In meetings held in 2007 and 2009, scientists, tobacco control policy experts, and representatives of U.S. government agencies examined the scientific knowledge and feasibility of this approach. The scientific literature since 1994 was reviewed, presented, and discussed. Based on this discussion, the meeting participants came to the conclusion that actively pursuing research on nicotine reduction would be a highly worthwhile endeavor AV-951 (Hatsukami, Perkins, et al., 2010). The potential feasibility of this approach is particularly supported by studies conducted by Benowitz et al.