Even if a product could indeed be shown to be safe(r), the www.selleckchem.com/products/tofacitinib-cp-690550.html potential for large increases in usage could actually produce net harm to the population if significant numbers of smokers use it. Some tobacco control advocates have pointed to Sweden, where cessation (Furberg et al., 2005, 2007) and smoking mortality (Foulds, Ramstrom, Burke, & Fagerstrom, 2003) have been linked to increases in smokeless tobacco use, as evidence that smokeless tobacco could promote public health among smokers. Others doubt that the Swedish experience could translate to U.S. smokers (Zhu et al., 2009). Clearly, more research is needed to determine (a) if and how smokers use smokeless tobacco in the real world, (b) the long-term impact of such usage on smoking behavior, and (c) its ultimate impact on cigarette and tobacco cessation.

The important challenge is that these issues be examined soon before novel smokeless tobacco products, and PREPs in general, reach wide popularity. As a pilot study, the current investigation was not designed as a complete test of smokeless tobacco and its impact on smoking. As such, there are notable limitations within. In addition to the limited sample size, the lack of placebo control (there is no known placebo for Ariva/Stonewall), and a fairly short study period, limitations include a lack of rigorous biological verification of tobacco exposure. Our study collected CO, which (unlike cotinine, nicotine, anabasine, and anatabine) is the only biomarker of tobacco exposure that is sensitive to smokeless versus smoked tobacco (thiocyanate is another such biomarker but is often influenced by diet; Sherer, 2006).

However, CO is sensitive to only recent smoking behavior (Shields, 2002), and it is unclear how continuous assessment of tobacco exposure among smokers who concurrently use smokeless and smoked tobacco could be done effectively. Another limitation herein is that we assessed motivation to quit cigarette smoking but not motivation to quit all tobacco products. Although readiness to quit smoking increased among users of Ariva/Stonewall, the clinical interpretation of this increase would likely vary if these same individuals intended to quit/continue smokeless tobacco use. These limitations aside, we believe that this is only the third study (Mendoza-Baumgart et al., 2007; Tonnesen et al., 2008) to test directly (i.e.

, through randomized methods) the impact of smokeless tobacco among smokers, only the second (Tonnesen et al.) to report on prospective changes in smoking behavior and cessation, and the first to do so among smokers unmotivated to quit. In sum, results from the current study suggest no deleterious effect on smoking and quitting behavior among smokers who do not wish to quit but who use smokeless Entinostat tobacco. Smokeless tobacco could potentially serve as a method for cessation induction among unmotivated smokers.