This study found that enrolling smokers in a cessation study utilizing newer smokeless tobacco products is feasible. The proportion of subject dropping out in those assigned to one of two smokeless tobacco products (i.e. Camel Snus, Taboka) was similar to the proportion assigned to medicinal nicotine and the overall drop-out rate during the treatment period was comparable to other smoking cessation studies (25
). Although many of those who initially responded to advertisements did not subsequently enroll in the study, many of the reasons for not enrolling were not reasons that suggest a resistance to using the study products (e.g. some could not be reached by telephone, others did not meet inclusion/exclusion criteria). Overall, this study therefore found smokers were willing to enroll and complete a cessation study which used the newer tobacco products and did not find that smokeless tobacco was superior to nicotine replacement in decreasing craving or withdrawal symptoms; however nicotine replacement use resulted in larger decreases in total NNAL than Camel Snus.
Differences in how the three products were used may be related to the amount of nicotine in each of the products. Subjects used significantly fewer doses of Taboka than either Camel Snus or the nicotine replacement product. A recent study found that Taboka had 0.844–1.26 mg free (unprotonated) nicotine/gram dry weight and 19.9–21.1 mg total nicotine/gram dry weight, whereas Camel Snus had 6.09–9.16 mg free nicotine/gram dry weight and 23.7–28.2 mg total nicotine/gram dry weight (15
). Products with similar amount of nicotine as Taboka (e.g. Revel) have been found to result in lower plasma nicotine concentrations than the nicotine lozenge (5
). Therefore, the nicotine concentrations obtained from Taboka may not have been sufficient to maintain product use. Very low nicotine cigarettes, or nicotine free cigarettes, have shown promise as potential aids for cessation but it is not clear that low nicotine smokeless products would be equally effective (28
). Unlike the extra low nicotine or nicotine free cigarettes, low nicotine smokeless products are likely not as effective at substituting for the sensory and behavioral aspects of smoking. This is consistent with the finding that during the last week of treatment those receiving Taboka smoked significantly more of their usual brand cigarettes than those assigned to either of the other two treatments. Our study therefore suggests that for smokeless products to be effective at substituting for cigarettes, nicotine concentrations likely have to surpass a certain threshold. Quit rates for Camel Snus were comparable to those obtained with nicotine replacement therapy, therefore a properly powered study is needed to determine if use of smokeless tobacco products with higher nicotine content can be an effective path to smoking cessation, perhaps especially among smokers who are not interested in or previously were not successful with using approved pharmacotherapies.
This study addressed the issue of whether switching smokers to smokeless tobacco offers any advantages relative to switching to medicinal nicotine. In the various outcomes assessed (i.e. craving, withdrawal symptoms, toxicant concentrations), no clear advantages were found for smokeless tobacco over medicinal nicotine. Previous studies similarly found few differences in subjective measures after use of a single dose or repeated doses of some of the newer smokeless tobacco products vs. nicotine lozenge and have shown no significant increases in craving after switching from cigarettes to medicinal nicotine or other newer products (27
). However, studies assessing these measures are relatively small and may not be able to detect small differences between groups. In measures of toxicant exposure, switching to medicinal nicotine resulted in lower levels of NNAL than switching to one of the smokeless tobacco products. This is consistent with other studies demonstrating that many of the newer smokeless tobacco products, although having lower levels of toxicants than cigarette smoke, are not toxicant free (6
). The lack of significant differences among groups in total NNN exposure was perhaps due (at least in part) to endogenous NNN production (from nicotine) in those receiving medicinal nicotine (34
). Further research is needed to determine the extent to which this occurs. This study therefore suggests that for smokers interested in quitting, medicinal nicotine should be the first option recommended and barriers to medicinal nicotine use should be identified and removed if possible.
Several limitations are present in the current study. Smokeless tobacco products commercially available in the United States have been introduced, withdrawn or changed at a relatively rapid rate. As a result, one of the products tested in the current study (Taboka) is no longer commercially available and changes to the other product (Camel Snus) occurred during the time period that the study occurred. Nonetheless, the study provides important information regarding the feasibility of conducting studies with these products and information regarding toxicant exposure during their use. Lack of commercial availability of these products for most of the subjects during the follow-up period precludes evaluating if and how smokers introduced to these products would use them in a natural setting once these products were no longer provided by the study. An additional limitation is that in the measurement of toxicant exposure, it is not known how much of the exposure was contributed by the study products as compared to cigarettes that subjects were smoking during the study (i.e. since the amount of product used and the amount smoked differed significantly between groups). A strength of this approach, however is that it more closely resembles toxicant exposure when these smokers are given these products in the natural environment. Furthermore, when examining smokers who were verified to be abstinent, those assigned to Camel Snus continued to have higher toxicant exposure compared to those assigned to medicinal nicotine. It should be noted that the results of this study are limited in applicability only to smokers who are interested in quitting smoking and willing to use nicotine replacement therapy. It is not known how these products would compare in smokers not interested in cessation or smokers interested in cessation but not interested in using nicotine replacement therapy. Future studies are needed to address these issues.
In summary, this study demonstrated that smokers interested in quitting smoking were willing to enroll in and complete a study evaluating the newer smokeless tobacco products. Additionally, this study did not find that the “modified risk” smokeless tobacco products tested were superior to medicinal nicotine in decreasing subjective measures (i.e. craving, withdrawal) but resulted in greater exposure to one of the toxicants assessed. Further studies are needed to definitively determine if these products are effective at increasing cessation rates and to determine how smokeless tobacco products might be used in smokers not immediately interested in smoking cessation.