This study shows that there are significant differences in the nicotine pharmacokinetics and in the subjective effects of various forms of smokeless nicotine products. The use of Copenhagen resulted in the greatest exposure of nicotine and was associated with the lowest levels of craving and the highest scores on many aspects of product effects and liking. Medicinal use of nicotine resulted in greater exposure to nicotine and higher Cmax than the use of either Ariva or Revel. Medicinal nicotine was equivalent to the PREPs studied with respect to drug effects and liking measures, and nicotine‐withdrawal symptoms, and resulted in lower craving scores than those observed with one of the other products studied (ie, Revel).
Considering that Copenhagen was the regular brand for all the subjects in this study, it is not surprising that use of Copenhagen was associated with the lowest levels of craving and the highest ratings of many measures of product effects and liking. Additionally, use of Copenhagen resulted in far higher concentrations of nicotine than the use of any of the other products, further explaining Copenhagen's subjective effects. The relative rapid delivery of substantial amounts of nicotine during use of Copenhagen is consistent with that reported previously.12,21
The peak concentrations of nicotine obtained from the nicotine lozenge were similarly comparable with previous reports.22
Interestingly, two of the tobacco products studied (ie, Ariva and Revel) did not result in any sustained increase in plasma nicotine concentrations, and all three of the reduced exposure products (Ariva, Revel and Stonewall) resulted in lower maximal nicotine concentrations than the nicotine lozenge. This is consistent with our results indicating that the subjective effects from use of medicinal nicotine were either equivalent to or in the case of craving, superior to the effects reported from using the new tobacco products.
The use of nicotine replacement therapy as an aid to smokeless tobacco cessation has not been studied extensively; however, the available data suggest that at best it results in small increases in smokeless tobacco cessation rates.23
The PREPs studied do not seem to have either pharmacokinetic characteristics or subjective effects that would suggest they would be more effective than medicinal nicotine in increasing quit rates from older smokeless tobacco products (eg, moist snuff). However, the potential of PREPs to cause diseases associated with smoking or smokeless tobacco use (eg, cancer and cardiovascular disease) is largely unknown. An in vitro study assessing the amount of tobacco‐specific nitrosamines in the new tobacco products has found that although levels found in these three PREPs were lower than that found in Copenhagen, there was a wide variability between products (ie, levels in Revel were higher than in either Ariva or Stonewall) and all products had higher levels than the trace amounts found in medicinal nicotine.7
Although the dosages studied are those recommended on the packaging of the products evaluated, actual use may differ substantially and probably depends on multiple factors such as cost, packaging and marketing. Overall daily exposure to nicotine will depend on the pharmacokinetic properties of these products and on the frequency and pattern of use throughout the day. Additionally, unlike medicinal nicotine, which in the US is subject to regulation by the Food and Drug Administration, tobacco products (including PREPs) do not undergo review by regulatory agencies. Marketing for the reduced exposure and spitless products has suggested that these products are safer than cigarettes and may either completely substitute for smoking or be good alternatives to smoking in areas where smoking bans preclude cigarette use.24
Since the number of cigarette smokers in the US is currently much higher than the number of smokeless tobacco users, these advertising strategies have been aimed largely at cigarette smokers rather than at users of traditional smokeless tobacco products.25
Medicinal nicotine, in the US, is approved only as an aid for complete cessation and not as an aid for harm‐reduction strategies such as long‐term substitution of tobacco or for acute use where smoking restrictions are imposed. Manufacturers of medicinal nicotine therefore cannot similarly advertise these agents. This disparate regulatory environment may therefore lead to differences in the marketing of these products and therefore to differences in the acceptance and use of these products.
Our study does not deal with the subjective effects of these products in cigarette users, but the pharmacokinetic characteristics of the products would make it doubtful that these products would provide greater physical satisfaction to smokers than would medicinal nicotine. Furthermore, it is unlikely that products such as Ariva or Revel would totally substitute for smoking because of the low levels of nicotine delivery. Given the unknown risks of these products, medicinal nicotine would be a more appropriate alternative for smokers unable to smoke because of smoking restrictions but wanting to reduce craving and withdrawal symptoms.
In conclusion, our study found that among regular users of smokeless tobacco, nicotine concentrations during use of Copenhagen were substantially higher than during use of any of the three new PREPs or during use of medicinal nicotine. Consequently, use of Copenhagen was associated with the lowest craving scores and the highest ratings on drug effects and liking characteristics. Among the other four products studied, medicinal nicotine resulted in higher nicotine concentrations and was equivalent to or superior to the other agents in reducing craving. Since the health risks of the new smokeless tobacco products are largely unknown, our study suggests that smokeless tobacco users or smokers seeing a safer product should be encouraged to use medicinal nicotine rather than any of the other products assessed in this study.
What this paper adds
- New smokeless tobacco products, often marketed as potential reduced exposure products that are safer or more convenient to use than cigarettes, are being introduced into the marketplace. There is at this time, however, little information regarding the nicotine pharmacokinetics of these products or their effects on nicotine craving, nicotine withdrawal and other subjective measures of product effects or liking.
- This study examined these measures for three of the new smokeless tobacco products (Ariva, Revel and Stonewall) and found that compared with medicinal nicotine (Commit lozenge), use of these products results in lower nicotine concentrations and in either equivalent or higher ratings on subjective measures. Since the health effects of these newer products are largely unknown, smokers or smokeless tobacco users wishing to switch to a lower‐risk product should be encouraged to use medicinal nicotine.