1. New Tobacco Products: Harm Reduction or Harm Induction? Herbert H. Severson Senior Research Scientist Oregon Research Institute Eugene, Oregon

2. Harm Reduction Definition Harm reduction refers to minimizing harms and decreasing total morbidity and mortality, without completely eliminating tobacco and nicotine use Institute of Medicine study, 2001

3. New Products Lower tobacco-specific nitrosamines Spitless In neat packets Different flavors Snus products produced by American Tobacco Companies

4. New Smokeless Products

5. Urgency for Research Increased advertising directed at smokers and influx of new products Controversy over the use of smokeless tobacco as a harm reduction agent Little data to determine the impact of these products and to support it’s use as a harm reduction agent

6. State of affairs Scientific consensus on lower risks to individual users of ST and at the same time Adamant dissension, sometimes bitter & personal, on whether ST can help to reduce population tobacco harm

7. What We Know - Point #1 Wide variability in tobacco-specific nitrosamines (TSNAs) in non- combustible oral products Considerable levels of carcinogenic tobacco-specific nitrosamines even in newer oral tobacco products

8. Tobacco-Specific Nitrosamines Across Products Productµg/g product (wet weight) NNNNNKNATNABTotal Copenhagen Snuff2.200.751.800.124.80 General Snus0.980.180.790.062.00 Camel Snus (frost)0.830.160.140.011.12 Taboka0.910.060.230.001.27 Revel0.620.030.320.020.99 Ariva0.020.040.120.010.19 Commit (lozenge, 2 mg nicotine) nd

9. What We Know - Point #2 Significant reductions in toxicant uptake can occur when tobacco users switch from products with higher TSNAs to products with lower TSNAs

10. Urinary Total NNAL in Smokeless Tobacco Users Who Switched to Snus or Nicotine Patch

11. What We Know - Point #3 Wide variability in levels of free nicotine in oral tobacco products Considerable amounts of free nicotine in some of the newer tobacco products that may sustain addiction

12. What We Know: Wide Variability in Nicotine Levels Across Products ProductpH Nicotine (mg/g dry weight) TotalFree Copenhagen Long Cut7.5326.77.14 Skoal Long Cut7.5125.66.03 Marlboro Snus Rich6.8025.2*1.42* Camel Snus Original7.4628.26.09 General Snus7.9516.77.69 *increased in the past year: 2008 values; total 17.8, free 1.08 I. Stepanov et al, Nicotine Tob. Res. 12: 1773 (2008)

13. What We Know Products with lower TSNAs are not benign Oral pathologies Pancreatic cancer Metabolic syndrome Fetal toxicity Cardiovascular disease?

14. Reasons for opposing use of ST for reducing population tobacco harm

15. “(a)... limited studies to show that the dual use of smokeless tobacco and cigarettes is not as harmful or more harmful than the single use of these products.” 1. “Main concern with marketing ST as cessation aid or substitute for cigarettes”

16. Sequential or Concurrent Dual Use? Sequential “dual” use (moving completely off cigarettes to ST) will very likely show some reduction in smoking-caused diseases—as a function of duration of smoking & daily dose of smoking As with dual use of NRT and cigarettes in smokers who do not want to quit smoking*, because nicotine intake is somewhat regulated, total intake of smoke toxins is unlikely to rise with dual use and will likely decrease * Fagerstrom, KO, Tejding R, Westin A, Lunell E. Aiding reduction of smoking with nicotine replacement medications: hope for the recalcitrant smoker? Tob Control. 1997 Winter;6(4):311-6.

17. “(b) Aggressive marketing of smokeless tobacco as less risky than cigarettes may not necessarily lead to reduced total tobacco use but increased use, especially newly initiated use.” 2. “Main concerns with marketing ST as cessation aid or substitute for cigarettes”

18. “(c) Oral smokeless tobacco products are not harmless....” lower standard for toxins [There is a need for a regulatory authority to set a] “lower standard for toxins and require disclosure over these products” [to be able to] “assess true harm from oral tobacco use.” New FDA Regulations may develop these standards “Main concerns with marketing ST as cessation aid or substitute for cigarettes”

19. “... (d) smokeless tobacco use may be a gateway to using cigarettes. Whereas few smokers switch to smokeless tobacco, a greater number of smokeless tobacco users switch to cigarettes, a more deadly product

20. “No Consensus on Gateway” In support for gateway Tomar SL. Is use of smokeless tobacco a risk factor for cigarette smoking? The U.S. experience. Nicotine and Tobacco Research, 2003;5(4):561-70. Severson, H.H., Forester, K.A., & Biglan, A. (2007). Use of smokeless tobacco is a risk factor for cigarette smoking. Nicotine & Tobacco Research 9(12); 1331-1337. In opposition to gateway O’Connor RJ, Flaherty BP, Edwards BQ, et al. Regular smokeless tobacco use is not a reliable predictor of smoking onset when psychosocial predictors are included in the model. Nicotine and Tobacco Research, 2003; 5(4), 535-44. Ramstrom LM, Foulds J Role of snus in initiation and cessation of tobacco smoking in Sweden. Tob Control. 2006 Jun;15(3):210-4.

21. Arguments For ST Use for Cigarette Harm Reduction Fewer negative health consequences associated with smokeless tobacco use compared to cigarettes Swedish snus experience

22. Arguments Against ST Use for Cigarette Harm Reduction ST use is harmful and less harmful products are available ST use leads to nicotine addiction ST may facilitate use of cigarettes Quitting ST is difficult

23. NIH State-of-the-Science Conference on Tobacco Use: Prevention, Cessation, and Control Data about the effectiveness of ST in facilitating smoking cessation and associated harm reduction are very limited. High-quality comparisons of ST to proven pharmacologic and behavioral cessation interventions are needed http://consensus.nih.gov/

24. What We Need to Learn Level of toxicants in these newer products Addictive potential of these products Consumer perception of these products Use of these products by consumers Health impact of these newer products Effectiveness of products as a smoking cessation aid What impact these products have on a population level (e.g., rate of initiation, maintenance, or precipitation of relapse)

25. Harm Reduction Study Hatsukami and Severson Randomized clinical trial comparing the efficacy of oral tobacco and pharmaceutical nicotine lozenges in smoking cessation Acceptability of ST products for cessation Assess the toxicity of tobacco exposure for participants in the RCT Funded by the National Cancer Institute

26. Product Preference of Six Oral Tobacco Products Provide data on preference of ST products Subjective rating of product Withdrawal symptoms during ST use Optional: Can choose to quit smoking using ST choice

27. ST Products Used in Study 1 Compared: Camel Snus – Mellow & Frost Marlboro Snus – Peppermint & Rich General Snus (Swedish) Stonewall – Java, Wintergreen, & Natural Ariva – Java & Wintergreen

28. ST Product Preference Study Design Week 9 Follow-Up Phone Call Week 5 Oral Tobacco Cessation Cessation Weeks 3 – 4 Smoking Cessation Using Product of Choice Sample Weeks 1 – 2 Three Oral Tobacco Products per Week Baseline Week 0 1 Week Data Collection Subject Orientation

29. Conclusion Whether smokeless tobacco is a viable treatment method for smoking cessation is unknown Developing more rapid and acceptable methods of nicotine delivery may be better alternative to using smokeless tobacco