1. Potential Reduced Exposure Products (PREPs) for Tobacco Users: What Are They and What Do They Do ? Thomas Eissenberg, Ph.D. Department of Psychology and Institute for Drug and Alcohol Studies VCU Supported by NIH DA11082, DA06052, DA07027, RWJF’s Tobacco Etiology Research Network, VCU’s IDAS and Dept. of Pharm/Tox, VCU’s NCI-supported Massey Cancer Center

2. Topics to cover. What PREPs are currently available for tobacco users? What do we know that they do? What don’t we know that they do?

3. What PREPs are currently available? Cigarette-like PREPs for smokers (five). Oral PREPs for smokers (three). Oral PREPs for smokeless tobacco users (at least three).

4. Five cigarette-like PREPs for smokers. 1.RJR’s Eclipse ® – reduces carcinogenic compounds?

5. Five cigarette-like PREPs for smokers. 2.PM’s Accord ® – reduces secondhand smoke?

6. Five cigarette-like PREPs for smokers. 3.B&W’s Advance™ – reduces nitrosamine exposure?

7. Cigarette-like PREPs for smokers: 5 and 6 of 6. 4.Vector’s Omni™ – reduces PAHs, nitrosamines, catechols? 5.Vector’s Quest™ – reduces nicotine exposure?

8. Oral PREPs for smokers. 1.Ariva™ – Compressed powdered tobacco (“When you can’t smoke”). 2.Exalt™ – Small tobacco packet (“No smoking. No problem”). 3.Revel™ – Small tobacco packet (“Anytime. Anywhere.”).

9. Oral PREPs for smokeless tobacco users. Star’s Stonewall™ – reduces nitrosamine exposure? Small label products (“Bacc-off”) – reduces nicotine exposure? Swedish “snus” products – reduces carcinogen exposure? “Christmas is just around the corner and most of us dream of a white Christmas. We are planning to do our part in contributing to this. We are launching a totally new snus brand: Skruf, packed in an elegant white can...a really tasty snus with a pure tobacco flavor. A larger proportion of tobacco leaves are used than in traditional snus, making the Skruf stronger on nicotine.” Reasons to enjoy Bacc-off 1. Quit all tobacco 2. Cut down on tobacco use. 3. To reduce the nicotine use.

10. What do we know that these PREPs do? Do they reduce users’ toxin exposure? Do they decrease tobacco-related death and disease in today’s tobacco users? Do they increase the likelihood of tobacco use initiation? Do they decrease the prevalence of tobacco use cessation?

11. * 0 4 8 12 16 20 24 Plasma nicotine (ng/ml) * * Eclipse ® Own Accord ® What we know about Eclipse ® and Accord ®. Data from Breland et al., 2002a 90 Post 2.5-hour session Pre 2.5-hour session 0 10 20 30 40 50 * * * Expired air CO (ppm)   Own Eclipse ® Accord ® Eclipse ® 0 15 30 45 60 75 Withdrawal Score Own * * *  Accord ®  

12. What we know about Advance™ -- I pre 2.5-hour session post 2.5-hour session 0 10 20 30 40 50 Expired air CO (ppm) Own * * Advance™  0 5 10 15 20 25 30 Plasma nicotine (ng/ml) * Own * Advance™  Data from Breland et al., 2002b

13. What we know about Advance™ -- II 0 100 200 300 400 500 600 700 800 NNAL (pg/ml) 12345 Day No Smoking Own Brand Advance TM     Data from Breland et al., 2003

14. Other PREPs. Cigarette-like PREPs for smokers: - Omni™ – Delivers about 20% less NNK and 5% pyrene than normally marketed brands (Hatsukami et al., submitted) - Quest™ – Delivers less nicotine. Oral PREPs for smokers: no data available. May represent exposure increase. Oral PREPs for SLT users: - Stonewall™ – No data available. - Small label products – Some deliver no measurable nicotine. - Swedish “snus” products – Delivers about 50% NNK than U.S. brands (Hatsukami et al., submitted).

15. What do we know that these PREPs do? Some PREPs for smokers reduce toxin exposure: - Eclipse ® reduces exposure to nicotine (but increases CO exposure). - Accord ® reduces exposure to CO and nicotine (but does not suppress tobacco withdrawal). - Advance™ reduces exposure to nitrosamine (NNK) and CO but may increase nicotine exposure. - Omni™ reduces exposure to nitrosamine (NNK) and pyrene. - Quest™ reduces nicotine exposure. Snus may reduce NNK exposure. Of course, NRT products eliminate nitrosamine and CO exposure.

16. What do we not know that these PREPs do? Do oral PREPs for smokers increase toxin exposure? Does any PREP actually decrease tobacco-related death and disease in today’s tobacco users? Do PREPs increase the likelihood of tobacco use initiation? Do PREPs decrease the prevalence of tobacco use cessation?

17. Much work needed to find out what PREPs do. Restrict marketing until rigorous, objective data can be used to make reasonable hypotheses regarding harm reduction. Implement post-marketing surveillance to test hypotheses. Develop methods to determine if any PREP-associated reduction in health risk will be offset by increased initiation/decreased cessation. Consider NRT as a harm reduction strategy.

18. Why PREP evaluation is needed now. Source: Dr. Ken Warner.