REN-Project 2 Cigarette and E-cigarette Nicotine Content and E-liquid Flavors

Inclusion Criteria:

1. Age 18+

2. Daily smokers who smoke an average of at least five and 50 or fewer cigarettes per day
for the last month.

3. Must have used a vaping device on 2 or more separate occasions before participating in
the trial

4. Expired breath carbon monoxide (CO) level to assess recent smoking. Carbon monoxide
level must be > 10 ppm to confirm regular daily smoking. If CO is <10 ppm, NicAlert
strips will be used to assess urinary cotinine quantity to confirm smoking status. A
result of 2,000 ng/mL is needed to verify regular daily smoking.

5. Fulfills need for participants in the required strata (age range)

Exclusion Criteria:

1. Unwilling to use research cigarettes or a vaping device as part of the trial

2. Currently trying to quit or intending to quit smoking in the next 60 days

3. Currently seeking treatment for smoking cessation

4. A quit attempt in the past 30 days resulting in greater than 3 days of abstinence

5. Using tobacco products, including nicotine replacement therapies or other
pharmacotherapies (other than cigarettes, vaping devices or roll-your-own tobacco)
more than 9 days in the past 30 days

6. Unwilling to smoke machine manufactured cigarettes as part of the trial

7. Use of vaping devices > 15 days of the last 30

8. Conditions in which participation is likely to pose a significant threat to health or
for which the condition could interfere with the ability of the participant to fully
participate

9. Significant unstable medical conditions (any significant change in a serious medical
condition occurring during the past 3 months including cardiovascular disease, COPD,
and cancer, as determined by the licensed medical monitor)

10. Significant unstable psychiatric conditions (any significant change in psychiatric
symptoms during the past 3 months as determined by the licensed medical monitor)

11. Schizophrenia and schizoaffective disorder

12. Positive toxicology screen for any of the following drugs: cocaine, opiates,
methadone, benzodiazepines, barbiturates, amphetamines, methamphetamines, and PCP.
Positive test for marijuana only allowed. Failing temperature strip for the sample or
unable to provide enough urine sample for the drug screen.

a. Participants with valid prescriptions for opiates, benzodiazepines, barbiturates,
amphetamines or methadone (clinic letter) will not be excluded.

13. Self-reported illicit use of any drug including marijuana ≥ 10 days in the past month

14. Breath alcohol level > 0.01 (g/dL), as measured by a breath sample.

15. Binge drinking alcohol (more than 9 days in the past 30 days, 4/5 drinks in a 2-hour
period (female/male))

16. Pregnant, trying to become pregnant or breastfeeding

17. Failure to agree to use adequate protection to avoid becoming pregnant during the
study

18. Currently taking any one of the following medications:

1. Phenytoin [Brand Name: Dilantin]

2. Carbamazepine [Brand Name: Tegretol, Carbatrol, Equetro, Epitol]

3. Oxcarbazepine [Brand Name: Trileptal]

4. Primidone [Brand Name: Mysoline]

5. Phenobarbital

6. Bendamustine [Brand Name: Treanda]

7. Clopidogrel [Brand Name: Plavix]

8. Clozapine [Brand Name: Clozaril, FazaClo]

9. Erlotinib [Brand Name: Tarceva]

10. Flecainide [Brand Name: Tambocor]

11. Fluvoxamine [Brand Name: Luvox]

12. Irinotecan [Brand Name: Camptosar]

13. Olanzapine [Brand Name: Zyprexa]

14. Tacrine [Brand Name: Cognex]

15. Theophylline [Brand Name: Theo Dur]

19. CO reading >80 ppm

20. Systolic BP greater than or equal to 160 mm/Hg

a. Participants failing for blood pressure will be allowed to re-screen once.

21. Diastolic BP greater than or equal to 100 mm/Hg

a. Participants failing for blood pressure will be allowed to re-screen once.

22. Systolic BP below 90 mm/Hg

a. Participants failing for blood pressure will be allowed to re-screen once.

23. Diastolic BP below 50 mm/Hg

a. Participants failing for blood pressure will be allowed to re-screen once.

24. Heart rate greater than or equal to 105 bpm

a. Participants failing for heart rate will be allowed to re-screen once.

25. Heart rate lower than 45 bpm

a. Participants failing for heart rate will be allowed to re-screen once.

26. Indicating any suicidal ideation in the past month or suicide attempts in the past 5
years (if within the past 6-10 years, LMM approval required).

27. Inability to independently read and comprehend the consent form and other written
study materials and measures.

28. Having participated in a research study during the past three months in which the
participant:

1. Smoked a cigarette that was not his/her usual brand cigarette for more than one
day

2. Used any tobacco products beyond normal use for more than one day

3. Used any nicotine replacement products or smoking cessation medications for more
than one day

29. Having participated in prior studies involving reduced nicotine cigarettes in the past
three years.

30. Household member enrolled in the study concurrently

31. Self-reported allergies to propylene glycol and/or vegetable glycerin.

32. Previous adverse reactions when using vaping devices.