Evaluating New Nicotine Standards for Cigarettes - Project 3

Adolescence is a critical developmental period for tobacco initiation and progression to
regular use and dependence. The Food and Drug Administration (FDA) has the authority to
establish standards for tobacco products for the protection of public health, including the
authority to mandate a reduction in the nicotine content of all cigarettes to minimally
addictive levels. Numerous studies have found that adult smokers who are switched to very low
nicotine content (VLNC) cigarettes experience reductions in smoking rates, nicotine intake,
nicotine dependence and abstinence-induced craving relative to those who use normal nicotine
content (NNC) cigarettes. However, studies of VLNC cigarettes in adolescent smokers are
limited and more information is needed to inform potential product standards. Furthermore,
use of electronic nicotine delivery systems (ENDS), e-cigarettes or vaping devices, has
increased dramatically in adolescents. Therefore, effects of VLNC cigarettes on smoking in
youth should be examined in the context of vaping device availability. This study is designed
to examine how the nicotine content of cigarettes and the nicotine concentration and flavors
in e-liquids influence responses to these products in adolescents.

Participants will complete an in-person baseline session in which eligibility criteria are
confirmed and background questionnaires are completed. Next, participants will complete five
in-person lab sessions in which NNC or VLNC cigarettes are available (based on random
assignment). During the first lab session, participants will test the assigned research
cigarettes when no alternative product is available. During each of the four remaining lab
sessions, smokers' responses to the assigned research cigarettes will be compared to their
responses to a vaping device with the following characteristics: 1) no nicotine, tobacco
flavor; 2) no nicotine, non-tobacco flavor; 3) moderate nicotine concentration, tobacco
flavor; or 4) moderate nicotine concentration, non-tobacco flavor. In each session, after
sampling and rating the subjective effects of the products available during that session,
participants will make a series of 10 choices. Choices will be for either 2 puffs of the
research cigarette, 2 puffs of the vaping device, or abstinence from puffing.

Inclusion Criteria:

1. Ages 15-19

2. Adolescents who report current daily cigarette smoking for at least 3 months

3. Must have used an electronic nicotine device on a minimum of two lifetime occasions.

4. Breath Carbon Monoxide (CO) levels > 5 ppm (if < 5 ppm, then cotinine assay via
NicAlert Strip = > 3)

5. Speak, comprehend, and read English well enough to complete study procedures

Exclusion Criteria:

1. Unwilling to use research cigarettes or ENDS as part of the study

2. Intention to quit smoking in the next 30 days

3. Using ENDS > 25 days in the past 30 days

4. Using tobacco products (other than ENDS or roll-your-own tobacco) > 10 days in the
past 30 days.

5. Any medical or psychiatric condition in which participation is likely to post a
significant threat to health or for which the condition could interfere with the
ability of the participant to fully participants (as determined by the LMP)

6. Self-reported illicit use of any drug except marijuana > 10 days in the past 30 days

7. Binge drinking alcohol (>10 days in the past 30 days, >4/5 drinks in a 2-hour period
(female/male))

8. Pregnant or breastfeeding

9. CO reading > 80 ppm

10. Systolic BP outside the range of 90-159, diastolic BP outside the range of 50-99, or
heart rate outside the range of 45-104. Participants failing for any of these criteria
will be allowed to re-screen once per criterion.

11. Indicating Yes on Questions 4-6 on the MINI with a suicide attempt in the past 5 years
(if within the past 6-10 years, LMP approval required).

12. Having participated in another research study during the past year in which they were
switched to reduced nicotine cigarettes for longer than one week.