This study is designed to examine how the nicotine content of cigarettes and the nicotine concentration and flavors in e-liquids influence responses to and use of these products in adolescent smokers. Participants will complete a total of six sessions (an in-person screening/baseline session and five lab sessions.

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 15-20
2. Adolescents who report current daily or near 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 tobacco products (other than ENDS or roll-your-own tobacco) > 15 days in the past 30 days.
4. 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)
5. Self-reported illicit use of any drug except marijuana > 10 days in the past 30 days
6. Binge drinking alcohol (>10 days in the past 30 days, >4/5 drinks in a 2-hour period (female/male))
7. Pregnant or breastfeeding
8. CO reading > 80 ppm
9. 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.
10. Indicating Yes on Questions 4-6 on the MINI with a suicide attempt in the past 2 years (if within the past 2-10 years, LMP approval required).
11. Having participated in another research study during the past year in which they were switched to reduced nicotine cigarettes for longer than one week.

Intend to share findings from this research through publications and presentations. Institutions and individuals wishing to access any resources or data must contact the Principal Investigator (Hatsukami). Data will be available in two formats. One will be a summary of the data, with graphs and tables, posted as pdf files and as raw individual-level data for analysis. Data generated by this grant will be made to outside investigators, according to NIH Guidance. When data are shared, there will be no limits placed on how the data will be used. Users will agree, however, that the recipient must not transfer the data to other users and that the data are only to be used for research purposes. A record of transfer of data and a copy of the dataset that was distributed will be kept by Brown University.

Data will not be available until primary and secondary papers are accepted for publication.

Persons requesting data must do so in writing, identifying their affiliation and how the data will be used. Upon review, access will be determined.

Participants who were randomized at Lab Session 1

Adverse events were assessed at each of 5 laboratory sessions, which occurred 2-7 days apart. The shortest assessment time (i.e., from the first to the last session) was 12 days; the longest was 40 days. At the 30-day follow-up call, any adverse events that remained open (i.e., were still ongoing) were assessed; no new adverse events were assessed for at the 30-day follow-up call.

SAEs were defined per clinicaltrials.gov definitions. Other (Not Including Serious) Adverse Events were defined as AEs classified as 'severe' by the medical monitor.

Participants will be blind to the nicotine content of their assigned study cigarette and the nicotine dose of the e-liquid in the study vaping device. Investigators, research staff, and biostatisticians will also be blind to the conditions. E-liquid flavors will not be blinded.