Attention-deficit/hyperactivity disorder (ADHD)—a psychiatric condition involving persistent difficulty sustaining attention, hyperactivity, and impulsivity—was estimated to affect 7% of youth in a meta-analytic pooled estimate of studies published from 1981 to 2014,¹ and the rate may be increasing in some populations.² Because nongenetic environmental factors are associated with adolescent ADHD,³ increasing exposure to environmental risk factors may contribute to increasing ADHD rates in that population.

In 2016, 11% of US 10th grade students reported using (vaping) electronic cigarettes (e-cigarettes) in the past 30 days.¹ Prospective data demonstrate that youths who vape are more likely to initiate^2-6 and progress⁷ to more frequent and heavy smoking. However, the reasons for these associations remain largely unknown. Identifying factors that underlie the progression of smoking and vaping among adolescents is critical for understanding, estimating, and preventing adverse health consequences of e-cigarette use among youths.

This randomized, open-label, crossover clinical study evaluated nicotine pharmacokinetics (PK) and subjective effects of the JUUL System (JS; Juul Labs, Inc.) with three nicotine concentrations compared to the usual brand (UB) cigarettes in 24 adult smokers. At five study visits, subjects used either the JS in 59 mg/mL, JS 18 mg/mL (two visits), and JS 9 mg/mL (all tobacco-flavored) or smoked their UB cigarette first during a controlled puffing sequence (CPS) and then ad libitum (5 min) use sessions. Blood samples were taken at specified timepoints for 60 min in each session. The modified Product Evaluation Scale assessed subjective effects 30-min post-use in the CPS session. Maximum plasma nicotine concentration (C_max-BL), total nicotine exposure (AUC_0-60-BL), and rate of plasma nicotine rise were significantly lower for all JS products compared to subjects' UB cigarette in CPS and ad libitum use sessions. In both use sessions these PK parameters were significantly higher for JS 59 mg/mL compared to 18 and 9 mg/mL. Subjective measures of cigarette craving relief and “Enough Nicotine” for JS 59 mg/mL did not differ significantly from UB cigarettes, but JS 18 and 9 mg/mL were rated significantly lower than JS 59 mg/mL and UB cigarettes. Nicotine exposure and subjective relief were directly related to JS nicotine concentration: higher nicotine concentrations gave rise to significantly greater plasma nicotine levels and relief from craving. Heavier and more dependent smokers may require the greater nicotine delivery of JS 59 mg/mL to successfully transition away from cigarettes. It has been suggested that electronic nicotine delivery systems (ENDS) and other alternative nicotine delivery products that more closely mimic the nicotine pharmacokinetics (PK) of cigarettes may facilitate smokers transitioning away from cigarettes. We examined nicotine PK and subjective effects of JUUL System (JS) ENDS with three nicotine concentrations (59, 18 and 9 mg/mL) compared to combustible cigarettes. Nicotine delivery from JS ENDS was nicotine concentration dependent, with higher nicotine concentrations giving rise to higher nicotine exposure. These findings suggest that heavier and more dependent smokers may require ENDS with nicotine concentrations greater than 20 mg/mL to successfully transition away from cigarettes.