An Open-Label, Randomised, Controlled, Crossover Study to Assess Nicotine Pharmacokinetics and Subjective Effects of the JUUL System with Three Nicotine Concentrations Relative to Combustible Cigarettes in Adult Smokers.

Abstract

INTRODUCTION\nThis randomised, openlabel, crossover clinical study evaluated nicotine pharmacokinetics (PK) and subjective effects of the JUUL System (JS; Juul Labs, Inc.) with three nicotine concentrations compared to usual brand (UB) cigarettes in 24 adult smokers.\n\n\nMETHODS\nAt five study visits subjects used either the JS in 59\xa0mg/mL, JS 18\xa0mg/mL (two visits) and JS 9\xa0mg/mL (all tobacco-flavoured) or smoked their UB cigarette first during controlled puffing sequence (CPS) and then ad libitum (5 minutes) use sessions. Blood samples were taken at specified timepoints for 60 minutes in each session. The modified Product Evaluation Scale assessed subjective effects 30-minutes post-use in the CPS session.\n\n\nRESULTS\nMaximum plasma nicotine concentration (CmaxBL), total nicotine exposure (AUC060BL) 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\xa0mg/mL compared to 18\xa0mg/mL and 9\xa0mg/mL. Subjective measures of cigarette craving relief and Enough Nicotine for JS 59\xa0mg/mL did not differ significantly from UB cigarettes, but JS 18\xa0mg/mL and 9\xa0mg/mL were rated significantly lower than JS 59\xa0mg/mL and UB cigarettes.\n\n\nCONCLUSIONS\nNicotine 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\xa0mg/mL to successfully transition away from cigarettes.\n\n\nIMPLICATIONS\nIt has been suggested that 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 compared to combustible cigarettes. We show that nicotine delivery from JS ENDS was nicotine concentration dependent, with higher nicotine concentrations giving rise to higher nicotine exposure. We suggest that heavier and more dependent smokers may require ENDS with nicotine concentrations greater than 20\xa0mg/mL in order to successfully transition away from cigarettes.