Nicotine Absorption Profile Among Regular Users of a Pod-Based Electronic Nicotine Delivery System

This case series characterizes nicotine absorption among adults who regularly use a pod-based electronic nicotine delivery system.


Introduction
JUUL is a popular electronic nicotine delivery system (ENDS) 1 that contains a liquid with a high nicotine concentration (59 mg/mL). While there are concerns about the rapid increase in use of this potentially addictive product, 2 there are no independent published data, to our knowledge, on its blood nicotine absorption profile. This case series aimed to characterize nicotine absorption among regular adult users of this product and to evaluate subjective effects associated with use.

Methods
Current adult users of pod-based ENDS (n = 6), recruited via community flyers from November 2018 to May 2019, abstained from cigarette smoking for 4 days (carbon monoxide concentration verified as <8 ppm) and from any nicotine-containing product for at least 14 hours prior to attending a 1-day laboratory visit. Users completed baseline demographic and device questionnaires, including the Penn State Electronic Cigarette Dependence Index (PSECDI). 3 Users were then instructed to puff on their own pod-based ENDS (nicotine concentration 59 mg/mL) every 20 seconds for 10 minutes.
Blood was collected via catheter at baseline, while vaping (1, 2, 4, 6, 8, and 10 minutes), and after vaping (2 and 5 minutes after the last puff). Users rated withdrawal symptoms and subjective effects (scale of 0-100, with 100 indicating greatest effect) before and after vaping. Serum samples were analyzed for nicotine, cotinine, and 3-hydroxycotinine concentrations by liquid chromatography with tandem mass spectrometry. 4 Outcomes included the maximal concentration, time to maximal concentration, and nicotine boost (maximal concentration minus the baseline nicotine level). Paired t tests were used to evaluate within-participants differences in subjective measures from before vaping to after vaping. Statistical significance was set at 2-sided P < .05. Statistical analysis was performed using SAS version 9.4 (SAS Institute Inc).
This study was approved by the Penn State College of Medicine institutional review board, and all participants provided written informed consent. Data are reported using the reporting guideline for case series.

Discussion
Among experienced users who took 30 puffs in 10 minutes, the pod-based ENDS delivered a mean nicotine boost of 28.6 ng/mL in a mean of 8.7 minutes. This is higher and faster than the mean nicotine boost obtained from "cigalike" ENDS devices (puff activated and similar size and shape as a traditional tobacco cigarette; 1.8 ng/mL, 10 minutes) and advanced ENDS devices (button-activated with larger battery; 10.8 ng/mL, 12.1 minutes) using the same puffing schedule. 4 These users also self-reported higher nicotine dependence on the PSECDI, compared with 3609 experienced longterm users of other ENDS devices (mean PSECDI score, 8.1). 3 This study is the first, to our knowledge, to show that JUUL delivers a higher and faster boost in blood nicotine than has been reported for most other ENDS devices. [4][5][6] Limitations are the small   sample size and that ENDS users may not typically take 30 puffs in 10 minutes. However, its use produced a mean (SD) nicotine boost of 12.9 (9.8) ng/mL after only 12 puffs in 4 minutes, a rate suggestive of pulmonary absorption. Compared with studies reporting the nicotine boost obtained after smoking 1 cigarette, this product's nicotine delivery was similar. 4,6 The nicotine delivery capabilities of this ENDS device may contribute to its addictiveness as well as its ability to compete with cigarettes for market share.