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Effect of partial nicotine reduction on young e-cigarette users in the US: a cross-over clinical trial Tarana Ferdous* Tarana Ferdous

Background: The advent of salt-based, high-nicotine e-cigarettes has contributed to their
epidemic use among young people in the US, necessitating the need for policies to address the
addictiveness of these products. Therefore, using an experimental clinical design, this study
evaluates the effect of partial nicotine reduction (NR) on e-cigarette users’ puffing behaviors.

Methods: In this repeated-measure within-subject clinical cross-over study, 50 current high nicotine concentration e-cigarette users aged 21-35 attended two e-cigarette use sessions with the
same brand (JUUL/NJOY) of 3% (28-35 mg/ml) and 5% (58-59 mg/ml) nicotine concentration
in random order up to 60 minutes ad libitum, preceded by 12-hour nicotine abstinence. Puffing
topography was recorded during each session to measure smoking time, puff time, average puff
duration, average flow rate, average inter-puff interval, number of puffs, total inhaled volume,
average puff volume, and maximum puff volume. Blood samples were collected before and after
each session, and plasma nicotine levels were assessed retrospectively using gas
chromatography-mass spectrometry.

Results: The median topography parameters were significantly higher during the e-cigarette use
sessions with 3% nicotine concentration compared to the sessions with 5% nicotine
concentration (i.e., puffing time: 1.33 min vs. 1.21 min, p = 0.021; average puff duration: 2.57
sec vs. 2.44 sec, p=0.017; total inhaled volume: 1990 ml vs. 1490 ml, p = 0.045), indicating the
presence of compensatory puffing behavior for partial NR. The median nicotine boost observed
in the 5% nicotine condition (6.35 ng/ml) was significantly higher than in the 3% condition (4.10
ng/ml, p = 0.012).
Conclusion: Using a sensitive within-subject design, this study provides clear evidence of
compensatory puffing on e-cigarette use when partial NR is employed with the potential to add
to toxicants’ exposure.