Project summary. Electronic nicotine delivery systems (ENDS) heat and vaporize a nicotine-containing liquid
to produce an aerosol that can deliver nicotine to the blood and the brain. ENDS are considered tobacco products
in the US and are under the regulatory authority of the Food and Drug Administration. ENDS use has increased
rapidly in the last decade, especially among youth: over 20% of US high school students are current ENDS
users, and there is evidence of nicotine dependence in this population. Federal legislation has been proposed
that would restrict ENDS liquid nicotine concentration to make ENDS “significantly less addictive and appealing
to youth.” However, these and other efforts to curb addiction by limiting nicotine liquid concentration are unlikely
to succeed because nicotine emissions from ENDS depend on multiple variables. For example, where nicotine
concentration is limited, users can turn to a higher power ENDS device to attain more nicotine. To achieve the
intended public health aims, regulations targeting addiction must focus on nicotine delivery, not nicotine
concentration. While nicotine delivery cannot be regulated directly, the rate at which an ENDS emits nicotine,
the “nicotine flux” can be regulated and, importantly, predicted from first-principles based on knowledge of a few
device design and operating variables. However, to date there is no empirical evidence demonstrating the
relationship between flux and delivery, nor between flux and the physiological and subjective effects that support
nicotine dependence. Closing this gap is essential for providing an effective, first-principles framework for
regulating ENDS. In Aim1, we will examine the relationship between nicotine flux, nicotine form, and the rate
and dose of nicotine delivery. In the clinical lab at Yale University, participants will puff on ENDS devices under
conditions that differ by flux and form, while arterial blood is sampled in high time resolution. The outcome will
indicate the degree to which nicotine flux and form determine the speed and dose of ENDS nicotine delivery,
and thus, abuse liability. In Aim2, we will assess the relationship between nicotine flux, form, and subjective
effects. At the American University of Beirut, participants will use ENDS devices with varying nicotine fluxes and
forms. Dependency measures, such as urge to smoke, craving, and abstinence, will be assessed. The outcome
will indicate the degree to which nicotine flux/form influence subjective effects related to dependency, puffing
intensity, and exposure to toxicants. In summary, this project will provide the empirical evidence needed for
public health agencies to use nicotine flux as an encompassing and convenient construct to regulate nicotine
delivery from ENDS.
