The purpose of this acute study was to describe clinical laboratory methods that could be used to understand ECs better by examining users’ toxicant exposure, cardiovascular response, and subjective reports. Results of this study demonstrate the usefulness of the clinical model and suggest that, unlike puffing from a tobacco cigarette, two 10-puff bouts with the two ECs described here exposes users to no measurable nicotine or CO and does not increase heart rate. Despite the failure to deliver nicotine, acute use of the two products tested in this study produced some tobacco abstinence symptom suppression and increased subjective ratings of acceptability. Relative to the effects produced by an own brand tobacco cigarette, these subjective effects of ECs were modest.
With regard to nicotine exposure, the observation that 20 puffs from “Hydro” EC (16 mg cartridge) and “NPRO” EC (18 mg cartridges) did not increase plasma nicotine concentration significantly is entirely consistent with our preliminary report regarding these products (21
). The plasma nicotine results are also consistent with the heart rate data reported here. That is, heart rate increases are observed when nicotine is administered via pharmaceutical products (e.g., 33
) or tobacco products (e.g., 31
) and we observed increased heart rate when participants in this study smoked their own brand of cigarette (that also delivered nicotine). However, no heart rate increases were observed in either EC condition (where no significant increases in plasma nicotine were observed). Finally, the mean peak change from baseline in plasma nicotine concentration observed for “NPRO” EC (1.4 ng/ml) and “Hydro” EC (0.5 ng/ml) during the first product administration were similar in magnitude to the maximum nicotine concentration reported for a third EC brand with a 16 mg cartridge (1.3 ng/ml; 20). The consistency of results across participants, measures, and laboratories highlights the reliability of the clinical methods reported here (see also 26
), while also calling into question the ability of the three different ECs that have been tested to date to approximate the nicotine delivery of a tobacco cigarette under acute conditions.
In spite of delivering no measureable nicotine, both ECs tested in this study reduced ratings of “craving a cigarette” and “urge to smoke” and increased subjective ratings of product acceptability (e.g. “satisfying”, “taste good”, “pleasant”). These results are consistent with anecdotal reports from long-term EC users and support the notion that ECs may provide an alternative – perhaps a substitute – to cigarette smoking in some cases (11
). Interestingly, de-nicotinized cigarettes have also been shown to suppress tobacco abstinence symptoms for as long as 96 hours (40
). However, under the acute conditions reported here, the two ECs did not suppress nicotine/tobacco abstinence symptoms fully, relative to own brand smoking. Other PREPs that failed to suppress abstinence symptoms fully have been shown to supplement rather than substitute for cigarette smoking (e.g., 9
). Further controlled evaluation is needed to determine the extent to which the effects reported here are sufficient for ECs to substitute for tobacco cigarettes, and in what proportion of smokers and under what conditions this substitution effect might occur.
Importantly, neither of the ECs tested in this study were associated with any measurable CO exposure. Long-term CO exposure has been linked to cardiovascular disease caused by tobacco cigarette smoking (36
). In part for this reason, substituting non-combustible tobacco or nicotine products for cigarettes has been suggested as a potentially effective strategy for reducing the harm of tobacco smoking (37
). Following this same logic, and taking into account the trace levels of tobacco specific nitrosamines found in some EC products (13
), ECs may also warrant careful empirical examination by those interested in harm reduction for smokers. Clinical laboratory methods have an important role to play in this empirical examination, and can reveal carcinogen exposure and abstinence symptoms suppression over several days’ PREP use (e.g., 22
). These methods will likely be extremely important to any future regulation of ECs either as tobacco products or drug delivery devices in the U.S. (i.e., by the Food and Drug Administration) and elsewhere.
Methodological considerations of the current study include the brief EC exposure period, rigorous control over some aspects of smoking behavior, use of two brands of EC with similar cartridge nicotine content, and inclusion of EC-naïve participants who may be representative of cigarette smokers sampling an EC for the first time, but not of a more experienced EC user population. Results of some outcome measures might be influenced by longer-term use, different puffing profiles, other EC models/cartridge strengths, and/or the user’s previous experience with ECs. In future studies, control conditions other than own brand and sham smoking might be of interest. Indeed, a recently published study compared the subjective and physiological effects of another brand of EC, the Ruyan® EC, to that of a pharmaceutical nicotine inhalator and found that the two products were associated with similar low levels of nicotine exposure, incomplete withdrawal suppression, and moderate acceptability (20
).. In addition, behavioral studies that assess the reinforcing/rewarding properties of ECs could reveal the extent to which ECs might be used or abused. (41
). Finally, the adverse event profile associated with long-term use of ECs is uncertain, and must be explored empirically. Many of these methodological issues and research questions can be addressed parametrically and conveniently in the clinical laboratory, highlighting the strength of these efficient and reliable evaluation methods (see also 26
In sum, this study revealed that two EC brands do not expose EC-naïve users to nicotine or carbon monoxide under the acute testing procedures described here, but do produce some tobacco abstinence symptom suppression and positive ratings of product acceptability. While these results are necessarily a function of the products tested and procedures used, they suggest that EC-naïve individuals may require substantial motivation if they are to learn whatever product/procedure combination maximizes these outcomes for them. Future clinical laboratory evaluation can build on these methods and results to establish the extent to which ECs might be expected to substitute for tobacco cigarettes, and help to identify under what conditions this substitution might occur. Parallel studies addressing the abuse liability and long-term adverse event profile of ECs are also required to ensure safety and appropriate labeling and marketing of these products.