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Abstract
Background JUUL is an electronic cigarette that aerosolises a nicotine-containing liquid, while IQOS heats tobacco to produce an aerosol. Both are marketed to smokers, but their effects have seldom been examined in this population.
Methods Eighteen cigarette smokers (13 men) with no JUUL or IQOS experience completed a within-subject, laboratory study assessing nicotine delivery and subjective effects after controlled (10 puffs, ~30 s interpuff interval) and ad libitum (90 min) use of JUUL, IQOS or own-brand (OB) cigarettes.
Results JUUL increased mean plasma nicotine concentration significantly from 2.2 (SD=0.7) ng/mL to 9.8 (4.9) ng/mL after 10 puffs and to 11.5 (9.3) ng/mL after ad libitum use. IQOS increased mean plasma nicotine significantly from 2.1 (0.2) ng/mL to 12.7 (6.2) ng/mL after 10 puffs and to 11.3 (8.0) ng/mL after ad libitum use. OB increased mean plasma nicotine significantly from 2.1 (0.2) ng/mL to 20.4 (11.4) ng/mL after 10 puffs and to 21.0 (10.2) ng/mL after ad libitum use. Mean OB plasma nicotine concentration was significantly higher than JUUL and IQOS. OB increased expired carbon monoxide concentration, but IQOS and JUUL did not. ‘Craving a cigarette/nicotine’ and ‘Urges to smoke’ were reduced significantly for all products following the directed bout.
Conclusions Among smokers, JUUL and IQOS delivered less nicotine than cigarettes. Also, in this sample, IQOS and OB reduced abstinence symptoms more effectively than JUUL. Additional work with experienced JUUL and IQOS users is needed, as their nicotine delivery profiles and subjective experiences may differ.
- electronic nicotine delivery devices
- non-cigarette tobacco products
- addiction
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Introduction
Electronic cigarettes (ECIGs) are a heterogeneous class of tobacco products that use a battery-powered element to heat a liquid to produce a nicotine-containing aerosol. ‘Pod-mod’ ECIGs use replaceable reservoirs that combine the heating element with a liquid that often has a high concentration (50–60 mg/mL) of protonated nicotine (‘nicotine salt’). Relative to freebase nicotine aerosol, protonated nicotine may be less aversive to inhale.1 JUUL is a popular pod-mod device2 that contains 69 mg/mL nicotine liquid, 94% in the protonated form.3 While the tobacco industry has invested heavily in ECIGs,4 it also markets other types of electronic devices, such as heated tobacco products, that heat pressed tobacco (not a liquid) to produce an aerosol. One such product is ‘IQOS’ that heats pressed tobacco rods (‘HeatSticks’ or ‘HEETS’) to produce an aerosol that contains nicotine as well as some, but not all, of the non-nicotine toxicants in combustible cigarette smoke.5–7 The effects of JUUL or IQOS in cigarette smokers are largely unknown, so this study compares the biomarkers and subjective effects of JUUL and IQOS to own-brand (OB) combustible cigarettes in this population.
Method
The method for this VCU IRB-approved study was similar to that reported elsewhere.8 9 Briefly, community volunteers aged 18–55 who smoked >10 cigarettes daily and with expired air carbon monoxide (CO) >15 ppm at screening and who reported no JUUL or IQOS experience were recruited to complete three, ~4 hour, Latin-square ordered sessions that were each preceded by 12 hours of nicotine/tobacco abstinence (verified with CO <10 ppm and baseline plasma nicotine concentration <5.0 ng/mL8 10). Sessions differed by product used: JUUL (tobacco or mint flavour pod), IQOS (tobacco or menthol) or OB cigarette (OB; JUUL and IQOS flavours were matched to OB). Four sealed IQOS kits and ‘Amber Label’ and ‘Green Label’ ‘HeatSticks’ were purchased via eBay in September 2017. Five JUUL kits were purchased at a local tobacco store in Richmond, VA in February 2018; additional ‘Virginia Tobacco’ and ‘Cool Mint’ JUUL pods were purchased at a local retailer from September 2017 to June 2019. All products were charged prior to the start of the study session as indicated by product labelling. Product use consisted of one 10-puff ‘directed’ bout (30 s interpuff interval) and, after 25 min rest, a 90 min ad libitum bout. Blood was sampled via a catheter placed in a forearm vein before and immediately after each bout, heart rate and blood pressure were monitored continuously (heart rate and blood pressure data not reported), and expired air CO (Vitalograph; Lenexa, Kansas, USA) and subjective effects10 were measured before and after each bout. Participants were compensated US$100 after each session.
Blood plasma was analysed for nicotine concentration11 (LOQ=2 ng/mL) and values below the LOQ were replaced with 2 ng/mL.8–10 Statistical analyses (repeated measures analysis of variance, with Huynh-Feldt corrections) were performed using IBM SPSS (V.26.0). Post hoc testing for significant condition (OB, JUUL, IQOS) by time (predirected, postdirected, pre-ad lib, post-ad lib) interactions and main effects of condition and time were analysed using Holm-Sidak corrected t-tests.
Results
Participant characteristics
Thirteen men and five women (eight Caucasian, seven African-American, three other) completed the study. Participants’ mean (SD) age was 36.8 (9.3) years and they reported smoking a mean of 16.4 (5.1) cigarettes per day for 11.7 (8.9) years. Fifty-six per cent smoked menthol. The average machine-smoked nicotine yield of participants’ OB cigarettes was 0.94 (0.17) mg.12 Mean exhaled CO at screening was 21.1 (6.6) ppm.
Biomarkers
There was a significant condition by time interaction for plasma nicotine (F(6,96)=7.08, p<0.001). As table 1 shows, mean plasma nicotine concentration (n=17) increased significantly in all three conditions following the directed and the ad libitum bouts, relative to immediately before each bout (ts>4.25; ps<0.05). Mean plasma nicotine was significantly higher in OB relative to JUUL and IQOS following both bouts (ts>3.06; ps<0.05).
Means and SD for outcome variables by product type
There was a significant condition by time interaction for CO (F(6,102)=48.79, p<0.001). As table 1 shows, mean CO increased significantly for OB only after the directed bout and after the ad libitum bout (ts>5.87; ps<0.05); no significant increases in CO were observed for JUUL or IQOS. Mean CO concentrations following the directed and the ad libitum bouts were significantly higher for OB relative to JUUL and IQOS (ts>4.68; ps<0.05).
Subjective effects
We examined each subjective measure (Visual Analogue Scale items and the Questionnaire of Smoking Urges-Brief (QSU) factors 1 and 213) for evidence of suppression of tobacco/nicotine abstinence effects after each bout (n=17; see table 1). Mean scores for ‘Craving a cigarette/nicotine’ and ‘Urges to smoke’ were reduced in all three conditions following the directed bout and, for OB and IQOS, were reduced following the ad libitum bout (ts>2.54; ps<0.05). Mean scores for these two items were lower for OB relative to JUUL following the ad libitum bout (ts>2.83; ps <0.05) and mean score for ‘Urges’ was lower for OB relative to IQOS following the ad libitum bout (t(16)=2.14; p<0.05). Following the directed bout, mean scores for ‘Impatient’ and ‘Irritable’ were reduced for OB, JUUL and IQOS (ts>2.35; ps<0.05). Mean scores for ‘Anxious’ were reduced following both bouts for OB and JUUL (ts>2.77; ps <0.05). Mean scores for ‘Restless’ were reduced for OB and IQOS following the directed bout (ts>3.06; ps <0.05). Mean scores for ‘Difficulty concentrating’ were reduced for JUUL following both bouts and were reduced for OB following the ad libitum bout only (ts>2.56; ps <0.05). Mean scores for ‘Depression’ were significantly reduced from baseline prior to the ad libitum bout in the IQOS condition (t(16)=2.69; p<0.05). Mean scores for ‘Pleasant’ and ‘Satisfy’ were higher for OB than for JUUL and IQOS following both bouts (ts>2.51; ps <0.05). Mean scores for ‘Taste good’ were significantly higher for OB than for JUUL following the directed bout, and was higher for OB than IQOS following the ad libitum bout (ts>2.29; ps<0.05).
Mean QSU factor 1 scores were reduced for OB and IQOS following the directed bout and for OB, IQOS, and JUUL following the ad libitum bout (ts>2.78; ps <0.05). Mean factor 1 score was lower for OB relative to JUUL following the directed and ad libitum bouts (ts>2.51; ps <0.05). Mean factor 2 scores were reduced for OB and IQOS following the directed and ad libitum bouts (ts>2.81; ps<0.05).
Discussion
This study is one of the first independent examinations of JUUL/IQOS nicotine delivery in cigarette smokers with no prior JUUL or IQOS experience and it shows that OB cigarettes delivered more nicotine and suppressed tobacco/nicotine abstinence more effectively than JUUL or IQOS. JUUL delivered the least nicotine, in seeming contradiction to independent reports of its high nicotine yield with 4 s puffs3 and industry-sponsored reports of higher nicotine delivery with 3 s puffs.14 In the present study, the participants received no instructions regarding puff duration and, if they took ~2 s puffs as is typical of cigarette smokers,8 15 that shorter puff duration may explain the lower delivery reported here. Indeed, in a recent study, six experienced pod-mod users were able to obtain an average nicotine boost of 28.6 (9.8) ng/mL following 30 puffs over 10 min, with an average plasma nicotine concentration of 12.9 ng/mL at 4 min, consistent with the current results.16 Taken together, these results concerning JUUL’s nicotine yield and delivery highlight the need for continued work to characterise JUUL’s nicotine delivery profile (especially in JUUL-experienced individuals) as well as the need for puff topography measurement for this and other novel tobacco products and how they may change over time with experience.
IQOS is not the first product to use an electrical element to heat pressed tobacco: an earlier product of similar design (‘Accord’) was marketed nearly two decades ago.17 Relative to that earlier product, IQOS may deliver nicotine and suppress tobacco/nicotine abstinence effects more effectively.15 18 A recent independent study investigating the acute effects of IQOS and a tank-style ECIG (18 mg/mL, 8 W device) also found that combustible cigarettes suppressed tobacco abstinence symptoms more than ECIG or IQOS, although IQOS was more satisfying and provided more enjoyable throat sensations than ECIG.5 Notably, Accord did not substitute for cigarettes in cigarette smokers19 and the acceptability of IQOS as a cigarette substitute among long-term cigarette smokers is uncertain, as is its capacity to reduce the lethality of tobacco consumption.20–26 Notwithstanding that uncertainty and dearth of data informing what impact on public health IQOS may have, IQOS is now available in the US market, after FDA review of a premarket tobacco product application.
As novel tobacco products grow in popularity, independent research examining their nicotine and other toxicant delivery is required to inform regulation, and that research must take into account changes in user behaviour that might accompany greater experience with the product. Data generated in this manner can help to inform policy-makers who may be considering eliminating protonated nicotine and/or limiting the rate at which nicotine is emitted from tobacco products.27
What this paper adds
JUUL and IQOS are tobacco products that use electronic heaters to create an aerosol for user inhalation.
Limited data are available on JUUL and IQOS nicotine delivery and abstinence symptom suppression among cigarette smokers.
The current study is one of the first independent studies of the acute effects and nicotine delivery profile of JUUL and IQOS in cigarette smokers.
JUUL and IQOS deliver less nicotine and reduce tobacco abstinence symptoms to a lesser degree than own-brand cigarettes in smokers naïve to JUUL and IQOS.
Ethics statements
Ethics approval
Virginia Commonwealth University IRB HM20012013.
Acknowledgments
The success of this project would have not been possible without the support and contributions of many individuals. The authors would like to thank and recognise the contributions of Barbara Kilgalen, Janet Austin and Lauren Ratliff, who assisted with data collection and management.
This work has been presented previously at The Society for Research on Nicotine and Tobacco (SRNT) 2019 (San Francisco, California) 2018, SRNT Europe 2018 (Munich, Germany) and NIH Tobacco Regulatory Science Conference (TCORS) October 2018 (Bethesda, Maryland).
References
Footnotes
Contributors SM, AE, MC and AB were involved in writing this manuscript. ES and TE designed this study and contributed to the write up of this manuscript.
Funding This study was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number P50DA036105 and U54DA036105 and the Center for Tobacco Products of the US Food and Drug Administration.
Disclaimer The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Food and Drug Administration.
Competing interests TE is a paid consultant in litigation against the tobacco and electronic cigarette industry and is named on a patent for a device that measures the puffing behavior of ECIG users.
Provenance and peer review Not commissioned; externally peer reviewed.