Let us review a series of data concerning nicotine delivery from electronic cigarettes. The findings are conflicting, but not because of errors in the individual studies. Rather, the differences reflect the models used (laboratory versus naturalistic behavioral models), as well as differences in the human model being studied (initiation of use versus established, continuous use).
The first two studies were conducted in the laboratory, using a fixed nicotine-exposure protocol, in tobacco smokers who were not accustomed to using e-cigarettes.
In the first study (Vansickel), plasma nicotine levels were compared after: (a) smoking a tobacco cigarette containing 0.8 mg of nicotine; (b) taking 10 puffs from a loaded e-cigarette; and (c) taking puffs from an unlit cigarette. The results showed that nicotine levels with the e-cigarette were very low (2.2–3.5 ng/mL versus 8.7–20 ng/mL with tobacco), only slightly higher than those obtained by puffing on an unlit cigarette.
The second study (Bullen) compared 5 minutes of tobacco cigarette smoking, 5 minutes of e-cigarette use, and 20 minutes using a nicotine inhaler, with plasma nicotine levels measured one hour later. Here again, the e-cigarette produced levels of 1.3 ng/mL, compared with 13.4 ng/mL for the tobacco cigarette and 2.1 ng/mL for the inhaler.
In the third study, by Etter and Bullen,¹ cotinine levels—which are more or less equivalent in blood and saliva—were measured in the saliva of smokers accustomed to using e-cigarettes. The levels found were similar to those known to occur in tobacco smokers (322 ng/mL among the heaviest users, 141 ng/mL among moderate users, and 13 ng/mL among inconsistent users) and higher than those resulting from NRT (nicotine replacement therapy in various forms: patches, gum, tablets, etc.).
This study examined experienced and regular e-cigarette users, who reported taking between 5 and 1,000 puffs per day (25th–75th percentile: 100–400 puffs; mean 250 ± 205 SD). The cartridges had an average nicotine concentration of 18 mg/mL, and participants used an average of five cartridges per day. Subjects had not taken nicotine orally for at least the preceding 48 hours and had not smoked tobacco for at least 20 days. Almost all were former smokers, except for one participant who smoked one tobacco cigarette per day (the participants had been abstinent from tobacco for an average of 4.2 months). They had been using e-cigarettes for approximately three months on average (25th–75th percentile: 45 days–10 months; range: 16 days–3 years).
The last study certainly helps explain the results of the efficacy study examining tobacco smoking control in nicotine-dependent subjects who began using e-cigarettes. In that study, the six-month results were clearly positive: an 88% reduction in the number of cigarettes smoked, with stable abstinence achieved by 22.5% of participants, while the remainder used both e-cigarettes and tobacco. It is difficult to believe that a result of this magnitude, observed not after a few days but after six months, could be explained by a “placebo” effect or simply by replacing the ritual of smoking with a cigarette that releases virtually no nicotine, almost like an unlit cigarette. Moreover, it would make little sense to use a nicotine-containing liquid only to obtain virtually no nicotine delivery. One might just as well use a nicotine-free e-cigarette. Certainly, in the first laboratory study, the minimal nicotine levels obtained with the e-cigarette corresponded to only a minimal reduction in the desire to smoke, as would be expected.
Etter and Bullen conclude that variables associated with self-directed e-cigarette use result in nicotine levels that are very different from those produced by controlled laboratory exposure involving fixed quantities and regular intervals.
It should also be considered that some smokers may use e-cigarettes and tobacco cigarettes concurrently, resulting in nicotine levels higher than those obtained from e-cigarettes alone.
All of this is also consistent with theoretical calculations concerning nicotine delivery. If one calculates that, for every 1 mg of nicotine in the liquid, a three-second puff at a flow rate of 0.166 L/sec delivers 0.0031 mg of nicotine, then a liquid containing 18 mg, under the same conditions, delivers 0.0243 mg per puff. Considering that, in real-world use, the number of puffs ranges from 5 to 1,000 per day, with a median of 250, nicotine delivery therefore ranges from 0.12 mg to 24.4 mg per day (half of established e-cigarette users fall around 6.075 mg). Clearly, if someone takes a few puffs and then nothing for 45 minutes, followed by another few puffs, and so on, nicotine levels will remain low and a cartridge will last a long time. In reality, however, this pattern occurs only in some users.
After all, it would be strange to develop a cigarette that delivers nicotine if the resulting exposure were more or less equivalent to smoking an unlit cigarette.
The laboratory study is valid in itself, but it is not suitable for illustrating what happens in a real smoker using the device freely, and especially not in a nicotine-dependent smoker. After experiencing an almost negligible nicotine stimulus with the first few puffs, a nicotine-dependent smoker may either:
a) return to tobacco cigarettes after a while; or
b) attempt to inhale more intensively, continuously, and deeply in order to obtain higher nicotine levels.
The important difference, however, is that nicotine delivery remains different: instead of occurring as a “spike,” it occurs gradually. Thus, the final nicotine levels may be similar in a continuous user, but they remain relatively stable with an e-cigarette rather than fluctuating, with peaks and declines, as occurs with tobacco cigarettes.
This difference may help the smoker keep the desire for tobacco cigarettes suppressed, in much the same way as occurs with treatments for dependence on other substances, and with treatments for nicotine dependence itself using the nicotine-mimetic drug varenicline.
References
Etter J-F. Bullen C. Saliva cotinine levels in users of electronic cigarettes. European Respiratory Journal. 2011;38(5):1219–20.
Vansickel AR, Weaver MF, Eissenberg T. Clinical laboratory assessment of the abuse liability of an electronic cigarette. Addiction. 2012 Aug;107(8):1493–500.
Vansickel AR, Eissenberg T. Electronic cigarettes: effective nicotine delivery after acute administration. Nicotine & Tobacco Research. 2013 Jan;15(1):267–70.
Fagerström KO, Hughes JR, Rasmussen T, Callas PW. Randomised trial investigating effect of a novel nicotine delivery device (Eclipse) and a nicotine oral inhaler on smoking behaviour, nicotine and carbon monoxide exposure, and motivation to quit. Tobacco Control. 2000 Sep;9(3):327–33.
Bullen C, McRobbie H, Thornley S, Glover M, Lin R, Laugesen M. Effect of an electronic nicotine delivery device (e-cigarette) on desire to smoke and withdrawal, user preferences and nicotine delivery: randomised cross-over trial. Tobacco Control. 2010 Apr;19(2):98–103.
Goniewicz ML, Kuma T, Gawron M, Knysak J, Kosmider L. Nicotine levels in electronic cigarettes. Nicotine & Tobacco Research. 2013 Jan;15(1):158–66.