This is the first study to directly compare nicotine delivery from EC use between experienced and naïve EC users. A new-generation device was used, which has been previously shown to deliver nicotine more effectively compared to first-generation (cigarette-like) devices7. The study clearly showed that both groups obtain nicotine from EC use, however, faster absorption rate and higher plasma nicotine levels were observed in experienced compared to naïve users. It seems that this is partly explained by differences in puffing patterns between the two groups; in particular, smokers took shorter puffs compared to vapers and puff duration was independently associated with the elevation of plasma nicotine levels after 65 minutes of use.

New generation EC devices are predominantly used by dedicated users who, in most cases, are heavy ex-smokers2. The hypothesis that such devices deliver nicotine more efficiently compared to first-generation devices was confirmed in a recent clinical study which found higher plasma nicotine levels in experienced users when using a new-generation device compared to a “cigarette-like” product7. Subsequently, a laboratory study confirmed that elevating power levels leads to increased aerosol yield and nicotine delivery from the liquid to the aerosol13. Herein it was shown that naïve users are unable to obtain similar levels of nicotine compared to experienced users when using advanced devices. This was partly explained by differences in puff duration between the two groups. Smokers were using the EC in a similar puffing pattern as tobacco cigarettes, taking shorter puffs compared to experienced users. Similar observations were reported in a previous study of EC use topography8. In that study, vapers took 4.2 sec puffs, compared to 2.4 sec puffs observed in naïve users. In the present study vapers took somewhat shorter puffs, which can be explained by the higher EC power used in this study. However, considering the weak correlation between changes in plasma nicotine levels and puff duration, it seems that additional factors contribute to nicotine absorption. Such factors could be depth of inhalation and time of keeping the vapor inhaled.

Smoking is a difficult addiction to break. Tobacco cigarettes deliver nicotine very effectively, mostly in terms of speed of absorption14. Speed of delivery, as well as other substances in smoke which potentiate the addictive properties of nicotine15, contribute significantly to the dependence potential of tobacco cigarettes. It is reasonable to assume that alternative products would be more successful in substituting smoking if they could replicate the nicotine delivery potential of tobacco cigarettes. Randomized controlled studies evaluating the efficacy of ECs in substituting smoking have shown modest results16,17. One of the main reasons for this was assumed to be the low potential of the devices used in those studies to deliver nicotine to the user. Despite the fact that new-generation devices are more efficient, they still lag behind in speed of nicotine delivery compared to smoking, which typically raises plasma nicotine levels to 15 ng/mL or more within 5 minutes14. In naïve users, the lower potential of ECs to deliver nicotine is more prominent. A recent study showed enhanced nicotine intake after using first-generation EC device for 4 weeks5. By assessing patterns of use, our study confirms previous observations that there is a learning curve in the use of ECs, even when new-generation devices are used; experienced users use ECs more intensively compared to novice users8,17. Since less than 20% of smokers who try ECs progress to using them daily18,19, our results indicate that smokers need to be properly informed about the difference in characteristics of EC use compared to tobacco cigarettes in order to avoid any initial disappointment which would discourage further use and compromise successful smoking substitution or lead to dual use of tobacco cigarettes and ECs.

Some limitations apply to this study. Vapers used different equipment and liquid from what they were regularly using. It is possible that, by being more familiar, vapers would get higher plasma nicotine levels when using their own equipment. Moreover, we did not provide participants with a choice of different flavours, thus it is possible that some of them underused the EC because they did not like the taste of the liquid used in the study. All blood samples were obtained immediately after use, without any period of abstinence; therefore, we were unable to determine whether there is any delayed nicotine absorption, which would indicate absorption through the oral mucosa. However, a study evaluating first generation ECs showed no delayed absorption5; most likely, the same applies to use of newer-generation devices. Only puff number and duration was measured to assess patterns of use. In smoking, puff volume is also important in terms of nicotine delivery. However, Talih et al. found no effect of puff volume on nicotine delivery to the aerosol of ECs13. The potential of ECs to deliver nicotine within 5 minutes may have been underestimated due to the fact that participants were informed that they could vape ad lib for 65 minutes overall during the experimental session. If the protocol dictated EC use for 5 minutes only, with a subsequent abstinence period, it is possible that participants would have used the devices more intensively since they would have little time to satisfy their nicotine need, resulting in higher plasma nicotine levels. Moreover, they were not allowed to take more than 10 puffs during that period; ad lib use could have resulted to higher number of puffs taken during the 5 minute period, which could influence plasma nicotine levels. An 18 mg/mL nicotine containing solution was used in this study. Although it is possible to obtain and use liquid with higher levels of nicotine in the US, the European Union Tobacco Product Directive dictates a maximum limit of 20 mg/mL nicotine concentration in EC liquids sold within the European Union. This will be implemented from 2016 and is applicable to all products besides those which will obtain medicinal license; currently, no EC product has got medicinal license, due to the long-lasting and very expensive process. Our study indicates that this limit may be inadequate to fully satisfy the needs of smokers in terms of nicotine intake. Previous studies have shown that a substantial proportion of smokers need to use high nicotine-containing liquids in order to quit smoking2. However, the evolution of new products might result in better nicotine delivery from the liquid to the aerosol and faster nicotine absorption in the future, without the need to use higher nicotine concentration liquids. Although this could make ECs more addictive, it raises an important ethical issue of whether a product, which is probably beneficial for a part of the population (smokers), should be restricted (which could result in reduced efficacy as a smoking substitute) because some other parts of the population (non-smokers) decide to voluntarily adopt its use and perhaps becoming addicted to it20. Any regulation should be based on the assessment of the balance between any harm from use by non-targeted (non-smokers) versus the potential benefits from use by targeted population groups (smokers). More population studies are needed to assess this aspect, however, it is important to properly educate the society that ECs should be used as smoking substitutes and not as a new healthy habit for anyone to adopt. Finally, the equipment used in this study, although considered new-generation, is already outdated. EC technology is progressing at a fast pace and research is sometimes unable to follow this progress and assess the efficacy of such devices promptly. The battery device we used has been now substituted with a newer version generating more power, while newer-generation atomizers can withstand higher power levels and puff durations without resulting in the unpleasant taste associated with the dry-puff phenomenon8. This can lead to higher production of vapor and, thus, higher nicotine content in the aerosol of each puff.

In conclusion, new-generation ECs can effectively deliver nicotine, but at a slower rate and at lower levels in naïve compared to experienced users. Users should be properly informed at the initiation of EC use that nicotine intake will likely increase as they learn and adjust their use-patterns. Faster nicotine delivery is expected to increase the appeal of ECs to smokers and could make them more effective as smoking cessation tools, at the cost of potentially increasing their dependence potential.