This is the first study that has compared the effect of using first- vs. new-generation EC devices on nicotine absorption. An 18 mg/ml nicotine-containing liquid was used, which is a popular “strength” consumed by experienced vapers and is close to the maximum level set by the European Commission regulatory proposal. Experienced vapers were recruited, who use the EC devices more intensively compared to novice users7. The results of the study showed that new-generation devices with high wattage output to the atomizer resulted in higher plasma nicotine levels compared to first-generation devices. However, both devices delivered to the bloodstream far lower nicotine compared to a tobacco cigarette.

ECs are the only nicotine delivery devices that resemble the motion and behavioral patterns of cigarette smoking. Although the psycho-behavioral part of smoking is an important part of the overall addiction to smoking16, nicotine delivery still plays a major role. Smoking characteristically delivers significant amounts of nicotine to the blood stream at a fast rate17. This is probably the main reason for making it the most reinforcing and dependence-producing form of nicotine administration17,18, although recent data suggest that other substances in tobacco cigarette may reinforce the addictive properties of nicotine19. Studies have shown that the vast majority of EC users continue to use nicotine-containing liquids despite having quit smoking for several months2,10,11. Therefore, it seems that nicotine is important in ECs' success as smoking substitutes. In this study a liquid with 18 mg/ml nicotine concentration was chosen, based on previous findings from our group showing that this is approximately the level of nicotine concentration needed for experienced vapers to consume 1 mg of nicotine in 5 minutes (which is similar to the level of nicotine in the smoke of one cigarette when smoked according to ISO 3308)7. Despite that, the main findings herein showed that such a liquid is insufficient to deliver nicotine to the blood stream as rapidly as smoking. In fact, it took about 35 minutes of vaping with the new-generation device at high wattage in order to obtain plasma levels similar to smoking one cigarette in 5 minutes. The first-generation device was even less efficient in nicotine delivery; even 65 minutes of ad lib vaping was insufficient to deliver to the bloodstream nicotine at levels similar to smoking. This was reflected in participants' answers to questionnaires, showing that satisfaction and craving reduction was higher after using the new- compared with the first-generation device. Moreover, better nicotine delivery may be the reason why new-generation devices are more popular in dedicated users, most of which have quit smoking by using ECs10,11. Considering that it is reasonable to expect EC users to self-titrate nicotine intake in a way similar to smoking20, this study indicates that there is an inherent inability of the EC to deliver nicotine to the blood stream at levels similar to tobacco cigarettes within the same time-period of use, although a previous study from our group showed that an 18 mg/ml liquid would theoreticaly be adequate for that in terms of liquid consumption7. Possible reasons for these findings may be that nicotine delivered to the EC aerosol is not absorbed from the lungs but from the oral mucosa. Therefore, nicotine absorption would be expected to occur at a similar rate to nicotine-replacement therapies (NRTs). Moreover, a significant part of nicotine deposited to the oral mucosa is expected to be swallowed, with subsequent first-pass metabolism to the liver which reduces bio-availability21. Another possibility is that the vehicle of nicotine delivery (liquid droplets of propylene glycol and glycerol) may negatively interact with nicotine absorption from the lungs compared to the particulate matter, which is the delivery-vehicle of nicotine in smoking. More studies are needed to define the reason for this lower rate of absorption from ECs. The new-generation device was more effective in this study because the higher amount of energy delivered to the atomizer results in higher amount of liquid aerosolized per puff, while first-generation devices deliver far lower energy and do not have an internal current stabilizer which maintains constant energy delivery until the battery is discharged. Due to this, it is reasonable to expect that new-generation devices may be more effective as smoking substitutes compared to first-generation devices. Two randomised studies evaluating the efficacy of EC use in smoking cessation have used first-generation devices22,23. New-generation devices seem more promising because they deliver nicotine more effectively and this should be evaluated in future studies. In any case, findings from this study indicate that ECs may also have less addictive properties and lower abuse liability, similar to what has been observed with NRTs24, due to the slow rate of nicotine absorption. This has been specifically observed in a study by Vansickel et al25. Herein, participants reported lower dependence to ECs compared to smoking, however the retrospective nature of the answers for smoking could have biased the results.

The European Commission has recently released a proposal that the highest permissible levels of nicotine concentration in liquids used for ECs will be 20 mg/ml5. The decision was based on the level of liquid consumption from 5 minutes of use6,7, but did not take into consideration that consumption is different from absorption; the main factors associated with the effects of nicotine are the levels in the bloodstream and the speed of absorption. Results of this study show that such nicotine concentration would be insufficient to deliver nicotine at levels similar to tobacco cigarettes unless ECs are used continuously for a long time. Moreover, the incidence of nicotine overdose or intoxication from EC use can be virtually excluded. Adopting the 20 mg/ml as the highest level of nicotine content in EC liquids might significantly reduce the efficacy of ECs to substitute smoking and will especially affect first-generation devices which are more popular, more attractive to first-time users (smokers) due to their resemblance to cigarettes and easier to use compared to new-generation devices. Based on the results of this study, showing very low levels of nicotine absorption from using ECs in a similar way to smoking one tobacco cigarette, it seems that nicotine levels in EC liquids should be close to 50 mg/ml in order to approximate nicotine delivery from smoking. This could also result in reduced daily EC use and liquid consumption, since the amount of nicotine needed by each user could be obtained by reducing the time and intensity of EC use. Clinical studies should be performed assessing the efficacy and speed of nicotine delivery by using higher nicotine-containing liquids. There is a possibility that using higher nicotine-containing liquids may elevate the addictive potential of ECs; however, considering that there is currently minimal adoption of EC use by non-smokers adults and youngsters11, it is reasonable to expect that the current proposal will reduce the effectiveness of ECs in substituting smoking while no beneficial effect to other population groups will be observed. Obviously, careful monitoring of use by these population groups is warranted; however, considering the current situation, a strict regulation banning the sales of ECs to minors would be more appropriate rather than adopting upper limits in nicotine content that would potentially reduce the efficacy of ECs to substitute smoking.

In conclusion, new-generation EC devices delivering higher energy to the atomizer seem to be more effective than first-generation devices in nicotine delivery to the user and in reducing cravings for nicotine. However, both types of devices were significantly less effective in nicotine delivery compared to tobacco cigarettes when an 18 mg/ml nicotine containing liquid is used. It is reasonable to assume that nicotine levels in EC liquids should be considerably higher in order to improve their effectiveness in nicotine delivery, which is expected to make them more successful as smoking substitutes.