Harm from psychoactive drugs can also result for modes of drug delivery. The classic example here is nicotine—while nicotine itself is not a harm-free drug, over the last 100 years the harm has largely derived from its mode of delivery, smoked tobacco. Nicotine replacement therapies (gums, patches, etc.) have been used as treatment products to quit smoking rather than replacement products to smoked tobacco. Technological developments have now led to electronic nicotine delivery systems (ENDS; e-cigarettes) as widespread alternative delivery systems to smoked tobacco, with best estimates showing e-cigarettes to be 95 per cent less harmful to health than smoked cigarettes (see McNeill et al., 2015). There is much debate over their regulatory framework, bordering between regulations for medicinal products, tobacco products, or general product safety rules (see McNeill et al., 2015).
Margins of exposure analyses can be used to clarify the approach. For example, analyses of German e-cigarette liquids found that tobacco-specific toxicants and trace nicotine impurities were below levels likely to cause harm, suggesting that at least, from this perspective, e-cigarettes are likely to be less harmful than smoked tobacco (Hahn et al., 2014). Analyses of nicotine, glycerol, 1,2-propanediol, ethylene glycol, 1,3-propanediol, thujone, and ethyl vanillin found that nicotine was the only compound for which the complete distribution was below a MOE of 10, and on average below 0.1. From all other compounds, only ethylene glycol may have reached MOEs below 100 in about 50 per cent of cases and 1,2-propanediol in worst cases. This indicates that it is nicotine that is the toxic drug in e-cigarettes. Nicotine levels can be set, regulated, and monitored (see Box 4.3).
Opponents of ENDS are worried that ENDS are additive or gateway products to smoked tobacco, rather than replacement products (see discussion in Chapter 3). However, the evidence does not support this (see McNeill et al., 2015). And, in any case, incentives can be set (e.g. through price and availability) that steer use towards ENDS and away from smoked tobacco.