Identifying substances suspected of facilitating inhalation or increasing nicotine uptake as part of the enforcement of the Tobacco Products Directive.

Abstract

The Tobacco Products Directive 2014/40/EU (TPD) introduced rules prohibiting tobacco products and liquids for electronic cigarettes with nicotine which contain substances or additives that facilitate inhalation or nicotine uptake. However, this property has not been clearly defined. The present study proposes mechanisms of action to characterise this property, thereby supporting effective enforcement of the TPD. The first step consists of identifying the mechanisms of action that aim to increase the bioavailability of nicotine; to decrease the irritation or aversion related to nicotine; or to increase the concentration of nicotine in the aerosol. Other mechanisms of action were excluded as they do not specifically target nicotine or because they are aiming to increase the 'addictive effect' and should be treated as a separate issue. The second part of the process is to describe the mechanisms of action mentioned above, based on the available data. An extensive list of substances with nicotine inhalation facilitating properties is proposed, containing TRPM8 receptor agonists and β2-adrenoreceptor agonists. Further research on the properties of certain substances, including increased transbuccal permeability, pH alteration and bronchodilator effect, is also suggested.We recommend enforcing a ban on all the substances we listed in cigarettes, roll-your-own tobacco, cigars, cigarillos, pipe tobacco and water pipe tobacco. For vaping products, as menthol is one of the most used flavours by users wishing to quit, a benefit-risk balance of a ban on menthol and other TRPM8 receptor agonists in vaping products should be conducted before implementing it. However, the other substances listed should be banned.