An Inventory of Methods for the Assessment of Additive Increased Addictiveness of Tobacco Products: Table 1.

Abstract

Background:Cigarettes and other forms of tobacco contain the addictive drug nicotine. Other components, either naturally occurring in tobacco or additives that are intentionally added during the manufacturing process, may add to the addictiveness of tobacco products. As such, these components can make cigarette smokers more easily and heavily dependent.Efforts to regulate tobacco product dependence are emerging globally. Additives that increase tobacco dependence will be prohibited under the new European Tobacco Product Directive.Objective:This article provides guidelines and recommendations for developing a regulatory strategy for assessment of increase in tobacco dependence due to additives. Relevant scientific literature is summarized and criteria and experimental studies that can define increased dependence of tobacco products are described.Conclusions:Natural tobacco smoke is a very complex matrix of components, therefore analysis of the contribution of an additive or a combination of additives to the level of dependence on this product is challenging. We propose to combine different type of studies analyzing overall tobacco product dependence potential and the functioning of additives in relation to nicotine. By using a combination of techniques, changes associated with nicotine dependence such as behavioral, physiological, and neurochemical alterations can be examined to provide sufficient information.Research needs and knowledge gaps will be discussed and recommendations will be made to translate current knowledge into legislation. As such, this article aids in implementation of the Tobacco Product Directive, as well as help enable regulators and researchers worldwide to develop standards to reduce dependence on tobacco products.Implications:This article provides an overall view on how to assess tobacco product constituents for their potential contribution to use and dependence. It provides guidelines that help enable regulators worldwide to develop standards to reduce dependence on tobacco products and guide researches to set research priorities on this topic.

Brain Region-Specific nAChR and Associated Protein Abundance Alterations Following Chronic Nicotine and/or Menthol Exposure

“…Additionally, although nicotine is the primary addictive agent in tobacco products, other components, such as menthol, may impact levels, location, and function of proteins of interest for the study of addiction or tobacco product regulation. [64][65][66][67][68] We report, for the first time, a comprehensive investigation of β2 nAChR subunit levels in nine murine brain regions following chronic nicotine and (±)-menthol plus nicotine exposure and in five brain regions for (±)-menthol alone. The hypothalamus was the only region identified that had elevated β2 nAChR subunit levels after chronic (±)-menthol treatment as well as elevated β2 nAChR subunit levels with (±)-menthol plus nicotine treatment compared to both vehicle and nicotine alone.…”

Exploring Neurobehaviour in Zebrafish Embryos as a Screening Model for Addictiveness of Substances

“…Moreover, tobacco smoking is so addictive that 9.1% of teenagers met diagnostic criteria for nicotine dependence after smoking less than a single pack and nearly 60% became dependent after smoking five packs of cigarettes [ 4 ]. Even though nicotine is the main addictive compound in tobacco, other components and additives may also contribute to tobacco addiction [ 5 , 6 ]. For example, sugars can be naturally present and/or added to tobacco and are likely to contribute to dependence potential by contributing to the formation of aldehydes upon combustion [ 7 , 8 ].…”

Advances in Behavioral Laboratory Methods that Inform Tobacco Regulatory Science: A TCORS Working Group Special Issue

“…26–28 It should also be noted, however, that tobacco products and tobacco smoke can contain thousands of chemical constituents in addtion to nicotine, some of which may increase the potential for initiating tobacco product use and addiction. 29–31 For instance, menthol masks respiratory irritation produced by cigarette smoke, 32 may increase abuse liability of tobacco by acting as a conditioned reinforcer, 33 and may also increase the apparent dose of nicotine by inhibiting metabolism. 34,35 However, the utility of standard laboratory approaches that use cigarette smoking for studying the influence of nicotine and menthol interactions on smoking behavior is substantially constrained by the robust personal cigarette preferences within smokers.…”