Acute nicotine reinforcement requires ability to discriminate the stimulus effects of nicotine.

Abstract

This review of research on behavioral discrimination of nicotine and how it informs public health policy for reducing risk of tobacco dependence is adapted from Kenneth A. Perkins’s American Psychological Association Division 28 (Psychopharmacology and Substance Abuse) 2020 Med Associates Brady/Schuster Award Lecture. The author’s initial programmatic clinical research on nicotine is introduced, especially efforts to develop and validate a novel method of acute nicotine dosing. After the public health rationale for characterizing the discriminative stimulus effects of nicotine in humans are described, details from two separate programs of research on nicotine discrimination in humans are presented. The first, conducted with nicotine dosing by nasal spray, documented that humans could discriminate nicotine administered rapidly, examined nicotine’s neuropharmacological specificity, identified discrimination threshold dose in smokers and nonsmokers, and explored other conditions that might alter ability to discriminate its effects. The second, more recent program focused on threshold doses for discrimination of nicotine by cigarette smoking, a program that was very difficult to do until the past decade, and how nicotine’s self-reported “reward” and preference via choice behavior relate to its discriminability. Differences due to menthol and degree of tobacco dependence were also examined. For each of these two programs, the main findings of selected studies are noted, followed by very recent work on nicotine discrimination and choice that informs Food and Drug Administration’s efforts to formulate public policy to improve health and reduce the nearly half million American deaths per year due to persistent tobacco use.

The role of β-Nicotyrine in E-Cigarette abuse liability I: Drug Discrimination

“…Slower Nic metabolism is a risk factor for Nic dependence in naïve adolescents initiating cigarette smoking (Karp et al, 2006; for a review see The present findings show that b-Nic may slow Nic metabolism sufficiently to increase the potency of Nic (e.g., by lowering its discrimination threshold). Prior human laboratory work by Perkins, Sofuoglu, and colleagues has examined the reinforcement and discrimination thresholds for Nic (i.e., see reviews by Perkins et al, 2022, Sofuoglu & LeSage, 2012 and the general conclusions were that greater sensitivity to the interoceptive stimulus effects of Nic is associated with greater abuse liability of Nic (e.g., Perkins et al, 2018). They contend that the discrimination threshold is a stronger metric than that of the reinforcement threshold as the former is necessary for the latter to be observed (Perkins, 2022) and that it should be the target for tobacco control (Sofuoglu & LeSage, 2012).…”

“…Prior human laboratory work by Perkins, Sofuoglu, and colleagues has examined the reinforcement and discrimination thresholds for Nic (i.e., see reviews by Perkins et al, 2022, Sofuoglu & LeSage, 2012 and the general conclusions were that greater sensitivity to the interoceptive stimulus effects of Nic is associated with greater abuse liability of Nic (e.g., Perkins et al, 2018). They contend that the discrimination threshold is a stronger metric than that of the reinforcement threshold as the former is necessary for the latter to be observed (Perkins, 2022) and that it should be the target for tobacco control (Sofuoglu & LeSage, 2012). If the present findings are applicable to humans, it suggests that b-Nic should lower the Nic discrimination threshold and thus should result in greater abuse liability of ENDS products.…”