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Background: Current FDA plans include proposed nicotine reduction mandates by the end of 2023. Most research on reduced nicotine cigarettes has been dose-blinded, while a mandate would be known to the public. Few laboratory studies have examined specifically how low nicotine content labeling impacts behavioral response. The purpose of this within-subject, balanced-placebo, human laboratory study was to evaluate the main and interactive effects of nicotine dose expectancy and dose reduction on cigarette reinforcement, withdrawal alleviation, and puff topography., Methods: Participants who smoke daily (N=21; 9 female) completed one practice and four experimental sessions in which expectancy (labeled "average" versus "very low" nicotine) and nicotine dose (0.80mg versus 0.03mg yield) were manipulated. Participants in acute withdrawal sampled experimental cigarettes followed by withdrawal alleviation and puff topography measures. Cigarette demand was measured using an incentivized purchase task. Analyses evaluated main and interactive effects of expectancy and nicotine dose., Results: Nicotine dose manipulation produced expected physiological effects (e.g., heart rate increases) and both reduced nicotine dose and expectation manipulations reduced perceived nicotine content. Expectation of reduced nicotine alone or in combination with reduced nicotine dose did not alter demand, withdrawal alleviation, or topography. Effective withdrawal alleviation was observed in all conditions., Conclusions: These data inform nicotine regulation policy by suggesting limited compensatory harms caused by reduced nicotine expectations. The minimal acute effects of reduced nicotine expectancy or exposure on demand suggests that reduced nicotine standards are likely to generate their greatest public health benefit through the slowing of newly initiating cigarette smoking., Competing Interests: Declaration of Competing Interest No conflicts of interest directly relevant to the conducted research are present. JCS has received research related funding from Canopy Growth Corporation and DynamiCare Health and consulting fees from Merck Corporation in the past three years. MWJ serves as consultant to AJNA Labs, AWAKN Life Sciences, Beckley Psytech Ltd., Clarion Clinics, Mind Medicine, Negev Capital, Otsuka Pharmaceutical Development & Commercialization, and Reunion Neurosciences, and has received research funding from Heffter Research institute, Fifth Generation, Inc., and Mydecine Innovations Group, Inc., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Reduction of nicotine content in tobacco products is a regulatory control strategy intended to decrease smoking dependence, and is hypothesized to produce gradual reductions of nicotine intake. Rats were initially trained to self-administer 0.06 mg/kg/infusion nicotine (Phase 1), which was followed by a threshold procedure to determine nicotine demand via a behavioral economics (BE) paradigm (Phase 2). Rats then either self-administered the training dose (high dose group), or were switched to a low dose of nicotine (0.001 mg/kg/infusion; low dose group) in Phase 3. Both groups then underwent a second threshold procedure and demand curves were re-determined (Phase 4). In Phase 5, responding for nicotine was extinguished over the course of 21 sessions. Cue-induced reinstatement was then evaluated (Phase 6). Rats in the low dose group maintained a steady amount of infusions, and thus, did not compensate for nicotine reduction. Rats in the low dose group also showed similar demand elasticity and nicotine seeking (Phase 6) compared to the high dose group, indicating that nicotine reduction did not decrease nicotine demand or seeking. Further, both groups displayed resistance to extinction, indicating that nicotine reduction did not facilitate extinction learning. These results suggest that although compensation of intake does not occur, decreasing the dose of nicotine does not alter nicotine reinforcement value or relapse vulnerability. Further, these results indicate persistence of nicotine-motivated behavior after self-administration of a low nicotine dose. Translationally, these results suggest that alternative strategies may be needed to achieve positive smoking cessation outcomes., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Published by Elsevier B.V.)

Background: The aim of the study was to assess young adult dual e-cigarette (EC) and combusted cigarette (CC) users' anticipated responses to a hypothetical very low nicotine content product standard and menthol ban in CC., Methods: Data came from 240 young adult (18-29 years) dual CC and EC users recruited via Amazon Mechanical Turk between June 20-22, 2017. Descriptive statistics were used to report sample characteristics. McNemar's tests were used to assess differences between product categories in terms of anticipated responses to hypothetical regulations., Results: A hypothetical very low nicotine content product standard in CC resulted in reported intentions to quit or reduce CC use and increase use of EC (p's<0.001). Hypothetical restrictions regarding the availability of menthol CC resulted in marginally significant reported intentions to increase EC use (p = 0.080). Anticipated responses to regulation were associated with baseline EC and CC use characteristics., Conclusions: This work provides preliminary evidence of the impact that regulations regarding nicotine content and menthol in CC may have on the use of EC among young adult dual users., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Mandating a reduction in the nicotine content of cigarettes to a minimally addictive level could dramatically reduce smoking rates in the US. However, little is known about the effects of reduced nicotine content cigarettes in adolescents., Methods: Following overnight abstinence, adolescent daily smokers (ages 15-19, n = 50) reported on their craving, withdrawal, and positive and negative affect pre- and post- ad lib smoking of one cigarette containing varying nicotine content (15.8, 5.2, 1.3 and 0.4 mg/g of tobacco) in the laboratory and reported their subjective evaluations of each cigarette. Carbon monoxide (CO) boost from pre- to post-cigarette was calculated to determine if lower-nicotine cigarettes led to differential acute changes in toxicant exposure., Results: All four nicotine cigarette types significantly reduced abstinence-induced craving, withdrawal, and negative affect (all p's < .05). Mixed models evaluating the effect of nicotine content, with nicotine dependence level and gender included as covariates, revealed a significant effect of nicotine content on craving and subjective evaluations: higher nicotine content resulted in greater reductions in craving and increases in both positive and negative subjective evaluations. There were no significant effects of nicotine dose on withdrawal symptoms, negative affect, or CO boost., Conclusions: These results suggest that lower nicotine cigarettes might result in reduced abuse liability compared to higher nicotine content cigarettes due to reduced positive subjective effects, while still reducing withdrawal, in adolescents. These results highlight the potential feasibility of this policy approach and support continued research on how a nicotine reduction policy may affect adolescent smoking patterns., (Copyright © 2018 Elsevier B.V. All rights reserved.)