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Cigarette smoking is overrepresented in populations with psychiatric conditions and socioeconomic disadvantage. Greater understanding of the role of reinforcement and nicotine dependence in smoking among vulnerable populations may facilitate development of better targeted interventions to reduce smoking. Prior research demonstrated that individual differences in the reinforcing value of smoking and nicotine-dependence severity predicted total nicotine-exposure in vulnerable populations. The present study uses multivariate regression to address two aims: (1) Quantify the degree to which the reinforcing value of smoking, assessed using the Cigarette Purchase Task (CPT), and dependence severity assessed using the Fagerström Test of Nicotine Dependence and Brief Wisconsin Inventory of Smoking Dependence Motives (B-WISDM) each account for individual differences in cotinine-plus-3'-hydroxycotinine (COT+3HC) levels. (2) Explore whether there is overlap in the variance accounted for by the CTP, FTND, and B-WISDM. Participants were 628 adults with co-morbid psychiatric conditions or socioeconomic disadvantage who smoked daily. The CPT, FTND, and B-WISDM models accounted for 23.76%, 32.45%, and 29.61% of the variance in COT+3HC levels, respectively. Adding CPT to the FTND model failed to increase the variance accounted for and adding it to the B-WISDM model did so by only 1.2% demonstrating considerable overlap in the variance in nicotine exposure levels accounted for by these three instruments. These results provide new knowledge on the relationship between individual differences in the reinforcing value of smoking and nicotine-exposure levels and suggest differences in reinforcing value may underpin a considerable portion of the variance in nicotine exposure accounted for by dependence severity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Risk for smoking increases in a summative manner corresponding to the number of co-occurring vulnerabilities present (cumulative vulnerability). We examined whether cumulative vulnerabilities moderate response to reduced nicotine content cigarettes in a secondary analysis of results from 775 participants in three 12-week randomized clinical trials examining research cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco). Participants were categorized as having 0-1, 2-3, or ≥ 4 cumulative vulnerabilities. Vulnerabilities included: rural residence, current substance use disorder, current affective disorder, low educational attainment, poverty, unemployment, physical disability. The primary outcome was total cigarettes per day (CPD) during Week 12; secondary outcomes included CPD across weeks, toxin exposure, dependence severity, craving/withdrawal (17 dependent measures). Results were analyzed using repeated measures analysis of covariance and growth-curve modeling. Total CPD during Week 12 increased as cumulative-vulnerability increased (P = 0.004), and decreased as nicotine content decreased (P < 0.001), with no significant interaction of cumulative vulnerability and dose (P = 0.67). Effects on other outcomes generally followed that same pattern. The only exception across the other outcomes was on Questionnaire-on-Smoking-Urges Factor-2 ratings for usual-brand cigarettes where cumulative vulnerability, dose, and time interacted (P = 0.007), with craving at the 0.4 and 2.4 mg/g doses decreasing over time, but inconsistently across vulnerability categories. Overall, we saw little evidence that cumulative vulnerabilities moderate response to reduced nicotine content cigarettes suggesting that a policy reducing nicotine content in cigarettes to minimally addictive levels could benefit even highly vulnerable smokers including those residing in rural or other regions with overrepresentation of co-occurring vulnerabilities. Clinicaltrials.gov identifiers: NCT02232737, NCT02250664, NCT02250534., (Copyright © 2021. Published by Elsevier Inc.)

Accumulating evidence suggests that the hypothetical Cigarette Purchase Task (CPT), especially its demand Intensity index (i.e., estimated cigarettes participants would smoke if free), is associated with individual differences in smoking risk. Nevertheless, few studies have examined the extent to which hypothetical CPT demand Intensity may differ from consumption when participants are provided with free cigarettes. That topic is the overarching focus of the present study. Participants were 745 adult smokers with co-morbid psychiatric conditions or socioeconomic disadvantage. CPT was administered for usual-brand cigarettes prior to providing participants with seven days of their usual-brand cigarettes free of cost and consumption was recorded daily via an Interactive Voice Response (IVR) System. Demand Intensity was correlated with IVR smoking rate (rs 0.670-0.696, ps < 0.001) but estimates consistently exceeded IVR smoking rates by an average of 4.4 cigarettes per day (ps < 0.001). Importantly, both measures were comparably sensitive to discerning well-established differences in smoking risk, including greater cigarettes per day among men versus women (F(1,732) = 18.74, p < 0.001), those with versus without opioid-dependence (F(1,732) = 168.37, p < 0.001), younger versus older adults (F(2,730) = 32.93, p < 0.001), and those with lower versus greater educational attainment (F(1,732) = 38.26, p < 0.001). Overall, CPT demand Intensity appears to overestimate consumption rates relative to those observed when participants are provided with free cigarettes, but those deviations are systematic (i.e., consistent in magnitude and direction, Fs all <1.63; ps > 0.19 for all interactions with subgroups). This suggests that demand Intensity was sensitive to established group differences in smoking rate, supporting its utility as an important measure of addiction potential., (Published by Elsevier Inc.)

We examined whether elucidating underpinning smoking motivation and related pharmacological processes enhances understanding of nicotine dependence among smokers from vulnerable populations. Data were obtained between Oct, 2016 and Sept, 2019 from 745 adult smokers with co-morbid psychiatric conditions or socioeconomic disadvantage at University of Vermont, Brown University, Johns Hopkins University. Smoking motivation was assessed using the Cigarette Purchase Task (CPT), a behavioral-economic task that models the relative reinforcing value of smoking under varying monetary constraint. Dependence severity was measured using the Heaviness of Smoking Index (HSI), Fagerström Test for Nicotine Dependence total scores (FTND), and FTND total scores minus items 1 and 4 (FTND 2,3,5,6 ). We also assessed associations between dependence severity and smoking motivation with nicotine levels and metabolism rate. Principal Component Analysis was used to examine the latent structure of the conventional five CPT indices; bivariate and multivariable modeling was used to test associations. Factor analysis resulted in a two-factor solution, Amplitude (demand unconstrained by price) and Persistence (price sensitivity). CPT latent factors were associated with each dependence-severity measure (ps ≤ 0.0001), with associations stronger for Amplitude than Persistence across each, especially HSI which was exclusively associated with Amplitude . Amplitude and each dependence measure were associated with nicotine intake (ps ≤ 0.0002); Persistence was not (p = .19). Demand Amplitude more than Persistence appears key to understanding individual differences in dependence severity. Regarding potential application, the results suggest a need for interventions that more effectively target demand Amplitude to make greater headway in reducing smoking in vulnerable populations. Trial Registration:clinicaltrials.gov identifiers: NCT02232737, NCT02250664, NCT02250534., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Cigarette preference increases as a function of greater nicotine content, but manipulating cost can shift preference. The aims of the present study are to model whether (1) the behavioral-economic metric unit price (cost/reinforcer magnitude) accounts for preference shifts and (2) whether preference shifts toward reduced nicotine content are associated with smoking reductions. In a multisite study between 2015 and 2016, 169 daily smokers from vulnerable populations completed two concurrent-choice conditions examining preference for smoking normal (15.8 mg/g) and reduced (0.4 mg/g) nicotine content cigarettes. In Condition 1, both products were available at 10 responses/choice. In Condition 2, availability of the 0.4 mg/g dose remained at 10 responses/choice while the 15.8 mg/g dose was available on a progressive-ratio (PR) schedule wherein response cost increased following each choice. Unit prices were calculated by dividing dose by response requirement. Results were analyzed using ANOVA and binomial tests (p < .05). Participants preferred the 15.8 over 0.4 mg/g dose in Condition 1, but shifted preference to the 0.4 mg/g dose in Condition 2 (p < .001) immediately before the point in the PR progression where unit price for 15.8 dose exceeded unit price for the 0.4 dose (p < .001). This shift was associated with a reduction in smoking (p < .001). The unit price of nicotine appears to underpin cigarette product preference and may provide a metric for predicting preference and potentially impacting it through tobacco regulations. These results also demonstrate that reduced compared to normal nicotine content cigarettes sustain lower smoking rates discernible even under acute laboratory conditions and in vulnerable populations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

This study examines whether tobacco dependence severity moderates the acute effects of reducing nicotine content in cigarettes on the addiction potential of smoking, craving/withdrawal, or smoking topography. Participants (N = 169) were daily smokers with mild, moderate, or high tobacco-dependence severity using the Heaviness of Smoking Index. Following brief abstinence, participants smoked research cigarettes varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg nicotine/g tobacco) in a within-subject design. Results were analyzed using repeated measures analysis of co-variance. No main effects of dependence severity or interactions with nicotine dose were noted in relative reinforcing effects in concurrent choice testing or subjective effects on the modified Cigarette Evaluation Questionnaire. Demand for smoking in the Cigarette Purchase Task was greater among more dependent smokers, but reducing nicotine content decreased demand independent of dependence severity. Dependence severity did not significantly alter response to reduced nicotine content cigarettes on the Minnesota Tobacco Withdrawal Scale nor Questionnaire of Smoking Urges-brief (QSU) Factor-2 scale; dependence severity and dose interacted significantly on the QSU-brief Factor-1 scale, with reductions dependent on dose among highly but not mildly or moderately dependent smokers. Dependence severity and dose interacted significantly on only one of six measures of smoking topography (i.e., maximum flow rate), which increased as dose increased among mildly and moderately but not highly dependent smokers. These results suggest that dependence severity has no moderating influence on the ability of reduced nicotine content cigarettes to lower the addiction potential of smoking, and minimal effects on relief from craving/withdrawal or smoking topography., (Copyright © 2018. Published by Elsevier Inc.)