A novel abuse liability assessment of e-cigarettes in young adults ii: Reinforcement enhancement and follow-up assessment.

A double-blind study was performed to test the abuse liability of electronic nicotine delivery systems (ENDS) in young adults; in particular, the influence of nicotine on reward sensitivity was assessed. A total of 53 healthy nonusers participated in experimental sessions during which they played a video game made available on a progressive ratio schedule of reinforcement and self-administered nicotine via ENDS. Participants were randomized into one of three groups. Two groups received either a dedicated concentration of nicotine (6 and 12 mg) or a placebo, and whether they received the placebo or their dedicated nicotine dose was randomly determined on a session-by-session basis to mask the sequencing of drug administration. The third group received only a 0 mg (placebo) vaping device during all sessions. In comparison to all placebo conditions, nicotine-induced reward sensitization was evidenced on behavioral measures of video game reinforcement, but not subjective appraisals of the vaping experience. A 1-month follow-up survey provided evidence that reinforcement enhancement by nicotine predicts increased abuse liability of ENDS. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A systematic review and meta-analysis of interventions to induce attempts to quit tobacco among adults not ready to quit.

The prevalence of past-year smoking cessation remains below 10% in the U.S. Most who smoke are not ready to quit in the near future. Cessation requires both (a) initiating a quit attempt (QA) and (b) maintaining abstinence. Most research has focused on abstinence among people already motivated to quit. We systematically reviewed interventions to promote QAs among people not motivated to quit tobacco. We searched PubMed, CENTRAL, PsycINFO, Embase, and our personal libraries for randomized trials of tobacco interventions that reported QAs as an outcome among adults not ready to quit. We screened studies and extracted data in duplicate. We pooled findings of the 25 included studies using Mantel-Haenszel random effects meta-analyses when ≥ 2 studies tested the same intervention. Most (24) trials addressed cigarettes and one addressed smokeless tobacco. Substantial heterogeneity among trials resulted in a series of small meta-analyses. Findings indicate varenicline may increase QAs more than no varenicline, n = 320; RR = 1.4, 95% CI [1.1, 1.7]; I² = 0%, and nicotine replacement therapy (NRT) may increase QAs more than no NRT, n = 2,568; RR = 1.1, 95% CI [1.02, 1.3]; I² = 0%. Pooled effects for motivational counseling, reduction counseling, and very low nicotine content cigarettes showed no clear evidence of benefit or harm. The evidence was judged to be of medium to very low certainty due to imprecision, inconsistency, and risk of bias, suggesting that further research is likely to change interpretation of our results. Findings demonstrate the need for more high-quality research on interventions to induce QAs among adults not ready to quit tobacco. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The interactive effects of JUUL flavor and nicotine concentration on addiction potential.

Prior research suggests that flavors can influence the pharmacological effects of nicotine. We used commercially available JUUL pods to examine whether preferred menthol versus tobacco flavor increased the addictive potential of nicotine per se. This study recruited 15 regular JUUL e-cigarette users to complete a 2 × 2 factorial crossover trial using an entirely remote video format. Participants completed a sampling baseline session to identify preferred JUUL flavor (menthol vs. tobacco) followed by four counterbalanced experimental sessions separated by ≥ 48 hr: (a) low-nicotine dose (3% JUUL)/nonpreferred flavor; (b) low dose/preferred flavor; (c) high-nicotine dose (5% JUUL)/nonpreferred flavor; and (d) high dose/preferred flavor. In each experimental session, participants completed a puffing procedure followed by subjective ratings of e-cigarette liking and wanting (ELW), urges, and reinforcement using a JUUL pod purchase task. There was a dose-by-flavor interaction for average ELW (F = 4.58, p = .041) in which ELW was significantly greater for the preferred than the nonpreferred flavor at the low-nicotine dose but not the high-nicotine dose. There were also dose-by-flavor interactions for pre- to post-puffing change in overall urge to vape (F = 5.97, p = .021) and urge strength (F = 4.96, p = .049), with greater reductions in overall urge/strength for the preferred compared to the nonpreferred flavor at the low but not the high dose. We found no significant interaction effects for purchase task outcomes. Using a fully remote experimental puffing procedure, our findings suggest preferred flavors increase the rewarding effects most for lower nicotine e-cigarettes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Potential effects of nicotine content in cigarettes on use of other substances.

A national nicotine reduction policy has the potential to reduce cigarette smoking and associated adverse health impacts among vulnerable populations. However, possible unanticipated adverse effects of reducing nicotine content in cigarettes, such as increasing the use of alcohol or other abused substances, must be examined. The purpose of this study was to evaluate the effects of exposure to varying doses of nicotine in cigarettes on use of other substances. This was a secondary analysis (n = 753) of three simultaneous, multisite, double-blind, randomized-controlled trials examining 12 weeks of exposure to study cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco) among daily smokers from three vulnerable populations: individuals with affective disorders (n = 251), individuals with opioid use disorder (n = 256), and socioeconomically-disadvantaged women of reproductive age (n = 246). Effect of study cigarette assignment on urine toxicology screens (performed weekly) and responses to drug and alcohol use questionnaires (completed at study weeks 6 and 12) were examined using negative binomial regression, logistic regression, or repeated measures analysis of variance, controlling for sex, age, and menthol status. The most common substances identified using urine toxicology included tetrahydrocannabinol (THC; 44.8%), cocaine (9.2%), benzodiazepine (8.6%), and amphetamines (8.0%), with 57.2% of participants testing positive at least once for substance use (27.3% if excluding THC). No significant main effects of nicotine dose were found on any of the examined outcomes. These results suggest that reducing nicotine content does not systematically increase use of other substances, even among individuals at increased risk of substance use. ClinicalTrials.gov Identifiers: NCT02232737, NCT2250664, NCT2250534.

Reinforcement enhancement by nicotine: A novel abuse-liability assessment of e-cigarettes in young adults.

Nicotine can act as a primary positive reinforcer, and as negative reinforcer to relieve withdrawal; we tested whether it can also enhance the reinforcing efficacy of non-drug reinforcers. Young-adult never-users were delivered nicotine via e-cigarette, and a videogame reinforcer was used to test nicotine enhancement. Three dose groups were tested (placebo-only, 6 or 12-mg nicotine), and participants returned to the lab for several sessions over the course of 1 month. Those in the two nicotine-dose groups received placebo on some occasions and nicotine on others; nicotine enhancement of the videogame reinforcer was assessed in a within-subjects fashion by comparing each of the two nicotine groups' dedicated nicotine dose to placebo. In the placebo-only group, progressive-ratio (PR) schedule breakpoints did not alter as a function of videogame exposure, suggesting that the videogame retained its basic-reinforcing properties throughout the study. For the two groups that received nicotine, both doses of nicotine increased PR-schedule breakpoints for the videogame reinforcer relative to the placebo condition. Although nicotine was associated with greater subjective evaluation of the enjoyment of the videogame, it was unrelated to the enjoyment of the e-cigarette device. No evidence was found that nicotine elevated either anhedonia or withdrawal symptoms in the timeframe of the study. The results provide initial evidence that nicotine enhancement, via electronic cigarettes, occurs in non-frequent users of nicotine products and may be a reason they can develop nicotine dependence in the absence of withdrawal and direct effects of nicotine. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Cumulative vulnerabilities as a potential moderator of response to reduced nicotine content cigarettes.

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.

Tobacco and Nicotine Use Among US Adult "Never Smokers" in Wave 4 (2016-2018) of the Population Assessment of Tobacco and Health Study.

INTRODUCTION: A common criterion for being labeled a "never smoker" is having smoked <100 lifetime cigarettes. This category is often used as an unexposed reference group to estimate the relative harm from cigarettes. We examined the amount of current and past cigarette and non-cigarette tobacco/nicotine use among adults who met this "never smoker" criterion. METHODS: We analyzed cross-sectional data from 17 179 adult "never smokers" (ie, reported <100 lifetime cigarettes) in Wave 4 (2016-2018) of the Population Assessment of Tobacco and Health (PATH) Study, a United States nationally representative sample. We used PATH-derived variables to describe "never smokers'" demographics as well as cigarette and non-cigarette tobacco/nicotine use. RESULTS: Approximately half of "never smokers" were young adults (49.3%). Most were white (68.6%) with some college or more (64.4%). Most "never smokers" had tried any cigarette or non-cigarette tobacco/nicotine in their lifetime (66.7%), 8.5% smoked cigarettes in the past 30 days, and 5.3% were current experimental (ie, some days or every day) cigarette smokers. By definition, "never smokers" reported smoking <100 lifetime cigarettes. One fifth (22.8%) had a lifetime history of established regular non-cigarette tobacco/nicotine use and 8.6% were current established regular non-cigarette tobacco/nicotine users. In total, 9.4% of "never smokers" were current experimental or established regular users of combustible tobacco. CONCLUSIONS: The 100-cigarette lifetime threshold includes substantial amounts of current and past tobacco use and thus does not represent lack of exposure to cigarette or non-cigarette tobacco. "Never smoker" reference groups may produce underestimates of the relative harms from cigarettes. IMPLICATIONS: The <100 lifetime cigarettes criterion may not capture what many would consider true "never smokers." Relying on the current definition of "never smokers" as a reference group will include a substantial number of those currently and recently using combustible tobacco and thus produce data that may underestimate the relative harm from cigarettes. Prospective longitudinal research is needed to compare how the 100-cigarette lifetime threshold versus other definitions of regular cigarette smoking differ in predictive validity of clinically meaningful outcomes and health harms to determine the optimal criteria to define established cigarette smoking.

Possible New Symptoms of Tobacco Withdrawal III: Reduced Positive Affect-A Review and Meta-analysis.

INTRODUCTION: Most descriptions of tobacco withdrawal have not changed in >30 years despite new research. This meta-analysis tested whether abstinence leads to decreased positive affect (PA) because abstinence-induced symptom changes are a core feature of the tobacco withdrawal syndrome. In addition, we examined whether reduced PA was due to withdrawal (ie, temporary decrease in a "U-shaped" curve) or offset (ie, return to baseline) effect. METHODS: Our main inclusion criterion was a prospective within-participant test of change in PA during abstinence conditions among people who smoke cigarettes daily who were not using a cessation medication. Our search of PubMed, PsycINFO, and personal libraries yielded a total of 32 tests with 2054 participants. RESULTS: There was a medium effect size indicating an overall decrease in PA following abstinence from cigarettes (Cohen's d = -0.40, 95% CI = -0.30 to -0.49). There was large heterogeneity (I2 = 70.7%). Most (79%) of the 24 trials that conducted significance tests reported that reduction in PA was significant. Seven tests were adequately designed to detect a withdrawal versus offset effect. Over half (57%) displayed a U-shaped curve for abstinence-induced change in PA indicative of a withdrawal symptom rather than offset effect. CONCLUSIONS: Abstinence from cigarettes is associated with a decrease in PA. Whether low PA should be added to withdrawal measures and diagnostic criteria requires replication of the time-course of change in PA and tests of whether abstinence-induced changes in PA and negative affect occur independently. IMPLICATIONS: Though there was substantial heterogeneity among trials, our findings suggest that (1) abstinence from cigarettes decreases positive affect and (2) this decrease may represent a withdrawal effect (vs. an offset effect). However, it is unclear whether abstinence-induced losses in positive affect are independent from increased negative affect.

Both reducing cigarettes per day and transitioning to very low-nicotine-content cigarettes decreases demand for usual-brand cigarettes.

Reducing cigarettes per day (CPD) and transitioning to very low-nicotine-content (VLNC) cigarettes appear to decrease nicotine dependence. Other well-accepted measures of the addictiveness of cigarettes involve behavioral economic simulation models, such as the cigarette purchase task (CPT), which characterizes the reinforcing efficacy of cigarettes. Currently it is unclear whether reducing CPD or reducing nicotine through VLNC cigarettes leads to greater reductions in the reinforcing efficacy of cigarettes. The current paper reports a secondary analysis of a 5-week, 2-arm unblinded randomized trial, in which participants were instructed to gradually reduce to 70%, 35%, 15%, and 3% of baseline nicotine over 4 weeks by either (a) reducing CPD (n = 32) or (b) switching to VLNC cigarettes (n = 36). Participants completed the CPT for their usual-brand cigarettes at baseline and again at a 1-month follow-up. Demand was significantly reduced for participants' usual-brand cigarettes in both the CPD, t(18) = 7.65, p < .0001, and the VLNC groups, t(18) = 7.39, p < .0001, from prereduction procedure to the 1-month follow-up. Maximum consumption at zero price (intensity), and maximum expenditure (Omax), were reduced significantly for both the CPD group, t(16) = 3.23, p = .005; t(16) = 3.71, p = .002, respectively, and the VLNC group, t(22) = 3.62, p = .002; t(22) = 3.14, p = .005, respectively, prereduction procedure to the 1-month follow-up. Thus, despite the different mechanisms by which the value of cigarettes was manipulated, both interventions reduced the reinforcing efficacy of cigarettes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Changes in Cigarette Consumption With Reduced Nicotine Content Cigarettes Among Smokers With Psychiatric Conditions or Socioeconomic Disadvantage: 3 Randomized Clinical Trials.

Importance: This study is part of a programmatic effort evaluating the effects of reducing nicotine content of cigarettes to minimally addictive levels. Objective: To examine whether very low-nicotine-content (VLNC) cigarettes decrease smoking rates and dependence severity among smokers with psychiatric disorders or socioeconomic disadvantage. Design, Setting, and Participants: These 3 randomized clinical trials were performed at the University of Vermont, Brown University, and Johns Hopkins University between October 2016 and September 2019. Participants received 12 weeks of exposure to study cigarettes with nicotine content ranging from levels representative of commercial cigarettes (15.8 mg nicotine/g tobacco) to less than a hypothesized addiction threshold (2.4 mg/g and 0.4 mg/g). Daily smokers from 3 at-risk populations participated: individuals with affective disorders, exemplifying smokers with mental illness; individuals with opioid use disorder, exemplifying smokers with substance use disorders; and women with high school educations or less, exemplifying smokers with socioeconomic disadvantage. Data were analyzed from September 2019 to July 2020. Interventions: Random assignment to 1 of 3 study cigarettes provided weekly at no cost for 12 weeks. Main Outcomes and Measures: The primary outcome was between-group differences in mean total cigarettes smoked daily (CPD) during week 12; secondary outcomes included CPD for study and nonstudy cigarettes and dependence severity across weeks analyzed using analysis of covariance, random coefficients growth modeling, or repeated measures analysis of variance. Results: A total of 775 participants were included (mean [SD] age, 35.59 [11.05] years; 551 [71.10%] women [owing to 1 population being exclusively women]); participants smoked a mean (SD) of 17.79 (9.18) CPD at study intake. A total of 286 participants were randomized to 0.4 mg/g, 235 participants were randomized to 2.4 mg/g, and 254 participants were randomized to 15.8 mg/g. Participants randomized to VLNC cigarettes had decreased mean [SEM] total CPD during week 12 across populations (Cohen d = 0.61; P < .001). At week 12, mean (SEM) CPD decreased to 17.96 (0.98) CPD in the 0.4 mg/g group and to 19.53 (1.07) CPD in the 2.4 mg/g group, both of which were significantly different from the 15.8 mg/g group (25.08 [1.08] CPD at week 12) but not each other (0.4 mg/g adjusted mean difference: -7.54 [95%CI, -9.51 to -5.57]; 2.4 mg/g adjusted mean difference: -5.34 [95% CI, 7.41 to -3.26]). Several secondary outcomes differed across populations randomized to VLNCs, including mean total CPD across weeks, with linear trends lower in participants receiving 0.4 mg/g (-0.28 [95%CI, -0.39 to -0.18]; P < .001) and 2.4 mg/g (-0.13 [95%CI, -0.25 to -0.01]; P < .001) doses compared with those receiving the 15.8 mg/g dose (0.30 [95% CI, 0.19 to 0.41]). Fagerström Test of Nicotine Dependence mean total scores were significantly lower in participants who received VLNCs (Cohen d = 0.12; P < .001), with those who received the 0.4 mg/g dose (mean [SD] score, 3.99 [0.06]; P < .001 vs 15.8 mg/g) or 2.4 mg/g dose (mean [SD] score, 4.07 [0.06]; P = .01 vs 15.8 mg/g) differing from those who received the 15.8 mg/g dose (mean [SD] score, 4.31 [0.06]) but not from each other. Conclusions and Relevance: These findings demonstrate that decreasing the nicotine content of cigarettes to very low levels reduced smoking rate and nicotine-dependence severity in these high-risk populations, effects that may facilitate successful cessation. Trial Registration: ClinicalTrials.gov Identifiers: NCT02232737, NCT02250664, NCT02250534.

Abuse liability of cigarettes with very low nicotine content in pregnant cigarette smokers.

The U.S. Food and Drug Administration has proposed reducing the nicotine content of cigarettes to a minimally-addictive level. To our knowledge, this study is the first to examine how pregnant smokers respond to very low nicotine content (VLNC) cigarettes. In Phase 1, participants blindly sampled two VLNC cigarettes (0.4 and 2.4 mg/g of tobacco) and their usual brand (UB) cigarette in separate sessions, then completed a behavioral economic simulation task and measures of subjective effects, craving/withdrawal, and smoking topography. Phase 2 directly compared the relative reinforcing effects of the cigarettes using concurrent choice testing. All possible dose-pair combinations were tested in separate sessions where puffs were earned ad libitum by clicking the code associated with their preferred cigarette 10 times. Phase 3 tested the 0.4 mg/g-UB dose-pair where UB puffs could be earned with a progressively incremented number of clicks (maximum 8400). Ten pregnant smokers in Burlington, VT and Baltimore, MD participated in 2017-2018. Regarding abuse liability, participants chose the 0.4-mg/g dose less than UB (22% vs. 78%) during concurrent choice testing and the 0.4-mg/g dose sustained less demand than the 2.4-mg/g and UB doses on the simulation task. Positive subjective effects were also lower for both VLNC cigarettes vs. UB. Each cigarette reduced nicotine craving/withdrawal and no significant changes indicative of compensatory smoking were noted. Reducing the nicotine content of cigarettes may decrease their abuse liability in pregnant smokers without causing untoward craving/withdrawal or compensatory smoking. Studies of extended exposure to VLNCs in pregnant women are warranted.

Relating individual differences in nicotine dependence severity to underpinning motivational and pharmacological processes among smokers from vulnerable populations.

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 (FTND2,3,5,6). 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.

Predictors of Smoking Cessation Attempts and Success Following Motivation-Phase Interventions Among People Initially Unwilling to Quit Smoking.

INTRODUCTION: Most people who smoke cigarettes are not willing (ie, not ready) to make a quit attempt (QA) at any given time. Unfortunately, interventions intended to increase QAs and the success of QAs are only modestly effective. Identifying processes leading to QAs and quitting success could guide intervention development. AIMS AND METHODS: This is a secondary analysis of a randomized factorial trial of 6 weeks of motivation-phase interventions among primary care patients (N = 517) who were initially unwilling to quit but were willing to reduce their smoking. Using logistic regression, we controlled for treatment condition and tested whether baseline or change in smoking-related constructs after 6 weeks of treatment predicted (1) making an at least 24 h QA between weeks 6 and 26 and (2) quitting success at week 26 (7-day point-prevalence abstinence among those who made a QA). Predictors included cigarettes/day, time to first cigarette, motivation to quit, quitting self-efficacy, anticipated urges to smoke if quit, positive affect, negative affect, and time spent around others who smoke. RESULTS: In multivariable models that included all smoking-related constructs, changes in the following variables predicted initiating a QA above and beyond other variables: greater baseline time to first cigarette (odds ratio [OR] = 1.60), increases in time to first cigarette (OR = 1.27), and increases in quitting self-efficacy (OR = 1.14). Increased motivation to quit predicted conversion of a QA into quitting success at 26 weeks (OR = 1.36). CONCLUSION: Predictors of making a QA differed from predictors of quitting success. Predictors of QAs and success could each serve as important treatment targets of motivation-phase interventions. IMPLICATIONS: Motivation-phase interventions for people initially unwilling to quit smoking cigarettes may be improved by striving to increase their (1) time to first cigarette and quitting self-efficacy to promote QAs and (2) motivation to quit to promote quit success. Future experimental tests of such interventions are needed to identify causal determinants of QAs and quitting success.

Initial Information on a Novel Nicotine Product.

BACKGROUND AND OBJECTIVES: This is the first study to assess the appeal and interest among adults in a new consumer tobacco product, ZYN. We also describe ZYN users, patterns of use, and reasons for use. METHODS: Two data sets, consisting of a ZYN-naive consumer panel (n = 5179) and ZYN users (n = 1266), were provided by Swedish Match North America. Descriptive, cross-sectional analyses and logistic regression assessed the perceptions of and likelihood of buying ZYN in the consumer panel and the characteristics of ZYN users. RESULTS: The majority of current smokeless tobacco (ST) users in the consumer panel found that ZYN was moderately-extremely appealing, while never and former tobacco users indicated much less interest; the former were more likely to buy ZYN than other groups. The highest percentage of ZYN users were former tobacco users (43%); very few were never users (4%). The most popular reason for using ZYN was "Less harmful to my health than other tobacco products," followed by "ease of use." DISCUSSION AND CONCLUSIONS: Nonusers of tobacco had very little interest in ZYN. ST users are not only more interested and likely to buy ZYN than other tobacco users, they were the largest group of regular users. SCIENTIFIC SIGNIFICANCE: The first assessment of a new nicotine product, ZYN, suggests that current and former tobacco users may perceive ZYN as a reduced-risk product. ZYN potentially could be used as a smoking/tobacco-cessation aid based on reasons of current users. (Am J Addict 2020;00:00-00).

Investigating tobacco withdrawal in response to reduced nicotine cigarettes among smokers with opioid use disorder and other vulnerabilities.

Individuals with opioid use disorder (OUD) have high prevalence of smoking and poor cessation outcomes. Data suggest that smokers with OUD may experience heightened nicotine reinforcement and more severe tobacco withdrawal compared to smokers without OUD. The Food and Drug Administration is currently considering reducing the nicotine content of cigarettes to reduce smoking prevalence and smoking-related disease. It is critical to understand the effects of reduced nicotine content cigarettes (RNCCs) on tobacco withdrawal in this subgroup. In this secondary analysis, we investigated the ability of RNCCs to attenuate acute tobacco withdrawal and craving severity in smokers with OUD versus those without substance use disorders (SUDs). Smokers maintained on methadone or buprenorphine (opioid-maintained [OM]; n = 65) versus without other SUDs (i.e., non-SUD; n = 135) completed 5 laboratory sessions wherein they smoked their usual brand (UB) or a research cigarette varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg/g of tobacco) under double-blind, acute abstinence conditions. Participants completed the Minnesota Tobacco Withdrawal Scale, including a desire to smoke (craving) item, before and every 15 min for 1 hr following smoking each cigarette. Tobacco withdrawal and craving did not differ significantly by OM status in response to UB or RNCCs. In addition to the Dose × Time interaction, greater depression and cigarette dependence consistently predicted withdrawal and craving (ps < .05). Across all cigarettes, tobacco withdrawal and craving did not significantly differ by OM status, suggesting that smokers receiving opioid agonist treatment may respond favorably to RNCCs. Additional studies with larger and more diverse samples are needed to address this question more definitively. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Withdrawal Symptoms From E-Cigarette Abstinence Among Adult Never-Smokers: A Pilot Experimental Study.

INTRODUCTION: Use of e-cigarettes among never-smokers has substantially increased; yet there are few descriptions of the consequences of such use. We assessed whether adult never-smokers can have withdrawal from cessation of e-cigarettes. METHODS: In an un-blinded pre-post clinical trial, 30 never-smoker daily e-cigarette users used their own nicotine-containing e-cigarette for 7 days followed by 6 days of biologically confirmed abstinence. Participants monitored symptoms of nicotine withdrawal nightly via an Interactive Voice Response system. They attended three lab visits/week to provide expired carbon monoxide and urine samples to determine compliance. FINDINGS: Abstinence increased all the DSM5 symptoms of tobacco withdrawal and this occurred in the majority of participants. The increase in severity of withdrawal was small and rarely impaired functioning. CONCLUSIONS: Our finding suggests that withdrawal symptoms can occur in never-smokers who stop e-cigarettes abruptly. However, the severity of withdrawal appears to be small and may not be of clinical or regulatory significance. Although our sample size was small and thus replication tests of our results are indicated, it may be prudent to warn never-smokers that withdrawal symptoms may occur. IMPLICATIONS: This study indicates that withdrawal symptoms can occur in never-smokers who are daily e-cigarette users. However, the severity of withdrawal from e-cigarette abstinence in never-smokers appears to be small and may not be of clinical or regulatory significance. Given our small sample size, replication of our results is warranted. Nevertheless, it might be prudent to warn never-smokers of addiction to e-cigarettes.Clinical Trial Registration = NCT02825459.