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).

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).

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.

Potential Moderating Effects of Psychiatric Diagnosis and Symptom Severity on Subjective and Behavioral Responses to Reduced Nicotine Content Cigarettes.

INTRODUCTION: Given FDA's authority to implement a cigarette nicotine reduction policy, possible outcomes of this regulation must be examined, especially among those who may be most affected, such as those with comorbid psychiatric disorders. METHODS: In this secondary analysis of a multisite, randomized, clinical laboratory study, we used analyses of variance to examine the effects of nicotine dose (0.4, 2.4, 5.2, and 15.8 mg/g of tobacco), depressive and anxiety diagnoses (depression only, anxiety only, both, or neither), and depressive and anxiety symptom severity on cigarette choice, smoke exposure, craving, and withdrawal across three vulnerable populations: socioeconomically disadvantaged women of reproductive age, opioid-dependent individuals, and those with affective disorders (n = 169). RESULTS: Diagnosis and symptom severity largely had no effects on smoking choice, total puff volume, or CO boost. Significant main effects on craving and withdrawal were observed, with higher scores in those with both anxiety and depression diagnoses compared with depression alone or no diagnosis, and in those with more severe depressive symptoms (p's < .001). These factors did not interact with nicotine dose. Cigarettes with <15.8 mg/g nicotine were less reinforcing, decreased total puff volume, and produced significant but lower magnitude and shorter duration reductions in craving and withdrawal than higher doses (p's < .01). CONCLUSIONS: Reducing nicotine dose reduced measures of cigarette addiction potential, with little evidence of moderation by either psychiatric diagnosis or symptom severity, providing evidence that those with comorbid psychiatric disorders would respond to a nicotine reduction policy similarly to other smokers. IMPLICATIONS: Thus far, controlled studies in healthy populations of smokers have demonstrated that use of very low nicotine content cigarettes reduces cigarette use and dependence without resulting in compensatory smoking. These analyses extend those findings to a vulnerable population of interest, those with comorbid psychiatric disorders. Cigarettes with very low nicotine content were less reinforcing, decreased total puff volume, and produced significant but lower magnitude and shorter duration reductions in craving and withdrawal than higher doses. These nicotine dose effects did not interact with psychiatric diagnosis or mood symptom severity suggesting that smokers in this vulnerable population would respond to a nicotine reduction strategy similarly to other smokers.

Evaluating the utility of the modified cigarette evaluation questionnaire and cigarette purchase task for predicting acute relative reinforcing efficacy of cigarettes varying in nicotine content.

BACKGROUND: Nicotine is the addictive component in cigarettes that maintain cigarette smoking that subsequently leads to morbidity and mortality. Methods for assessing the abuse liability of cigarettes are essential to inform new tobacco product standards. This secondary analysis evaluated the utility of one subjective effects measure, the modified Cigarette Evaluation Questionnaire (mCEQ), and one behavioral economic task, the Cigarette Purchase Task (CPT), for predicting acute relative reinforcing efficacy measured by concurrent choice Self-Administration (SA). METHODS: Smokers (N = 169) belonging to one of three vulnerable populations participated in a multi-site, double-blind study evaluating research cigarettes with varying levels of nicotine (0.4, 2.4, 5.2, 15.8 mg/g). Participants sampled cigarettes and completed the mCEQ and CPT. In subsequent sessions, cigarette preference was assessed using a concurrent choice SA procedure. Mixed-model repeated measures analysis of variance tests were used to evaluate the utility of the mCEQ subscales and CPT indices for predicting preference for the higher compared to lower nicotine content cigarettes. In addition, stepwise regressions were used to determine which subscales and indices independently predicted concurrent choice SA. RESULTS: Greater increases on the Satisfaction and Enjoyment of Respiratory Tract Sensations mCEQ subscales independently predicted higher dose preference in concurrent choice testing. Elasticity was the only CPT index that predicted choice. However, its predictive utility differed by dose among opioid-maintained individuals. CONCLUSION: The mCEQ and CPT predict behavioral measures of relative reinforcing efficacy as assessed in concurrent choice SA, with the mCEQ Satisfaction and Enjoyment of Respiratory Tract Sensations subscales being the strongest independent predictors.

Prevalence of withdrawal symptoms from electronic cigarette cessation: A cross-sectional analysis of the US Population Assessment of Tobacco and Health.

Electronic cigarette use can produce rapid and high levels of nicotine and thus could produce or maintain a physical dependence on nicotine. No experimental and limited observational studies have tested whether cessation of e-cigarettes is associated with withdrawal symptoms. To examine withdrawal from electronic cigarettes and compare it to that from tobacco cigarettes, we searched the US Population Assessment of Tobacco and Health Survey to locate successful and unsuccessful attempts to stop electronic or tobacco cigarettes. We examined electronic cigarette-only users, tobacco cigarette-only users and dual users. A minority of e-cigarette users who stopped/reduced e-cigarettes reported withdrawal symptoms but reported fewer symptoms than tobacco cigarette users who stopped/reduced tobacco cigarettes. E-cigarette withdrawal was not significantly greater in those who tried but were unable to stop e-cigarettes. In dual users, continued tobacco use appeared to reduce e-cigarette withdrawal but the opposite was not true. Given our small sample size and use of retrospective recall, an experimental test of e-cigarette abstinence is needed to better describe the severity of electronic cigarette withdrawal.

Associations of Proposed Relative-Risk Warning Labels for Snus With Perceptions and Behavioral Intentions Among Tobacco Users and Nonusers.

INTRODUCTION: The US Food and Drug Administration can require changes in warning statements for modified risk tobacco products. We report an independent analysis of a consumer perception survey sponsored by Swedish Match as part of a Modified Risk Tobacco Product application to change warning labels for Swedish snus products. METHODS: The survey exposed each of 4324 daily exclusive cigarette smokers, 1033 daily smokeless tobacco users, 1205 daily other tobacco users, 726 former users, and 5915 triers/never users to one of four current warnings and two proposed relative-risk labels (No tobacco product is safe, but this product presents lower risks to health than cigarettes, or No tobacco product is safe, but this product presents substantially lower risks to health than cigarettes) for snus. Descriptive and logistic regression analyses examined four outcomes: believability, harmfulness, motivation to use, and intention to buy snus. RESULTS: Compared with the current not-safe-alternative warning, adult tobacco users who viewed the proposed labels perceived them as less believable, perceived snus as less harmful and were more likely to use and buy snus. The proposed labels had no impact on former smokers' likelihood to use and buy snus; triers/never users viewing the substantially lower risk label were more likely to buy snus. CONCLUSIONS: Tobacco users viewing the proposed labels perceived snus as less harmful than cigarettes and may be more likely to use and buy snus. If labeling changes lead to increased snus use and cigarette reduction or abstinence, public health may benefit. If the opposite occurs, public health could suffer.

National Institutes of Health Funding for Tobacco Versus Harm From Tobacco.

INTRODUCTION: Previously, the author documented that, even though tobacco-related diseases accounted for 20% of US deaths, in 1995 the National Institutes of Health (NIH) expended only 1.1% of its budget on tobacco research. The current analysis is a replication test of this result and adds other outcomes and comparisons. METHODS: The author obtained NIH funding information for tobacco, alcohol, and drug use and for obesity for each year between 2007 and 2014 from Project Reporter and compared these to the total NIH budget and to measures of disease burden. RESULTS: NIH allocated $321 million for tobacco research in 2014. The percent of the NIH budget dedicated to tobacco was 1.3% in 2014 and has not changed since 1995; similar rates for alcohol, drug, and obesity problems in 2014 were 1.8%, 3.3%, and 3.8%. The ratio of spending to mortality from a risk factor was substantially less for tobacco compared to alcohol or obesity problems (0.07 vs. 0.60 and 0.30). CONCLUSION: These results replicate our earlier findings. Tobacco research continues to be underfunded at the NIH compared to its disease burden in the United States and to NIH funding for other behavioral risk factors.

The day-to-day process of stopping or reducing smoking: a prospective study of self-changers.

INTRODUCTION: Almost all descriptions of attempts to quit smoking have focused on what happens after an abrupt quit attempt and end once a smoker relapses. The current study examined the day-to-day process preceding a quit or reduction attempt in addition to the daily process after a failure to quit or reduce. METHODS: We recruited 220 adult daily cigarette smokers who planned to quit abruptly, to quit gradually, to reduce only, or to not change on their own. Participants called a voice mail system each night for 28 days to report cigarette use for that day and their intentions for smoking for the next day. No treatment was provided. RESULTS: Three main findings emerged: (a) The large majority of participants did not show a simple pattern of change but rather showed a pattern of multiple transitions among smoking, abstinence, and reduction over a short period of time; (b) most of those who reported an initial goal to quit abruptly actually reduced; and (c) daily intentions to quit strongly predicted abstinence, while daily intentions to reduce weakly predicted reduction. DISCUSSION: We conclude that the day-to-day process of attempts to change smoking among nontreatment seekers is much more dynamic than previously thought. This suggests that extended treatment beyond initial lapses and relapses and during postcessation reduction may be helpful.

Treatment seeking for smoking cessation among young adults.

Young adult smokers (18-24 year olds) do not seek treatment for smoking cessation as often as older smokers. Two commonly hypothesized reasons for this are that younger smokers are not aware of treatments or cannot afford them. The State of Vermont provides free smoking cessation treatment, and most young smokers are aware of this; thus, we tested whether young adult smokers from Vermont would still underutilize treatment via a secondary analysis of the population-based 2005 VT Adult Tobacco Survey. Young adult smokers from Vermont were less likely to have used medication (24% vs. 58%; relative risk = 0.42) or psychosocial (28% vs. 53%; relative risk = 0.54) treatment than middle-aged smokers (25-44 year olds). We conclude that reasons other than awareness and cost cause young adult smokers to not seek treatment.

Interest in treatments to stop smoking.

We surveyed 884 Vermont (VT) tobacco smokers by random digit dialing to determine past and future use of treatment. Among those who had recently attempted to quit, 61% had ever used a treatment, 21% had ever used a psychosocial treatment, and 57% had used a medication. Among those who planned to quit in the next month, 68% stated they would use a treatment, 35% would use a psychosocial treatment, and 62% would use a medication. The major predictors of past or future use of treatment were greater cigarettes per day, older age, being a woman, and seeing a health professional. Although this survey suggests many smokers have used or plan to use a smoking cessation treatment, program data indicate less than 10% of VT smokers who try to quit use the state quitline, counseling, or free medication provision. Why smokers do not use these treatments needs to be determined.