Relationships Between the Nicotine Metabolite Ratio (NMR) and Laboratory Assessments of Smoking Reinforcement and Craving Among Adults in a Smoking Cessation Trial.

INTRODUCTION: People who metabolize nicotine more quickly are generally less successful at quitting smoking. However, the mechanisms that link individual differences in the nicotine metabolite ratio (NMR), a phenotypic biomarker of the rate of nicotine clearance, to smoking outcomes are unclear. We tested the hypotheses that higher NMR is associated with greater smoking reinforcement, general craving, and cue-induced cigarette craving in a treatment-seeking sample. METHODS: Participants were 252 adults who smoke cigarettes enrolled in a randomized controlled smoking cessation trial (NCT03262662) conducted in Buffalo, New York, USA. Participants completed the Choice Behavior Under Cued Conditions (CBUCC) paradigm, a laboratory choice procedure, ~1 week before the first cessation treatment visit, at which time a saliva sample was collected for NMR assessment. On each CBUCC trial, participants reported cigarette craving during cue presentation (cigarette, water) and spent $0.01-0.25 for a chance (5%-95%) to sample the cue (1 puff, sip), providing measures of smoking reinforcement (spending for cigarettes vs. water), general cigarette craving (averaged across cigarette and water cues), and cue-specific craving (cigarette craving during cigarette vs. water cues). RESULTS: As observed in prior work, the NMR was significantly higher among white and female participants. As expected, both spending and cigarette craving were significantly greater on cigarette compared to water trials. However, contrary to our hypotheses, higher NMR was not associated with greater smoking reinforcement, general craving, or cue-specific craving. CONCLUSIONS: The present data do not support that smoking reinforcement or craving are related to nicotine metabolism among individuals seeking to quit smoking. IMPLICATIONS: Though greater smoking reinforcement, general craving, and cue-specific craving are hypothesized to be linked to faster nicotine metabolism, there was no evidence of such relationships in the present sample of adults seeking to quit smoking. Further research, including replication and consideration of alternate hypotheses, is warranted to elucidate the mechanisms by which the NMR is related to smoking cessation.

Evaluating Declines in Compliance With Ecological Momentary Assessment in Longitudinal Health Behavior Research: Analyses From a Clinical Trial.

BACKGROUND: Ecological momentary assessment (EMA) is increasingly used to evaluate behavioral health processes over extended time periods. The validity of EMA for providing representative, real-world data with high temporal precision is threatened to the extent that EMA compliance drops over time. OBJECTIVE: This research builds on prior short-term studies by evaluating the time course of EMA compliance over 9 weeks and examines predictors of weekly compliance rates among cigarette-using adults. METHODS: A total of 257 daily cigarette-using adults participating in a randomized controlled trial for smoking cessation completed daily smartphone EMA assessments, including 1 scheduled morning assessment and 4 random assessments per day. Weekly EMA compliance was calculated and multilevel modeling assessed the rate of change in compliance over the 9-week assessment period. Participant and study characteristics were examined as predictors of overall compliance and changes in compliance rates over time. RESULTS: Compliance was higher for scheduled morning assessments (86%) than for random assessments (58%) at the beginning of the EMA period (P<.001). EMA compliance declined linearly across weeks, and the rate of decline was greater for morning assessments (2% per week) than for random assessments (1% per week; P<.001). Declines in compliance were stronger for younger participants (P<.001), participants who were employed full-time (P=.03), and participants who subsequently dropped out of the study (P<.001). Overall compliance was higher among White participants compared to Black or African American participants (P=.001). CONCLUSIONS: This study suggests that EMA compliance declines linearly but modestly across lengthy EMA protocols. In general, these data support the validity of EMA for tracking health behavior and hypothesized treatment mechanisms over the course of several months. Future work should target improving compliance among subgroups of participants and investigate the extent to which rapid declines in EMA compliance might prove useful for triggering interventions to prevent study dropout. TRIAL REGISTRATION: ClinicalTrials.gov NCT03262662; https://clinicaltrials.gov/ct2/show/NCT03262662.

Stability of Varenicline Concentration in Saliva Over 21 Days at Three Storage Temperatures.

INTRODUCTION: Varenicline is the most efficacious drug for smoking cessation; saliva varenicline concentrations can be useful for the evaluation of adherence in smoking cessation trials. Saliva is a useful noninvasive matrix for mail-in specimen collection, if stable. We investigated the stability of varenicline in saliva at different storage temperatures simulating the time it takes to mail in a sample. METHODS: We evaluated the concentrations of varenicline, nicotine, cotinine, 3'-hydroxycotinine, and 3'-hydroxycotinine/cotinine (3HC/COT) ratio in quality control saliva samples (and after repeated freezing and thawing), and in smokers' saliva samples, stored for up to 21 days at room temperature (~25°C), 4°C, and -80°C. RESULTS: In saliva quality control samples, concentrations of varenicline, nicotine, cotinine, 3'-hydroxycotinine, and 3HC/COT remained unchanged and showed little within-sample variation (CV ≤ 5.5%) for up to 21 days at the three storage temperatures; they were also not altered after three thaw-freeze cycles. In smokers' saliva, a significant main effect of storage duration, but not temperature, was observed for varenicline, cotinine, and 3'-hydroxycotinine, but not for nicotine or the 3HC/COT ratio. However, these changes were within analytical (i.e., equipment) variation resulting in little within-sample variation (CV ≤ 5.8%) for all analytes in smokers' saliva. CONCLUSIONS: Varenicline, the other analytes, and the 3HC/COT ratio remained stable in saliva during storage for 21 days at all temperatures tested and after repeated freezing and thawing with only minor changes in concentration over time. These findings support the potential use of mail-in approach for saliva samples in varenicline smoking cessation clinical trials. IMPLICATIONS: Assessing saliva varenicline concentrations can be useful for the evaluation of adherence in smoking cessation trials. Saliva is a noninvasive matrix suitable for mail-in specimen collection. This is the first investigation of stability of varenicline in saliva. Varenicline, nicotine, cotinine, 3'-hydroxycotinine, and 3HC/COT were stable in saliva for up to 21 days at room temperature (~25°C), 4°C, and -80°C, supporting the use of a mail-in approach for saliva specimen in smoking cessation trials.

A Psychometric Evaluation of the Stanford Expectations of Treatment Scale (SETS) in the Context of a Smoking Cessation Trial.

INTRODUCTION: Although treatment outcome expectancies (TOEs) may influence clinical outcomes, TOEs are rarely reported in the smoking cessation literature, in part because of the lack of validated measures. Therefore, we conducted a psychometric evaluation of TOEs scores with the Stanford Expectations of Treatment Scale (SETS) in the context of a smoking cessation clinical trial. METHODS: Participants were 320 adults enrolled in a randomized controlled trial of extended versus standard pre-quit varenicline treatment for smoking cessation (clinicaltrials.gov ID: NCT03262662). Across an 8-week treatment period, we examined the nature and stability of the factor structure using confirmatory factor analysis (CFA), evaluated discriminant validity by examining correlations with abstinence self-efficacy and positive/negative affect (PA/NA), and assessed internal consistency and test-retest reliability of SETS scores. RESULTS: CFAs supported a 2-factor structure that was stable (ie, invariant) across weeks. Positive and negative TOEs were each reflected in three-item subscales that exhibited acceptable to excellent internal consistency (Cronbach's alphas ≥ .77). Positive and negative TOEs were modestly correlated with PA and NA (all |rs| <.27, p < .05). Positive TOEs, but not negative TOEs, were moderately correlated with abstinence self-efficacy (rs = .45 to .61, p < .01). Both positive and negative TOEs scores demonstrated moderate test-retest reliability between assessments (rs = .54 to .72). CONCLUSIONS: SETS scores generally reflect a valid and reliable assessment of positive and negative TOEs in a sample of adults enrolled in a smoking cessation trial. The SETS appears to be a reasonable option for assessing TOEs in future smoking treatment studies. IMPLICATIONS: Assessments of treatment outcome expectancies are rarely reported in the smoking cessation literature. The present results support the validity and reliability of the SETS scores among adults seeking treatment for their smoking behavior.

Evaluating Treatment Mechanisms of Varenicline: Mediation by Affect and Craving.

INTRODUCTION: Negative reinforcement models posit that relapse to cigarette smoking is driven in part by changes in affect and craving during the quit attempt. Varenicline may aid cessation by attenuating these changes; however, this mediational pathway has not been formally evaluated in placebo-controlled trials. Thus, trajectories of negative affect (NA), positive affect (PA), and craving were tested as mediators of the effect of varenicline on smoking cessation. AIMS AND METHODS: Secondary data analysis was conducted on 828 adults assigned to either varenicline or placebo in a randomized controlled trial for smoking cessation (NCT01314001). Self-reported NA, PA, and craving were assessed 1-week pre-quit, on the target quit day (TQD), and 1 and 4 weeks post-TQD. RESULTS: Across time, NA peaked 1-week post-quit, PA did not change, and craving declined. Less steep rises in NA (indirect effect 95% CI: .01 to .30) and lower mean craving at 1-week post-quit (CI: .06 to .50) were mediators of the relationship between varenicline and higher cessation rates at the end of treatment. PA was associated with cessation but was not a significant mediator. CONCLUSIONS: These results partially support the hypothesis that varenicline improves smoking cessation rates by attenuating changes in specific psychological processes and supported NA and craving as plausible treatment mechanisms of varenicline. IMPLICATIONS: The present research provides the first evidence from a placebo-controlled randomized clinical trial that varenicline's efficacy is due, in part, to post-quit attenuation of NA and craving. Reducing NA across the quit attempt and craving early into the attempt may be important treatment mechanisms for effective interventions. Furthermore, post-quit NA, PA, and craving were all associated with relapse and represent treatment targets for future intervention development.

Testing alternative cascades from internalizing and externalizing symptoms to adolescent alcohol use and alcohol use disorder through co-occurring symptoms and peer delinquency.

Given the equivocal literature on the relationship between internalizing symptoms and early adolescent alcohol use (AU) and AU disorder (AUD), the present study took a developmental perspective to understand how internalizing and externalizing symptoms may operate together in the etiology of AU and AUD. We pit the delayed onset and rapid escalation hypothesis (Hussong et al., 2011) against a synthesis of the dual failure model and the stable co-occurring hypothesis (Capaldi, 1992; Colder et al., 2013, 2018) to test competing developmental pathways to adolescent AU and AUD involving problem behavior, peer delinquency, and early initiation of AU. A latent transactional and mediational framework was used to test pathways to AUD spanning developmental periods before AU initiation (Mage = 11) to early and high risk for AUD (Mage = 14-15 and Mage = 17-18). The results supported three pathways to AUD. The first started with "pure" externalizing symptoms in early childhood and involved multiple mediators, including the subsequent development of co-occurring symptoms and peer delinquency. The second pathway involved stable co-occurring symptoms. Interestingly, chronically elevated pure internalizing symptoms did not figure prominently in pathways to AUD. Selection and socialization effects between early AU and peer delinquency constituted a third pathway.

Comparing the Rate of Nicotine Metabolism Among Smokers With Current or Past Major Depressive Disorder.

BACKGROUND AND OBJECTIVES: Persons with current or past major depressive disorder (MDD) vs those without have higher smoking rates. The nicotine metabolite ratio (NMR) represents variation in the rate of nicotine metabolism and has been associated with smoking behaviors and response to tobacco treatments. We compared NMR between smokers with current or past MDD (MDD+) vs smokers without MDD (MDD-). We also assessed correlates of NMR and compared withdrawal and craving between MDD+ and MDD- smokers. METHODS: Using baseline data from two clinical trials and propensity score weighting based on sex, race, body mass index, and smoking rate, we compared NMR between MDD+ (N = 279) and MDD- (N = 1575) smokers. We also compared groups on and nicotine withdrawal and craving. RESULTS: Mean NMR (ß = -.02, 95% confidence interval [CI]: -0.05 to 0.01, P = .13) and the distribution of smokers across NMR quartiles (odds ratio [OR] = 0.76, 95% CI: 0.50 to 1.16, P = .21) were similar between MDD+ and MDD- samples. This relationship was not affected by antidepressant medication. In the MDD+ sample, African Americans had significantly lower mean NMR, while older smokers and smokers with lower education had higher mean NMR (Ps < .05). MDD+ smokers had significantly higher withdrawal and craving than MDD- smokers (Ps < .05). DISCUSSION AND CONCLUSIONS: While variability in NMR may not explain differences in smoking rates between MDD+ and MDD- smokers, MDD+ smokers report increased withdrawal and craving. SCIENTIFIC SIGNIFICANCE: In this first study to assess NMR among MDD+ smokers, the findings underscore the need to address withdrawal and craving within smoking cessation treatments for those with MDD. (Am J Addict 2021;00:00-00).

Withdrawal Symptom, Treatment Mechanism, and/or Side Effect? Developing an Explicit Measurement Model for Smoking Cessation Research.

INTRODUCTION: Assessment of withdrawal symptoms, treatment mechanisms, and side effects is central to understanding and improving smoking cessation interventions. Though each domain is typically assessed separately with widely used questionnaires to separately assess each domain (eg, Minnesota Nicotine Withdrawal Scale = withdrawal; Questionnaire of Smoking Urges-Brief = craving; Positive and Negative Affect Schedule = affect; symptom checklist = side effects), there are substantial problems with this implicit "one questionnaire equals one construct" measurement model, including item overlap across questionnaires. This study sought to clarify the number and nature of constructs assessed during smoking cessation by developing an explicit measurement model. METHODS: Two subsamples were randomly created from 1246 smokers in a clinical trial. Exploratory and confirmatory factor analyses were conducted to identify and select a model that best represented the data. Measurement invariance was assessed to determine if the factors and their content were consistent prior to and during the quit. Improvement in construct overlap within this model was compared against the implicit measurement model using correlational analyses. RESULTS: A 5-factor measurement model composed of negative affect, somatic symptoms, sleep problems, positive affect, and craving fits the data well prior to and during quitting. All factor content except somatic symptoms was consistent over time. Correlational analyses indicated that the 5-factor model attenuated construct overlap compared to the implicit model. CONCLUSIONS: The models generated from data-driven approaches (eg, the 5-factor model) reduced overlap and better represented the constructs underlying these measures. This approach created distinct, stable constructs that span over measures of side effects and potential treatment mechanisms. IMPLICATIONS: This study demonstrated that measures assessing treatment mechanisms, withdrawal symptoms, and side effects contain problematic overlap that reduces the clarity of these key constructs. The use of data-driven approaches showed that these measures do not map on to their posited latent constructs (eg, the Minnesota Nicotine Withdrawal Scale does not yield a withdrawal factor). Rather, these measures form distinct, basic processes that may represent more meaningful constructs for future research on cessation and treatment. Assessments designed to individually examine these processes may improve the study of treatment mechanisms.

The development of inhibitory control in adolescence and prospective relations with delinquency.

INTRODUCTION: Despite the central role of inhibitory control in models of adolescent development, few studies have examined the longitudinal development of inhibitory control within adolescence and its prospective association with maladaptive outcomes. The current study evaluated: 1) growth in inhibitory control from early- to middle-adolescence, and 2) the relation between inhibitory control and later delinquency. METHODS: Participants included 387 parent-child dyads (11-13 years old at Wave 1; 55% female; USA). Across three annual assessments, teens completed the Stop Signal Task (SST), and parents completed the Inhibitory Control subscale of the Early Adolescent Temperament Questionnaire-Revised. Teens self-reported their delinquent behaviors in early (Mage = 12.1) and middle adolescence (Mage = 14.1) and emerging adulthood (Mage = 18.2). RESULTS: Latent growth curve models indicated that SST performance improved curvilinearly from early to middle adolescence (ages 11-15), with growth slowing around middle adolescence. However, no growth in parent-reported inhibitory control was observed. Lower task-based and parent-reported inhibitory control in early adolescence predicted greater increases in delinquency from middle adolescence to emerging adulthood. However, rate of growth in task-based inhibitory control was unrelated to later delinquency. CONCLUSIONS: This longitudinal study provides a novel examination of the development of inhibitory control across early and middle adolescence. Results suggest that the degree to which inhibitory control confers risk for later delinquency may be captured in early adolescence, consistent with neurodevelopmental accounts of delinquency risk. Differences across assessment tools also highlight the need for careful measurement considerations in future work, as task-based measures may be better suited to capture within-person changes over time.

How do stimulant treatments for ADHD work? Evidence for mediation by improved cognition.

BACKGROUND: Stimulant medications such as methylphenidate (MPH) are the frontline treatment for Attention-Deficit/Hyperactivity Disorder (ADHD). Despite their well-documented efficacy, the mechanisms by which stimulants improve clinical outcomes are not clear. The current study evaluated whether MPH effects on classroom behavior were mediated by improved cognitive functioning. METHODS: Children with ADHD (n = 82; 9-12 years old) participated in a week-long summer research camp, consisting of cognitive testing, classroom periods, and recreational activities. After a baseline day, participants completed a 3-day randomized, double-blind, placebo-controlled trial of MPH (at doses approximating 0.3 and 0.6 mg/kg of immediate-release MPH dosed TID). Cognitive domains included inhibitory control (Stop Signal Task and prepulse inhibition of startle), attention (Continuous Performance Task and reaction time variability), and working memory (forward and backward spatial span). Clinical outcomes included math seatwork productivity and teacher-rated classroom behavior. A within-subjects path-analytic approach was used to test mediation. MPH-placebo and dose-response contrasts were used to evaluate drug effects. RESULTS: Methylphenidate improved seatwork productivity and teacher ratings (ds = 1.4 and 1.1) and all domains of cognition (ds = 0.3-1.1). Inhibitory control (Stop Signal Task, SST) and working memory backward uniquely mediated the effect of MPH (vs. placebo) on productivity. Only working memory backward mediated the impact of MPH on teacher-rated behavior. The dose-response (0.6 vs. 0.3 mg/kg) effects were more modest for clinical outcomes (ds = 0.4 and 0.2) and cognition (ds = 0-0.3); there was no evidence of cognitive mediation of the clinical dose-response effects. CONCLUSIONS: These findings are novel in demonstrating that specific cognitive processes mediate clinical improvement with stimulant treatment for ADHD. They converge with work on ADHD theory, neurobiology, and treatment development in suggesting that inhibitory control and working memory may be mechanisms of stimulant treatment response in ADHD. More work is necessary to evaluate the degree to which these findings generalize to chronic treatment, a broader array of clinical outcomes, and nonstimulant treatments.

Facilitated Extinction Training to Improve Pharmacotherapy for Smoking Cessation: A Pilot Feasibility Trial.

Introduction: Varenicline reduces smoking satisfaction during the pre-cessation run-in period, which may contribute to extinction of cravings and smoking behavior. Research indicates that efficacy is enhanced when the run-in period is increased from 1 to 4 weeks, providing a longer extinction opportunity. We hypothesized that efficacy could be further enhanced by harnessing basic and applied research on extinction. We developed a pre-cessation extinction-facilitating intervention and tested its feasibility in a pilot trial. Methods: The facilitated extinction (FE) intervention comprised brief counseling and workbook-recommending strategies to maximize extinction processes during the run-in, including instructions to smoke at a normal rate across contexts and cues, and use of an extinction cue to enhance generalization. Participants were randomly assigned to one of three varenicline interventions: standard (1-week run-in), extended (4-week run-in), and extended + FE. Interventions were delivered prior to the target quit date (TQD). Assessments were conducted in weeks 1 and 4 pre-TQD and 1 and 3 months post-TQD, with focus on feasibility indices. Results: Recruitment and retention goals were met (N = 58). Treatment satisfaction was high across groups. The majority of FE participants adhered to instructions and maintained their usual smoking rate during the run-in period. Greater decreases in craving and smoking satisfaction were observed among participants in both extended groups versus the standard group (p < .005). Conclusions: Feasibility was demonstrated. Participants adhered to the FE intervention, thereby optimizing the number and variety of extinction trials. Findings support testing the novel FE smoking cessation intervention in a fully powered trial. Implications: This study expands the research on the clinical benefits of extending the pre-cessation run-in period of varenicline. It introduces the hypothesis that further benefit might be achieved by translating basic behavioral research, as well as cue-exposure research and therapy for other disorders, to improve the extinction and generalization processes thought to underlie much of varenicline's effect. A FE intervention was developed and found acceptable to smokers and feasible to implement in a research setting. The study sets the stage for a subsequent randomized controlled trial.

Health Equity and Decentralized Trials.

This Viewpoint discusses the proliferation of decentralized clinical trials during the COVID-19 pandemic and the need for rigorous studies to inform whether decentralized approaches promote or prevent access to clinical trials for people facing health disparities.

The Prospective Association Between Internalizing Symptoms and Adolescent Alcohol Involvement and the Moderating Role of Age and Externalizing Symptoms.

BACKGROUND: As predicted by self-medication theories that drinking is motivated by a desire to ameliorate emotional distress, some studies find internalizing symptoms (e.g., anxiety, depression) increase risk of adolescent drinking; however, such a risk effect has not been supported consistently. Our prior work examined externalizing symptoms as a potential moderator of the association between internalizing symptoms and adolescent alcohol use to explain some of the inconsistencies in the literature. We found that internalizing symptoms were protective against early adolescent alcohol use particularly for youth elevated on externalizing symptoms (a 2-way interaction). Our sample has now been followed for several additional assessments that extend into young adulthood, and the current study tests whether the protective effect of internalizing symptoms may change as youth age into young adulthood, and whether this age-moderating effect varied across different clusters of internalizing symptoms (social anxiety, generalized anxiety, and depression). Internalizing symptoms were hypothesized to shift from a protective factor to a risk factor with age, particularly for youth elevated on externalizing symptoms. METHODS: A community sample of 387 adolescents was followed for 9 annual assessments (mean age = 12.1 years at the first assessment and 55% female). Multilevel cross-lagged 2-part zero-inflated Poisson models were used to test hypotheses. RESULTS: The most robust moderating effects were for levels of alcohol use, such that the protective effect of all internalizing symptom clusters was most evident in the context of moderate to high levels of externalizing problems. A risk effect of internalizing symptoms was evident at low levels of externalizing symptoms. With age, the risk and protective effects of internalizing symptoms were evident at less extreme levels of externalizing behavior. With respect to alcohol-related problems, findings did not support age moderation for generalized anxiety or depression, but it was supported for social anxiety. CONCLUSIONS: Findings highlight the importance of considering the role of emotional distress from a developmental perspective and in the context of externalizing behavior problems.

Probing the Behavioral and Neurophysiological Effects of Acute Smoking Abstinence on Drug and Nondrug Reinforcement During a Cognitive Task.

INTRODUCTION: Smoking abstinence is theorized to increase smoking reinforcement and decrease nondrug reinforcement. A separate literature demonstrates the detrimental effects of abstinence on cognition. The present study integrates these two areas by examining the separate and combined effects of reinforcement and smoking abstinence on behavior and a neurophysiological index of response monitoring (ie, error-related negativity [ERN]) during a cognitive task. METHODS: After a screening visit, adult smokers attended two laboratory visits, once while smoking and once while abstinent. Participants completed a flanker task under cigarette-, money-, and no-reinforcement conditions. The initial 15 participants had an easier reaction time (RT) requirement; to ensure sufficient error rates for ERN computation, a harder RT deadline was employed for the remaining 21 participants. RESULTS: Smoking abstinence reduced speeded accuracy and ERN amplitude only among participants tested with the harder RT deadline. Cigarette and money reinforcement each increased speeded accuracy and ERN amplitude compared to no reinforcement. The effect of cigarette reinforcement tended to be greater during abstinence for speeded accuracy but not the ERN. The effect of money reinforcement was unaffected by abstinence. CONCLUSIONS: The impact of smoking abstinence on reinforcement may depend on task demands. However, the effects of cigarette and money reinforcement generalize well from operant paradigms to cognitive tasks, fostering integration between the two literatures. Results provided modest evidence of abstinence-induced increases in smoking reinforcement; the absence of abstinence-induced reductions in nondrug reinforcement is consistent with recent work in suggesting that such effects are limited to a subset of sensory reinforcers. IMPLICATIONS: This study draws attention to the need for greater integration of reinforcement and cognition to better understand the mechanisms that contribute to smoking relapse. Results emphasize thoughtful consideration of the nature of the nondrug reinforcer(s) included in the study of smoking abstinence in addition to the levels of cognitive demand impacted by acute smoking abstinence.

Cognitive appraisals of alcohol use in early adolescence: Psychosocial predictors and reciprocal associations with alcohol use.

Early adolescence is a dynamic period for the development of alcohol appraisals (expected outcomes of drinking and subjective evaluations of expected outcomes), yet the literature provides a limited understanding of psychosocial factors that shape these appraisals during this period. This study took a comprehensive view of alcohol appraisals and considered positive and negative alcohol outcome expectancies, as well as subjective evaluations of expected outcomes. Developmental-ecological theory guided examination of individual, peer, family, and neighborhood predictors of cognitive appraisals of alcohol and use. A community sample of 378 adolescents (mean age 11.5 years at Wave 1, 52% female) was assessed annually for 4 years. Longitudinal path analysis suggested that the most robust predictors of alcohol appraisals were peer norms. Furthermore, perceived likelihood of positive and negative alcohol outcomes prospectively predicted increases in drinking. There was limited support for appraisals operating as mediators of psychosocial risk and protective factors.

The Nicotine Metabolite Ratio is Associated With Early Smoking Abstinence Even After Controlling for Factors That Influence the Nicotine Metabolite Ratio.

INTRODUCTION: The decrease in smoking rates in North America has plateaued, underscoring the need for new approaches to treat nicotine dependence. Inter-individual differences in smoking behavior result, in part, from variation in the rate of CYP2A6-mediated nicotine metabolism. A phenotypic measure of CYP2A6 activity is the nicotine metabolite ratio (NMR), the ratio of 3'hydroxycotinine/cotinine. The NMR is associated with smoking cessation. However, the NMR is also associated with genetic (eg, CYP2A6 genotype) and other (eg, sex and ethnicity) factors. Here we aimed to determine if previously identified non-CYP2A6 sources of variation in the NMR mitigated the association between the NMR and short-term abstinence. METHODS: The NMR was determined from blood samples collected at intake from daily smokers aged 18-65. Biochemically-verified point prevalence abstinence (exhaled carbon monoxide level ≤ 8 ppm) was measured at 1 week following the target quit date in participants from a smoking cessation clinical trial (NCT01314001). Analyses were restricted to N = 462 blacks and N = 693 whites in the intent-to-treat sample. RESULTS: Lower NMR (<0.31) was associated with a higher likelihood of 1-week abstinence (OR = 1.43; 95% CI = 1.12, 1.84). NMR was associated with abstinence even after controlling for treatment arm (nicotine patch or varenicline) and factors previously associated with NMR variation including sex, ethnicity, estrogen-containing hormonal therapy, body mass index, alcohol, and cigarette consumption. CONCLUSIONS: NMR was associated with 1-week smoking abstinence; NMR may be a useful addition to medication screening approaches evaluating treatments for nicotine dependence.

Does cannabis use moderate smoking cessation outcomes in treatment-seeking tobacco smokers? Analysis from a large multi-center trial.

BACKGROUND AND OBJECTIVE: Tobacco and cannabis are frequently used in combination and cannabis co-use may lead to poor tobacco cessation outcomes. Therefore, it is important to explore if cannabis co-use is associated with a reduced likelihood of achieving successful tobacco abstinence among treatment-seeking tobacco smokers. The present study examined whether current cannabis use moderated tobacco cessation outcomes after 12 weeks of pharmacological treatment (varenicline vs. nicotine patch vs. placebo) with adjunctive behavioral counseling. METHODS: Treatment-seeking tobacco smokers (N = 1,246) were enrolled in an intent-to-treat study, of which 220 were current cannabis users. Individuals were randomly assigned to 12 weeks of placebo (placebo pill plus placebo patch), nicotine patch (active patch plus placebo pill), or varenicline (active pill plus placebo patch), plus behavioral counseling. The primary endpoint was biochemically verified 7-day point prevalence abstinence at the end of treatment. RESULTS: Controlling for rate of nicotine metabolism, treatment arm, age, sex, alcohol, and level of nicotine dependence, cannabis users were as successful at achieving biochemically verified 7-day point prevalence abstinence compared to tobacco-only smokers. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Findings suggest that cannabis use does not hinder the ability to quit tobacco smoking. Future tobacco cessation studies should employ prospective, longitudinal designs investigating cannabis co-use over time and at different severity levels. (Am J Addict 2016;25:291-296).

Evaluating cognitive and motivational accounts of greater reinforcement effects among children with attention-deficit/hyperactivity disorder.

BACKGROUND: Attention Deficit/Hyperactivity Disorder is associated with cognitive deficits and dysregulated motivation. Reinforcement improves cognitive performance, often to a greater degree among children with ADHD compared to typically-developing controls. The current study tests the degree to which cognitive (individual differences in baseline cognition) and/or motivational (individual differences in Sensitivity to Reward; SR) processes can account for diagnostic group differences in reinforcement effects. METHODS: Participants were 58 children (25 ADHD, 33 control) ages 9-12. Children completed measures of inhibitory control (Stop Signal Task), working memory (n-back), and sustained attention (Continuous Performance Task) during a baseline week and again one week later under reinforcement and no-reinforcement conditions; composites were computed across cognitive domains. Parent-and child-reported trait SR (SPSRQ; BIS/BAS) were combined to index a child's response towards appetitive, rewarding stimuli. RESULTS: In separate analyses, diagnostic group, individual differences in baseline cognition, and individual differences in SR all moderated the impact of reinforcement on cognition. When considered together, the Diagnostic Group × Reinforcement and Baseline Cognition × Reinforcement interactions both remained robust. In contrast, neither the Diagnostic Group × Reinforcement nor the SR × Reinforcement interactions accounted for unique variance when evaluated together. CONCLUSIONS: Both baseline cognition and trait SR predict reinforcement effects on cognition, but only SR shares significant variance with diagnostic group. These results suggest that ADHD children's greater response to reinforcement on cognition is strongly related to their heightened trait sensitivity to rewarding stimuli, consistent with motivational models of ADHD.

The moderating role of cognitive capacities in the association between social norms and drinking behaviors.

BACKGROUND: The literature documents 2 related yet distinct social normative influences on adolescent drinking. Descriptive norms refer to perceptions of how much others engage in a particular behavior, whereas injunctive norms refer to the extent to which others approve of a particular behavior. Theoretical formulations suggest that whether descriptive or injunctive norms guide drinking behavior depends on cognitive factors related to executive functioning. Cognitive capacities, specifically inhibitory control (IC) and preplanning, were tested as moderators of the association between social norms and alcohol use using a longitudinal design and community sample of adolescents. METHODS: This longitudinal study included 387 adolescents and 3 annual waves of data. Behavioral tasks assessed IC (Stop Signal Task) and preplanning (Tower of London) and social norms and drinking were assessed using self-report measures. RESULTS: Significant interactions were found for descriptive and injunctive norms with preplanning and descriptive norms with IC. As hypothesized, descriptive norms were stronger prospective predictors of alcohol use at low levels of cognitive preplanning, whereas injunctive norms were stronger prospective predictors at high levels of cognitive preplanning. Descriptive norms prospectively predicted alcohol use at high, but not at low levels of IC. CONCLUSIONS: These findings highlight the complexity of normative influences and suggest that descriptive and injunctive norms have differential effects on future drinking for individuals with different cognitive capacities.