Effects of Ovarian Hormone Levels on Stress, Cigarette Craving, and Smoking in a Laboratory Relapse Paradigm Among Females Who Smoke Daily.

INTRODUCTION: Females, versus males, have shown a slower decline in smoking prevalence, greater smoking-related mortality and morbidity, and tend to have more difficulty achieving and maintaining abstinence. Identifying sex-specific risk factors is needed to improve outcomes. Though ovarian hormones have been evaluated for their role in smoking and relapse, measures tend to be static and infrequent, failing to capture the influence of increasing or decreasing levels. AIMS AND METHODS: The present study evaluated the effect of static and fluctuating levels of ovarian hormones (ie, progesterone, estradiol, and estrogen to progesterone [E/P] ratio) on stress reactivity, cigarette craving, and smoking during a laboratory relapse paradigm. Female participants (assigned female at birth) reporting daily cigarette smoking (N = 91, ages 18-45) were recruited from the community. Participants provided daily salivary ovarian hormone levels leading up to a laboratory session, in which stress was induced and stress reactivity, cigarette craving, latency to smoke, and ad-libitum smoking were measured. RESULTS: Static levels of estradiol were associated with stress reactivity (ß = 0.28, SE = 0.13) and static E/P ratio was associated with smoking in the laboratory (HR = 1.4). Preceding 3-day changes in estradiol and E/P ratio, but neither static levels nor preceding 3-day changes in progesterone were associated with stress reactivity, cigarette craving, or smoking in a relapse paradigm. CONCLUSIONS: Ovarian hormones are among several sex-specific factors involved in the complex neuroendocrine response to stress, and their interaction with other biological, social, and psychological factors in the real-world environment is not yet fully understood. IMPLICATIONS: Findings of the present study provide novel information regarding the role of ovarian hormones among female participants who smoke daily in stress reactivity and smoking in the context of a laboratory relapse paradigm and highlight several avenues for future research. We found that same-day estradiol levels were associated with increased subjective stress reactivity and same-day estrogen to progesterone ratio was associated with increased likelihood of smoking in a relapse paradigm. Ovarian hormones are among several sex-specific factors contributing to the complex neuroendocrine response to stress, and their interaction with other biological, social, and psychological factors in the real-world environment is not yet fully understood.

The Role of Emotion Differentiation in the Association Between Momentary Affect and Tobacco/Nicotine Craving in Young Adults.

INTRODUCTION: Tobacco/nicotine use is commonly initiated during adolescence or young adulthood, which increases the likelihood of continued use into adulthood and related adverse health outcomes. Despite interest in cessation, achieving and maintaining abstinence is difficult among this population. Cravings are often a barrier to abstinence, which have been associated with intensity of affect at the moment level. Emotion differentiation involves the ability to distinguish between discrete emotion states, and previous work suggests it may moderate the effect of momentary affect on craving, which has never been explored among young adults who are smoking or vaping nicotine. AIMS AND METHODS: In a sample of young adults (N = 37, observations = 2020, ages 18-25, 51% female, and 78% white) interested in quitting smoking or vaping, we used real-time, naturalistic data capture via mobile phones to examine the interaction of momentary affect and trait emotion differentiation on nicotine craving. Participants were prompted with four surveys per day for 35 days and asked to make a 48-h quit attempt on day 7. RESULTS: Multilevel models showed moments of higher-than-average momentary negative affect (NA; b = 0.39, p < .001), and positive affect (PA; b = 0.26, p = .001) were associated with greater levels of craving. NA emotion differentiation significantly moderated the associations between PA and craving (b = -0.63, p = .031) and NA and craving (b = -0.67, p = .003). CONCLUSIONS: Findings from this exploratory analysis suggest that for young adults engaging in a nicotine quit attempt, greater ability to differentiate NA weakens the momentary association between intense affect and craving. IMPLICATIONS: Results of this study show that the ability to differentiate between discrete emotional experiences may protect young adults against nicotine craving during moments of intense affective experience. These preliminary findings suggest that emotion differentiation, a modifiable construct, could be an important treatment target for individuals engaged in treatment for nicotine dependence.

Differential prevalence of Adverse Childhood Experiences (ACEs) by gender and substance used in individuals with cannabis, cocaine, opioid, and tobacco use disorders.

Background: Adverse childhood experiences (ACEs) show a graded association with the development of substance use disorders (SUDs) and engagement in risky substance use behaviors. Women are overrepresented among individuals with more severe childhood adversity (≥4 types of ACEs) and may be at particular risk for aberrant substance use.Objectives: To assess the prevalence of ACEs among men and women with cannabis, opioid, cocaine, and tobacco use disorders.Methods: Non-treatment-seeking individuals participating in clinical addiction research at a single site completed the ACE questionnaire and provided a detailed substance use history. Data were analyzed using proportional odds models and logistic regression.Results: Most participants (424/565; 75%) reported at least one ACE, and more than one-quarter (156/565; 27%) reported severe childhood adversity. Relative to men (n = 283), women (n = 282) reported more ACEs (OR = 1.49; p = .01) and more experiences of emotional/physical abuse (OR = 1.52; p = .02), sexual abuse (OR = 4.08; p = .04), and neglect (OR = 2.30; p < .01). Participants in the cocaine (OR = 1.87; n = .01) and opioid (OR = 2.21; p = .01) use disorder, but not cannabis use disorder (OR = 1.46; p = .08), studies reported more severe adversity relative to the tobacco group. Relative to tobacco users, emotional/physical abuse (OR = 1.92; p = .02) and neglect (OR = 2.46; p = .01) scores were higher in cocaine users and household dysfunction scores were higher in opioid users (OR = 2.67; p = .01).Conclusion: The prevalence of ACEs differs with respect to both participant gender and primary substance used. Novel SUD treatment strategies that incorporate ACEs may be uniquely beneficial in specific subpopulations of people with SUDs.

Characterization of Salivary Progesterone in Female Smokers.

INTRODUCTION: Fluctuations in ovarian hormones have been associated with changes in cigarette smoking behavior, which can be measured through both serum or less invasive salivary procedures. The primary aim of this exploratory study is to characterize the progesterone profiles of salivary progesterone measurements and to compare that with the profiles estimated from a previously measured serum sample. AIMS AND METHODS: Nontreatment-seeking, cigarette smoking women (n = 82; ages 18-45 years) provided daily salivary hormone samples every morning for 14 consecutive days. Time-dependent random effects functions were used to approximate daily salivary progesterone (ng/mL) levels over the course of a standardized menstrual cycle. Serum measures of progesterone from a previous study of female cigarette smokers were examined for consistency with established profiles and compared with the salivary profile using the same methodology. RESULTS: The salivary model fit exhibits relative stability during the follicular phase and a clear unimodal peak during the luteal phase. Parameter estimates from the non-linear function show correspondence to serum data. Although the profiles estimated from salivary and serum data agree in functional form, we observed larger between-subject heterogeneity both in the follicular level and the peak luteal level in salivary measures. CONCLUSIONS: The pattern of salivary and serum progesterone measured across the menstrual cycle is similar in form, which is noteworthy given that the saliva and serum samples were drawn from independent sample of female smokers. Inter- and intra-individual variation in salivary measures may be greater than in serum measures. IMPLICATIONS: Measuring progesterone level variation across the menstrual cycle via saliva samples has several benefits relative to serum sampling methods in that they are easily obtained, noninvasive, and low-cost. Inter- and intra-individual variation in measurements may be greater than those in serum measurements. However, the functional form of the salivary progesterone profile is isomorphic to serum progesterone.

Assessment of patient perception of treatment assignment and patient-reported outcomes in a cannabis use disorder trial.

Background: Blinding is a cornerstone of trial methodology. Prior work indicates participant-perceived assignment may be associated with trial outcomes. Less is known about how perception changes over time and if this is associated with outcomes.Objectives: To evaluate if participants change their perception of assignment over time in a blinded trial, and if perception is associated with different types of patient-reported outcomes (PROs).Methods: This was a secondary analysis of data from the Achieving Cannabis Cessation-Evaluating N-Acetylcysteine Treatment (ACCENT) trial, which evaluated the efficacy of N-acetylcysteine (NAC) relative to placebo for treating cannabis use disorder. Participants (N = 234; 164 men, 70 women) were asked at weeks 5 and 9 what treatment (placebo or NAC) they believed they were receiving. We included PROs proximal (cannabis-associated problems, craving) and distal (anxiety) to the intervention. Analysis was by multiple linear regression and mixed models.Results: Approximately 20% of participants in both arms changed their perception over time. Relative to participants who consistently perceived assignment to placebo, participants who consistently perceived assignment to NAC did not always have comparatively better average scores (coefficient -3.3 [95% CI: -7.0, 0.5]). In some analyses, participants who switched to guessing NAC from placebo had comparatively better average scores (coefficient -3.0 [95% CI: -9.3, 3.4]), but this was inconsistent across outcomes or strata defined by actual assignment or guess accuracy.Conclusion: The study suggests that the proportion of individuals who switch their perception over time is modest. However, this group may influence the estimates of intervention effects on some PROs.

A Pilot Randomized Clinical Trial of Remote Varenicline Sampling to Promote Treatment Engagement and Smoking Cessation.

INTRODUCTION: Medication sampling is a clinically useful tool to engage smokers in the quitting process. Whether varenicline is suitable for sampling purposes is unclear. The purpose of this study was to examine the feasibility, uptake, and preliminary outcomes of varenicline sampling. METHODS: Smokers (N = 99), both motivated to quit and not, were recruited and randomized to varenicline sampling versus not, with 12 week follow-up. The intervention consisted of mailing one-time samples of varenicline (lasting 2-4 wks), with minimally suggestive guidance on use. RESULTS: Uptake of varenicline was strong, at 2 weeks (54% any use, 66% daily use) and 4 weeks (38%, 46%), with 58% of medication users seeking additional medication. Most users followed conventional titration patterns, self-titrating from 0.5 mg to 2 mg. Relative to control, varenicline sampling increased motivation (p = 0.006) and confidence to quit (p = 0.02), and decreased cigarette smoking (p = 0.02). Smokers receiving varenicline samples were significantly more likely to achieve 50% reduction in cigarettes per day (CPD), both immediately following the sampling exercise (Adjusted Odds Ratio [AOR] = 4.12; 95% CI: 1.39 to 12.17) and at final follow-up (AOR = 4.50; 95% CI: 1.56 to 13.01). Though cessation outcomes were not statistically significant, there was a 1.5 to 3-fold increase in quit attempts and abstinence from varenicline sampling throughout follow-up. These outcomes were comparable among smokers motivated to quit and not. CONCLUSIONS: Unguided, user-driven sampling of varenicline sampling is a concrete behavioral exercise that is feasible to do and seems to suggest clinical utility. Sampling is a pragmatic clinical approach to engage more smokers in quitting. IMPLICATIONS: Use of evidence-based pharmacotherapies for smoking cessation is low. Medication sampling is a pragmatic behavioral exercise that allows smokers to experience the benefits of using them, while promoting positive downstream effects towards quitting. While previous studies have shown that nicotine replacement therapy (NRT) sampling is viable and effective, whether this extends to varenicline is unclear. Results from this trial demonstrate that varenicline sampling is feasible, safe, and suggestive of clinically important steps toward quitting, deserving of a larger trial. CLINICAL TRIAL REGISTRATION: NCT #03742154.

Increases in endogenous progesterone attenuate smoking in a cohort of nontreatment seeking women: An exploratory prospective study.

Despite advances in prevention and treatment, cigarette smoking remains a leading cause of preventable death in the United States. Although men and women are equally likely to attempt to quit smoking cigarettes, women are far less likely to achieve abstinence both during and following cessation treatment. Recent evidence suggests that ovarian hormone levels may play a role in successful abstinence attempts in women smokers. The primary goal of this exploratory prospective observational study was to estimate the association between within-participant levels of progesterone and estradiol with associated cigarettes smoked per day in adult women smokers (n = 104). The primary study outcome was self-reported cigarettes smoked per day (CPD) during a 2-week observational period collected using a daily smoking diary. Additionally, participants collected saliva daily, from which hormone levels (progesterone and estradiol) were derived. Higher within-participant progesterone levels were associated with a significant decrease in CPD (p = .008) whereas within-participant estradiol levels were unrelated to CPD (p = .25). Regression models indicated a single change in the trajectory of smoking behavior for both within-participant progesterone and estradiol. When progesterone values were below the change point, there was a significant inverse relationship between within-participant progesterone levels and smoking behavior (p = .025) whereas the relationship was attenuated for higher within-participant progesterone levels (p = .59). The effect of estradiol on smoking behavior was not significant when it was either below (p = .92) or above (p = .16) the change point. Higher within-participant levels of progesterone but not estradiol are associated with reduced CPD in nontreatment seeking women smokers.

The estimand framework and its application in substance use disorder clinical trials: a case study.

Relapse rates among individuals with substance use disorder (SUD) remain high and new treatment approaches are needed, which require evaluation in randomized controlled trials (RCTs). Measurement and interpretation challenges for SUD RCT data are often ignored or presented only in statistical analysis plans. Since different analytic approaches may result in different estimates and thus interpretations of the treatment effect, it is important to present this clearly throughout the trial. Inconsistencies between study analyses and objectives present further challenges for interpretation and cross-study comparisons. The recent International Council for Harmonization (ICH) addendum provides standardized language and a common framework for aligning trial objectives, design, conduct, and analysis. The framework focuses on estimands, which describe the treatment effect and link the trial objective with the scientific question and the analytic approach. The use of estimands offers SUD researchers and clinicians the opportunity to explicitly address events that affect measurement and interpretation at the outset of the trial. Furthermore, the use of standard terminology can lead to clearer interpretations of SUD trials and the treatments evaluated in SUD trials. Resources for understanding and applying estimands are needed to optimize the use of this new, helpful framework. This Perspective provides this resource for SUD researchers. Specifically, it highlights the relevance of estimands for SUD trials. Furthermore, it demonstrates how estimands can be used to develop clinically relevant analyses to address challenges in SUD trials. It also shows how a standardized framework can be employed to improve the interpretation and presentation of SUD study findings.

Cannabis and Alcohol Co-Use in a Smoking Cessation Pharmacotherapy Trial for Adolescents and Emerging Adults.

INTRODUCTION: The co-use of cannabis and alcohol among tobacco-using youth is common. Alcohol co-use is associated with worse tobacco cessation outcomes, but results are mixed regarding the impact of cannabis on tobacco outcomes and if co-use leads to increased use of non-treated substances. This secondary analysis from a youth smoking cessation trial aimed to (1) evaluate the impact of cannabis or alcohol co-use on smoking cessation, (2) examine changes in co-use during the trial, and (3) explore secondary effects of varenicline on co-use. METHODS: The parent study was a 12-week, randomized clinical trial of varenicline for smoking cessation among youth (ages 14-21, N = 157; Mage = 19, 40% female; 76% White). Daily cigarette, cannabis, and alcohol use data were collected via daily diaries during treatment and Timeline Follow-back for 14 weeks post-treatment. RESULTS: Baseline cannabis co-users (68%) had double the odds of continued cigarette smoking throughout the trial compared with noncannabis users, which was pronounced in males and frequent cannabis users. Continued smoking during treatment was associated with higher probability of concurrent cannabis use. Baseline alcohol co-users (80%) did not have worse smoking outcomes compared with nonalcohol users, but continued smoking was associated with higher probability of concurrent drinking. Varenicline did not affect co-use. CONCLUSIONS: Inconsistent with prior literature, results showed that alcohol co-users did not differ in smoking cessation, whereas cannabis co-users had poorer cessation outcomes. Youth tobacco treatment would benefit from added focus on substance co-use, particularly cannabis, but may need to be tailored appropriately to promote cessation. IMPLICATIONS: Among youth cigarette smokers enrolled in a pharmacotherapy evaluation clinical trial, alcohol and/or cannabis co-use was prevalent. The co-use of cannabis affected smoking cessation outcomes, but more so for males and frequent cannabis users, whereas alcohol co-use did not affect smoking cessation. Reductions in smoking were accompanied by concurrent reductions in alcohol or cannabis use. Substance co-use does not appear to affect all youth smokers in the same manner and treatment strategies may need to be tailored appropriately for those with lower odds of smoking cessation.

Sex Differences in Subjective and Behavioral Responses to Stressful and Smoking Cues Presented in the Natural Environment of Smokers.

INTRODUCTION: Some evidence suggests that female smokers may show more context-dependent smoking and that males may show more stereotyped smoking (regardless of stress or cue exposure). The goal of this study was to characterize sex differences in response to stressful and smoking cues ecologically presented in daily life and variability in day-to-day smoking behavior. METHODS: Adult smokers (N = 177) provided ratings of mood and cigarette craving before and after stress and smoking cues were presented four times daily for 14 days via a mobile device. Linear mixed models tested whether (1) female smokers exhibited greater reactivity to stressful cues than male smokers; (2) pre-cue negative affect increased reactivity to smoking cues more in female smokers than male smokers; (3) across both sexes, greater reactivity to stressful and smoking cues correlated with greater quantity of smoking within a day; and (4) female smokers exhibited greater variability in cigarettes per day (CPD) relative to males. RESULTS: Relative to male smokers, female smokers reported greater negative affect, stress, and craving in response to stressful cues, but not smoking cues, after accounting for time since last cigarette and pre-cue responding. No sex differences in CPD or variability in CPD were detected. Days with higher subjective reactivity to cues were not associated with increased smoking, in either males or females. CONCLUSIONS: Sex differences were observed in response to stress but not smoking cues in the natural environment of regular cigarette smokers. Further research is necessary to evaluate whether stress reactivity in female smokers is associated with reduced latency to smoke following stress exposure in daily life. IMPLICATIONS: This study provides naturalistic evidence that female smokers may not be more reactive to smoking cues than males, but experience heightened stress and craving following stress exposure. There was no evidence to support the hypothesis that amount smoked per day varied more for females, relative to males, as a result of more context-driven smoking for females.

Association of Cannabis Use With Intimate Partner Violence Among Couples With Substance Misuse.

BACKGROUND AND OBJECTIVES: There is a well-established causal link between substance use and intimate partner violence (IPV) perpetration and victimization. However, little is known about the complex emerging relationship between cannabis use and IPV. Because cannabis is the most commonly used drug in the United States and is associated with numerous IPV risk factors such as alcohol use, it is important to examine this relationship in greater detail. METHOD: The current exploratory study examined the association between (a) self-reported cannabis use during the past 90 days and (b) Δ9-tetrahydrocannabinol (THC) urine drug screens and IPV perpetration and victimization in a sample of 30 alcohol or drug-misusing community couples (N = 60 individual participants). RESULTS: The majority of participants (n = 50 individuals, 83.3%) had concordant cannabis self-reported and urine drug screen results. After accounting for demographic variables and quantity and frequency of alcohol and stimulant use, greater quantity and frequency of cannabis use as well as positive THC urine drug screen results were associated with greater physical IPV victimization, and greater quantity and frequency of cannabis were associated with greater IPV psychological victimization and perpetration, and physical IPV victimization. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Findings emphasize the unique and important role that cannabis plays in the occurrence of IPV among intact couples. Findings also underscore the feasibility and utility of integrating confirmatory biological samples into future studies on this topic in order to advance the science in this area. (Am J Addict 2020;00:00-00).

Image processing and analysis methods for the Adolescent Brain Cognitive Development Study.

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data is a resource of unprecedented scale and depth for studying typical and atypical development. The aim of this manuscript is to describe the baseline neuroimaging processing and subject-level analysis methods used by ABCD. Processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI. This manuscript serves as a methodological reference for users of publicly shared neuroimaging data from the ABCD Study.

Adolescent Substance Use Disorder Treatment: an Update on Evidence-Based Strategies.

PURPOSE OF REVIEW: To examine the most recent published evidence (2016-2019) regarding the treatment of adolescent substance use disorders and to provide an update on evidence-based strategies, adjunctive interventions, and methods to improve currently established treatment approaches. RECENT FINDINGS: Recent evidence suggests that psychosocial treatments such as family-based therapy, cognitive behavioral therapy, and multicomponent approaches remain the most effective methods of treatment; however, innovative ways of improving these treatment strategies may include digital and culturally based interventions. New advances in adjunctive treatments such as pharmacotherapy, exercise, mindfulness, and recovery-oriented educational centers may have some clinical utility. Well-established psychosocial interventions remain the primary modality of treatment. Promising new adjunctive treatments and improvements in our currently established treatments may yield significant improvements.

Using REDCap for ambulatory assessment: Implementation in a clinical trial for smoking cessation to augment in-person data collection.

BACKGROUND: The use of ambulatory assessment to study behavior and physiology in daily life is becoming more common, yet barriers to implementation remain. Limitations in budget, time, and expertise may inhibit development or purchase of dedicated ambulatory assessment software. Research Electronic Data Capture (REDCap) is widely used worldwide, offering a cost-effective and accessible option for implementing research studies. OBJECTIVES: To present a step-by-step guideline on how to implement ambulatory assessment using REDCap and provide preliminary evidence of feasibility. METHODS: Feasibility and acceptability data are presented for randomized participants (N ranged from 19 to 36, depending on analysis) from an ongoing 8-week smoking cessation pharmacological clinical trial (ClinicalTrials.gov Identifier: NCT02737358). Participants (N = 36; 50% female) completed up to three ambulatory assessment surveys per day, depending on the phase of the study. These included self-report and video confirmation of smoking biomarkers and medication adherence. RESULTS: Participants completed 74.8% of morning reports (86.6% for study completers), 73.8% of videos confirming smoking biomarkers, and 70.4% of videos confirming medication adherence. Study completers reported that the REDCap assessments were easy to use, and 78.9% of participants preferred the REDCap assessments to traditional, paper measures. CONCLUSIONS: These data from a pharmacological trial suggest feasibility of remote data collection using REDCap. As REDCap functionality is continually evolving, it is likely that options for collecting ambulatory assessment data via this platform will progressively improve allowing for greater individualization of assessment scheduling for enhancing data collection in clinical trials.

Research Review: What have we learned about adolescent substance use?

BACKGROUND: Adolescence is a critical biological, psychological, and social developmental stage involving heightened risk for substance use and associated adverse consequences. This review, synthesizing emerging findings on this complex topic, is intended to inform research and clinical care focused on adolescents. METHODS: Literature searches were conducted using PubMed, yielding a cross-section of observational and interventional studies focused on adolescent substance use. Findings were organized and categorized to cover key areas of epidemiology, neurobiology, prevention, and treatment. FINDINGS: Adolescent substance-related attitudes and use patterns have evolved over time, informed by adult and peer behaviors, public policy, media messaging, substance availability, and other variables. A number of risk and resiliency factors contribute to individual differences in substance use and related consequences. Advances in observational techniques have provided enhanced understanding of adolescent brain development and its implications for substance use. Prevention efforts have yielded mixed results, and while a number of adolescent-targeted evidence-based treatments for substance use disorders have been developed, effect sizes are generally modest, indicating the need for further research to enhance prevention and treatment outcomes. CONCLUSIONS: Substance use in adolescence is heterogeneous, ranging from normative to pathological, and can lead to significant acute and long-term morbidity and mortality. Understanding risk and resiliency factors, underlying neurobiology, and optimal developmentally sensitive interventions is critical in addressing substance-associated problems in adolescence.

Impact of cannabis legalization on treatment and research priorities for cannabis use disorder.

An increasing proportion of the world has legalized cannabis for medicinal or recreational use. The legalization trend appears to be continuing. These changes in the legislative landscape may have important health, treatment, and research implications. This review discusses public health outcomes that may be impacted by increases in cannabis availability and use. It additionally considers potential research and treatment priorities in the face of widespread cannabis legalization.

Acceptability and compliance with a remote monitoring system to track smoking and abstinence among young smokers.

BACKGROUND: Similar to adult smokers, quit attempts among younger smokers almost inevitably result in relapse. Unlike adults, less is known about the process of relapse in this younger age group. A technology-based remote monitoring system may allow for detailed and accurate characterization of smoking and abstinence and would help to improve cessation strategies. OBJECTIVES: This study describes a mobile system that captures smoking using breath carbon monoxide (CO) and real-time self-reports of smoking behavior. Compliance, feasibility, acceptability, and accuracy of the system were measured during a quit attempt and subsequent monitoring period. METHODS: The mobile application (My Mobile Monitor, M3) combined breath CO with ecological momentary assessment, delivered via smartphone. Participants (N = 16; 75% female) were daily smokers between the ages of 19 and 25, who used the app for 11 days during which they agreed to make a quit attempt. Acceptability, compliance, and abstinence were measured. RESULTS: Participants averaged 22.3 ± 2.0 years old and smoked an average of 13.0 ± 6.1 cigarettes per day. Overall session compliance was 69% and during the quit attempt, 56% of participants abstained from smoking for at least 24 hours. Agreement between self-reported smoking compared to breath CO was generally high, when available for comparison, though underreporting of cigarettes was likely. CONCLUSION: This study demonstrates feasibility of a remote monitoring app with younger smokers, though improvements to promote compliance are needed. Remote monitoring to detect smoking and abstinence represents a step forward in the improvement of cessation strategies, but user experience and personalization are vital.

Perceptions of Snus Among US Adult Smokers Given Free Product.

INTRODUCTION: Snus uptake is nominal among US smokers. This longitudinal study examines (1) perceptions of snus among US smokers given free snus for 6 weeks and (2) a method for assessment of an alternative tobacco product at the population level. METHODS: Adult smokers (n = 543; 69.2% female; Mage = 49.3 years), uninterested in quitting, received free snus for ad libitum use. Based on their snus use during a 6-week sampling period, participants included: (1) never users (18.4%, n = 100); (2) experimenters; that is, used ≥ once, but not during the last week of sampling (33.1%; n = 180); and (3) persistent users; that is, used ≥ once during the final week, and ≥ once during any other week of the sampling period. (48.4%; n = 263). RESULTS: Following the sampling period, those who became persistent users were more likely than experimenters to report that switching to alternative tobacco products would lower their risk for health problems (66.5% vs. 50.0%; p = .006). Persistent users also reported greater negative affect relief and craving reduction (ps < .001) than experimenters. Finally, persistent users were more likely than experimenters to describe snus in favorable terms with respect to ease of use, satisfaction, and liking (ps < .05). CONCLUSIONS: Subjective experiences with snus, rather than nicotine dependence, explained experimentation versus persistent use. Even among smokers who became persistent snus users, snus was perceived as a poor substitute for cigarettes. This study design (randomized, yet naturalistic) could be extended to other novel tobacco products, including e-cigarettes, to help understand the role new products may have in the tobacco landscape. IMPLICATIONS: This is the first large scale, US-based naturalistic assessment of smokers' reactions to snus during an extended sampling period. This study is directly in line with FDA goals to better understand predictors of initiation, uptake, and use of other tobacco products such as snus, and serves as model for assessment methods of alternative tobacco products at the population level. Most smokers tried the provided sample of snus (approximately 82%). Subjective experiences with snus, rather than nicotine dependence, explained experimentation versus persistent use. Even among smokers who became persistent snus users, snus was perceived as a poor substitute for cigarettes.

Snus undermines quit attempts but not abstinence: a randomised clinical trial among US smokers.

BACKGROUND: Observational studies and a few clinical trials suggest that use of low nitrosamine smokeless tobacco (snus) can facilitate smoking cessation. To better understand the real-world impact of snus on smoking behaviour, a large-scale, long-term clinical trial of naturalistic snus use among smokers is needed. STUDY DESIGN: A nationwide clinical trial compared abstinence outcomes among smokers who were randomised to receive free samples of snus versus not. Participants (N=1236) were recruited throughout the US and assessed for 1 year following a 6-week naturalistic sampling period, with high retention throughout. Primary outcomes included self-reported quit attempts, floating abstinence (any 7-day period of non-smoking) and 7-day point-prevalence abstinence at 6 months and 12 months. Secondary outcomes were changes in smoking, motivation and confidence to quit and adverse events. No tobacco industry support was provided. RESULTS: Within snus group, 82% used at least once, and 16% were using regularly at end of sampling period. Compared to control participants, smokers in the snus group were less likely to make any quit attempt (RR=0.83; 95% CI 0.70 to 1.00), and any 24 h quit attempt (RR=0.77; 95% CI 0.63 to 0.95). There were no group differences on any measure of abstinence. CONCLUSIONS: Provision of snus in a naturalistic context resulted in minimal uptake, and as a whole, undermined quit attempts and did not increase smoking abstinence. Results do not support the unguided, free provision of snus among smokers not motivated to quit as a means to facilitate quit attempts. TRIAL REGISTRATION NUMBER: NCT01509586, Results.

Neuroimaging the neural correlates of increased risk for substance use disorders in attention-deficit/hyperactivity disorder-A systematic review.

BACKGROUND/OBJECTIVES: Children with attention-deficit/hyperactivity disorder (ADHD) are nearly three times more likely to develop substance use disorders (SUD) than their typically developing peers. Our objective was to review the existing neuroimaging research on high-risk ADHD (ie, ADHD with disruptive behavior disorders, familial SUD and/or early substance use), focusing on impulsivity as one possible mechanism underlying SUD risk. METHODS: A PubMed literature search was conducted using combinations of the keywords "ADHD," "substance use," "substance use disorder," "SUD," "addiction," "dependence," "abuse," "risk," "brain" "MRI," "imaging" and "neuroimaging." Studies had to include cohorts that met diagnostic criteria for ADHD; studies of individuals with ADHD who all met criteria for SUD were excluded. Eight studies met the search criteria. RESULTS: Individuals with high-risk ADHD have hyperactivation in the motivation-reward processing brain network during tasks of impulsive choice, emotion processing, and risky decision-making. During response inhibition tasks, they have hypoactivation in the inhibitory control brain network. However, studies focusing on this latter circuit found hypoactivation during inhibitory control tasks, decreased white matter microstructure coherence and reduced cortical thickness in ADHD independent of substance use history. DISCUSSION/CONCLUSIONS: An exaggerated imbalance between the inhibitory control network and the motivation-reward processing network is theorized to distinguish individuals with high-risk ADHD. Preliminary findings suggest that an exaggerated aberrant reward processing network may be the driving neural correlate of increased SUD risk in ADHD. SCIENTIFIC SIGNIFICANCE: Neural biomarkers of increased SUD risk in ADHD could help clinicians identify which patients may benefit most from SUD prevention. Thus, more neuroimaging research on this vulnerable population is needed. (Am J Addict 2017;26:99-111).