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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.

Childhood trauma exposure, including witnessing or experiencing family violence, is associated with a variety of poor outcomes such as increased likelihood of psychopathology and high-risk behaviors across the lifespan. Early treatment may help to buffer these effects, but parents and youth display only moderate levels of agreement in reporting family violence, making it more difficult to identify children who have been exposed. Additionally, most studies on family violence reporting have focused primarily on small samples in specific high-risk populations, and little is known about the generalizability of these findings. Thus, the present study assessed concordance in family violence reporting and its correlates using the population-based, demographically diverse sample from the U.S. Adolescent Brain Cognitive Development (ABCD®) study. Participants were 10,532 children between 9 and 10 years old, and their parent or guardian, from 21 sites across the United States. Overall, 30% ( N = 3119) of the sample reported family violence and most of those reports ( N = 2629) had discordant violence reporting, meaning child- and parent-report did not correspond with each other. Multinomial logistic regression was used to assess the likelihood of participants belonging in one of the following groups: no violence reported, concordant violence reported, and discordant violence reported. Results indicated that Black or Non-Hispanic children, male children, and children with greater externalizing problems were more likely to report family violence, and parents with lower levels of education and income were more likely to report family violence. These findings likely reflect differences in distribution of risk factors among racial and ethnic minoritized individuals including increased parenting stress and decreased access to mental health treatment. Among those reporting violence, Hispanic children and children with less externalizing problems were more likely to be in the discordant group. Findings suggest that both parent and child reports are needed to assess violence and screen for appropriate services.

Introduction Adoption of rigorous standards for reporting treatment fidelity is essential for advancing discovery, validation, and implementation of behavioral treatments. Whereas the NIH Behavior Change Consortium (BCC) developed an assessment tool to assess the quality of reporting and monitoring of treatment fidelity across health behavior change interventions, it has not yet been applied specifically to treatment fidelity in behavioral tobacco treatment trials. Aims and Methods We conducted a scoping review of peer-reviewed, clinical trials of behavioral adult tobacco treatment interventions published in English between 2006 and 2018. Using the BCC treatment fidelity checklist, articles were coded for the presence or absence of various treatment fidelity strategies within each of 5 domains: Design, Training, Delivery, Receipt, and Enactment. Eligible articles (N = 755) were coded by two independent coders. Results The proportion of reporting strategies varied within the fidelity domains, ranging from 5.2% to 96.3% in Design, 1.9% to 24.9% in Training, 2.6% to 32.3% in Delivery, 5.2% to 44.3% in Receipt, and 6.7% to 43.2% in Enactment. The mean proportion of adherence to treatment fidelity strategies within each domain was: Design (68%), Training (14%), Delivery (15%), Receipt (16%), and Enactment (25%). Only 11 studies achieved ≥80% reporting across >1 fidelity domain. There was no evidence for improvement in fidelity reporting across the 13-year time frame from the initial BCC publication to the present. Conclusions These findings illustrate the lack of consistency in fidelity reporting in tobacco treatment trials and underscore the challenges faced in evaluating rigor and reproducibility, as well as interpretation and dissemination of findings. Recommendations are made for improving fidelity reporting in tobacco treatment trials. Implications The SRNT Treatment Research Network sponsored a scoping review to summarize the current state of reporting treatment fidelity and make recommendations for best practices in reporting fidelity in tobacco treatment trials. The review identified a lack of consistency in fidelity reporting, illustrating the challenges faced in evaluating rigor, and reproducibility, as well as interpretation and dissemination of findings.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development. This paper reports activation patterns for fMRI tasks assessing response inhibition, working memory and reward processing obtained at baseline in the longitudinal ABCD Study, providing a reference for research into adolescent brain development.

BACKGROUND: Despite efforts towards gender parity and some improvement over time, gender bias in peer review remains a pervasive issue. We examined gender representation and homophily in the peer review process for Drug and Alcohol Dependence (DAD). METHODS: We extracted data for papers submitted to DAD between 2004 and 2019, inclusive. Inferred gender was assigned to handling editors and reviewers using the NamSor gender inference Application Programming Interface (API). RESULTS: Men and women handling editors were approximately equally likely to invite women reviewers over time, with only a few exceptions. Over time, 47.1% of editors were women, and 42.6% of review invitations were sent to women. Men were largely consistent over time in their likelihood of accepting a review invitation, while the likelihood of women accepting a review invitation was more variable over time. Gender differences in rates of accepting a review invitation were minimal; however, as women approached half of all invited reviewers in recent years, there has been a greater trend for women, relative to men, to decline review invitations. Evidence of homophily on the part of reviewers accepting invitations was minimal, but in certain years, a tendency to accept review invitations at higher rates from editors of the same gender was observed. DISCUSSION: Given the benefits of diversity in scientific advancement, these results underline the importance of continuing efforts to increase gender diversity among editors and in reviewer pools, and the need for reviewers to be mindful of their own reviewing practices.

Introduction Newly available, smartphone-enabled carbon monoxide (CO) monitors are lower in cost than traditional stand-alone monitors and represent a marked advancement for smoking research. New products are promising, but data are needed to compare breath CO readings between smartphone-enabled and stand-alone monitors. The purpose of this study was to (1) determine the agreement between the mobile iCO (Bedfont Scientific Ltd) with two other monitors from the same manufacturer (Micro+ pro and Micro+ basic) and (2) determine optimal, monitor-specific, cotinine-confirmed abstinence cutoff values. Methods Adult (≥18) smokers (n = 26) and nonsmokers (n = 21) provided three breath CO samples (using three different monitors) in each of 10 sessions, and urine cotinine was measured for gold standard determination of abstinence. CO comparisons (N = 437) were analyzed using regression-based Bland–Altman Analysis of Agreement; receiver operating characteristics curves were used to determine optimal abstinence cutoffs. Results Bland–Altman analyses indicated that the iCO monitor provided higher CO results than both Micro+ monitors. Sensitivity and specificity analyses showed that the optimal CO cutoff for determining abstinence was Conclusions Relative to both Micro+ monitors, the smartphone-enabled iCO provided systematically higher CO values and required a higher cutoff to reliably determine smoking abstinence. This does not indicate that CO values obtained using the iCO are not valid; instead, these results suggest that monitor-specific abstinence cutoffs are needed to ensure accurate bioverification of smoking status. Implications Results from this study indicate that CO values from the smartphone-enabled iCO should not be used interchangeably with the stand-alone Micro+ pro and Micro+ basic, particularly when lower CO values (

Most tobacco-focused clinical trials are based on locally conducted studies that face significant challenges to implementation and successful execution. These challenges include the need for large, diverse, yet still representative study samples. This often means a protracted, costly, and inefficient recruitment process. Multisite clinical trials can overcome some of these hurdles but incur their own unique challenges. With recent advances in mobile health and digital technologies, there is now a promising alternative: Remote Trials. These trials are led and coordinated by a local investigative team, but are based remotely, within a given community, state, or even nation. The remote approach affords many of the benefits of multisite trials (more efficient recruitment of larger study samples) without the same barriers (cost, multisite management, and regulatory hurdles). The Coronavirus Disease 2019 (COVID-19) global health pandemic has resulted in rapid requirements to shift ongoing clinical trials to remote delivery and assessment platforms, making methods for the conduct of remote trials even more timely. The purpose of the present review is to provide an overview of available methods for the conduct of remote tobacco-focused clinical trials as well as illustrative examples of how these methods have been implemented across recently completed and ongoing tobacco studies. We focus on key aspects of the clinical trial pipeline including remote: (1) study recruitment and screening, (2) informed consent, (3) assessment, (4) biomarker collection, and (5) medication adherence monitoring. Implications With recent advances in mobile health and digital technologies, remote trials now offer a promising alternative to traditional in-person clinical trials. Remote trials afford expedient recruitment of large, demographically representative study samples, without undo burden to a research team. The present review provides an overview of available methods for the conduct of remote tobacco-focused clinical trials across key aspects of the clinical trial pipeline.

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.

PURPOSE: Cannabis abstinence traditionally is the primary outcome in cannabis use disorder (CUD) treatment trials. Due to the changing legality of cannabis, patient goals, and preliminary evidence that suggests individuals who reduce their cannabis use may show functional improvements, cannabis reduction is a desirable alternative outcome in CUD trials. We review challenges in measuring cannabis reduction and the evidence to support various definitions of reduction. FINDINGS: Reduction in number of cannabis use days was associated with improvements in functioning across several studies. Reductions in quantity of cannabis used was inconsistently associated with improvements in functioning, though definitions of quantity varied across studies. Different biomarkers may be used depending on the reduction outcome. CONCLUSIONS: Biologically-confirmed reductions in frequency of cannabis use days may represent a viable endpoint in clinical trials for cannabis use disorder. Additional research is needed to better quantify reduction in cannabis amounts.

RATIONALE. Depression is common among individuals with cannabis use disorder (CUD), particularly individuals who present to CUD treatment. Treatments that consider this comorbidity are essential. OBJECTIVES. The goal of this secondary analysis was to examine whether N-Acetylcysteine (NAC) reduced depressive symptoms among adults (age 18–50) with CUD (N=302) and whether the effect of NAC on cannabis cessation varied as a result of baseline levels of depression. Bidirectional associations between cannabis use amount and depression were also examined. METHODS. Data for this secondary analysis were from a National Drug Abuse Treatment Clinical Trials Network (NIDA CTN) multi-site clinical trial for CUD. Adults with CUD (N=302) were randomized to receive 2400 mg of NAC daily or matched placebo for 12 weeks. All participants received abstinence-based contingency management. Cannabis quantity was measured by self-report, and weekly urinary cannabinoid levels (11-nor-9-carboxy-Δ9-tetrahydrocannabinol) confirmed abstinence. Depressive symptoms were measured by the Hospital Anxiety and Depression Scale. RESULTS. Depressive symptoms did not differ between the NAC and placebo groups during treatment. There was no significant interaction between treatment and baseline depression predicting cannabis abstinence during treatment. Higher baseline depression was associated with decreased abstinence throughout treatment and a significant gender interaction suggested that this may be particularly true for females. Cross-lagged panel models suggested that depressive symptoms preceded increased cannabis use amounts (in grams) during the subsequent month. The reverse pathway was not significant (i.e, greater cannabis use preceding depressive symptoms). CONCLUSIONS. Results from this study suggest that depression may be a risk factor for poor CUD treatment outcome and therefore should be addressed in the context of treatment. However, results do not support the use of NAC to concurrently treat co-occurring depressive symptoms and CUD in adults.

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.

BACKGROUND. Distress tolerance (DT) has been implicated as an important factor in the experience of negative affect (NA) and cannabis craving. However, previous research is limited by its use of laboratory paradigms that may not replicate in naturalistic settings. The current study examined how DT influenced reactivity to NA cues in daily life in a sample of frequent (≥3 times per week) cannabis-using emerging adults (age 18-21). METHODS. Using cue-reactivity ecological momentary assessment (CREMA), 63 (54% female; 85.7% white; M(age) = 19.62) participants reported on their cannabis craving and affect (sadness, relaxation) four semi-random times per day for two weeks (56 possible CREMA sessions/participant). We assessed affect and cannabis craving before and after exposure to neutral and NA cues. Multilevel modeling was used to examine within- and between-participant effects of cues, DT, and sex, as well as within- and between-participant average pre-cue affect and craving, on post-cue affect and craving. RESULTS. NA cues consistently predicted higher-than-normal post-cue sadness and lower relaxation, but not greater-than-normal post-cue craving. Cue type interacted with sex and DT to predict post-cue sadness, but not craving. Female participants and those reporting low DT reported higher sadness following NA cues compared to males and those with high DT, respectively. CONCLUSIONS. Frequent cannabis-using emerging adults differed in affect, but not cannabis craving, reactivity to NA cues as a function of sex and DT. Our results were partially consistent with prior human laboratory and CREMA research finding greater reactivity to NA cues among females and individuals with low DT.

Background There is robust preclinical literature and preliminary clinical findings supporting the use of N-Acetylcysteine (NAC) to treat substance use disorders, including tobacco use disorder (TUD). However, randomized controlled trials have yielded mixed results and NAC’s efficacy for TUD has not been established. The goals of this study were to assess the efficacy of NAC in promoting early and end-of-treatment abstinence and preventing relapse among adult smokers. Methods This randomized, double-blinded clinical trial enrolled adult, daily smokers (N = 114; ages 23–64; 51 % female; 65 % White; 29 % Black/African American; 7% Hispanic/Latinx), who were randomized 1:1 to receive NAC (n = 59) or placebo (n = 55) (1200 mg b.i.d.) for eight weeks. Participants received brief cessation counseling and incentives for abstinence during the first three days of the quit attempt. Primary outcomes: (i) carbon monoxide (CO)-confirmed abstinence during the first three days of the quit attempt. Secondary outcomes: (ii) time to relapse; (iii) biologically confirmed abstinence at Week 8. Results No differences were found between NAC and placebo groups on measures of early abstinence (3-day quit attempt; 11 % for NAC vs. 15 % for placebo; all p > 0.11), time to relapse (p = 0.19), and end-of-treatment abstinence (7% for NAC vs. 11 % for placebo; all p > 0.40]. Conclusions Results indicate that NAC is a well-tolerated pharmacotherapy but is unlikely to be efficacious as a monotherapy for TUD in adults. Considered in the collective context of other research, NAC may potentially be more useful in a younger population, as a combination pharmacotherapy, or in the presence of more intensive psychosocial treatment.

While the majority of youth who experiment with alcohol and drugs do not develop problematic levels of use, 5% of adolescents and 15% of young adults meet criteria for a substance use disorder (SUD). Pharmacotherapy, in combination with behavioral interventions, has the potential to increase the likelihood of successful treatment for youth struggling with SUD; however, the literature in this area is limited. To date, there are no Food and Drug Administration (FDA)-approved medications for adolescent SUD, other than buprenorphine, which has been approved down to 16 years of age for opioid use disorder. Despite alcohol and cannabis being the most commonly used substances during adolescence, only three medications have been tested among this demographic, and only two have warranted further study (i.e., naltrexone for alcohol and N-acetylcysteine for cannabis use disorder). Although less common in adolescents and young adults, the most promising pharmacological findings for this age group are for opioid (buprenorphine) and tobacco (bupropion and varenicline) use disorders. In addition, despite the recent marked increases in electronic nicotine delivery systems (i.e., vaping) among youth, treatment strategies are still in their infancy and no recommendation exists for how to promote cessation for youth vaping. Current findings are limited by: small, demographically homogeneous samples; few trials, including a substantial number of youth younger than 18; low retention; medication adherence rates; and minimal information on effective dosing levels and long-term outcomes. Overall, pharmacotherapy may be a potentially effective strategy to increase treatment effects; however, more rigorous research trials are warranted before FDA approval would be granted for any of the potential adjunctive medications in this age group.

Cannabis and tobacco co-use is prevalent, but consensus regarding the reasons for co-use among adults and the degree of interrelatedness between these substances is lacking. Reasons for co-use have been explored with younger users, but little data exists for more experienced users with entrenched patterns of co-use. The goal of this study was to examine characteristics and patterns of cannabis-tobacco co-use among adults in the Southeastern United States (US), where there is a legal landscape of generally restrictive cannabis legislation coupled with more permissive tobacco control compared to other US regions. Participants (N = 432) were regular cannabis users recruited through Amazon Mechanical Turk. Measures included demographics, patterns of cannabis and tobacco use, and reasons for co-use. Within this sample, 42% were current users of tobacco (n = 182). Cannabis-tobacco co-users were older and had more years of cannabis use than cannabis-only users. Among the co-using sub-sample, there was little consistency in the reasons for co-use, suggesting individual differences in the use of both substances. High levels of cannabis-tobacco interrelatedness (i.e., temporally concurrent use) were associated with smoking more cigarettes (tobacco) per day and greater nicotine dependence scores when compared to users with low levels of interrelatedness. Though these results are limited by a small sample size and generalizability issues, there were individual differences in cannabis-tobacco relatedness, which may be of importance when considering treatment strategies for cannabis, tobacco, or both. With additional research, personalized strategies adapted to cannabis-tobacco relatedness profiles among co-users may be warranted as a treatment strategy.

Objectives To assess the self-reported reasons for medical cannabis use within the southeastern United States and compare recreational and medical cannabis users. Methods This study was a cross-sectional survey administered in 2017 through Amazon's Mechanical Turk and enrolled 432 adult, regular cannabis users. Measures included demographics, cannabis use characteristics, and medical reasons for cannabis use. Results Under half (47%) of respondents endorsed using cannabis for both medical and recreational reasons and 12% reported medical use only. The most commonly cited reasons for medical cannabis use were psychiatric and 60 unique medical conditions were listed. Recreational and medical users were similar on several measures of current use, but did vary in their use history, methods of use, and product knowledge. Conclusions Despite state laws and conclusive scientific evidence to support medical cannabis use for certain conditions, cannabis is still used frequently for a range of medical issues. Policy Implications These data may assist healthcare providers in better understanding medical cannabis use in states with tightened restrictions and tailoring information to medical cannabis users about their specific conditions and prioritizing therapeutic options.

Background Concerns abound regarding childhood smartphone use, but studies to date have largely relied on self-reported screen use. Self-reporting of screen use is known to be misreported by pediatric samples and their parents, limiting the accurate determination of the impact of screen use on social, emotional, and cognitive development. Thus, a more passive, objective measurement of smartphone screen use among children is needed. Objective This study aims to passively sense smartphone screen use by time and types of apps used in a pilot sample of children and to assess the feasibility of passive sensing in a larger longitudinal sample. Methods The Adolescent Brain Cognitive Development (ABCD) study used passive, objective phone app methods for assessing smartphone screen use over 4 weeks in 2019-2020 in a subsample of 67 participants (aged 11-12 years; 31/67, 46% female; 23/67, 34% White). Children and their parents both reported average smartphone screen use before and after the study period, and they completed a questionnaire regarding the acceptability of the study protocol. Descriptive statistics for smartphone screen use, app use, and protocol feasibility and acceptability were reviewed. Analyses of variance were run to assess differences in categorical app use by demographics. Self-report and parent report were correlated with passive sensing data. Results Self-report of smartphone screen use was partly consistent with objective measurement (r=0.49), although objective data indicated that children used their phones more than they reported. Passive sensing revealed the most common types of apps used were for streaming (mean 1 hour 57 minutes per day, SD 1 hour 32 minutes), communication (mean 48 minutes per day, SD 1 hour 17 minutes), gaming (mean 41 minutes per day, SD 41 minutes), and social media (mean 36 minutes per day, SD 1 hour 7 minutes). Passive sensing of smartphone screen use was generally acceptable to children (43/62, 69%) and parents (53/62, 85%). Conclusions The results of passive, objective sensing suggest that children use their phones more than they self-report. Therefore, use of more robust methods for objective data collection is necessary and feasible in pediatric samples. These data may then more accurately reflect the impact of smartphone screen use on behavioral and emotional functioning. Accordingly, the ABCD study is implementing a passive sensing protocol in the full ABCD cohort. Taken together, passive assessment with a phone app provided objective, low-burden, novel, informative data about preteen smartphone screen use.

Objective Detentions and suspensions are common practices of school discipline, despite evidence that they are largely ineffective and disproportionately affect children from racial and ethnic minority backgrounds, particularly Black children, and children of lower socioeconomic status. However, few studies have examined suspension and detention rates among race, ethnicity, and family structure (single parent versus secondary caregiver) when controlling for typical behaviors associated with detention and suspension such as externalizing symptoms, age, sex, family income, family education, family conflict, and special education needs. Method Caregivers of 11,875 children between ages 9 and 10 years from the Adolescent Brain Cognitive Development (ABCD) study completed a questionnaire assessing their child’s demographics, family information, emotions and behaviors, and past-year school discipline history. Data were analyzed with logistic regression, implemented with a generalized estimating equations model. Results 5.4% of children received a detention or suspension. Controlling for typical predictors of behaviors, Black and multiracial Black children had up to 3.5 times greater odds of receiving a detention or suspension than White children; there were no disciplinary differences for Hispanic or Asian children compared to White children. Children from single-parent households had 1.4 times the odds of receiving detentions or suspensions than children in homes with a secondary caregiver. Conclusion Disciplinary actions that can impair typical childhood development, lead to academic failure and dropout, and cause significant emotional and psychological distress disproportionately affect Black children, multiracial Black children, and children from single-parent homes. Racism in elementary school discipline can perpetuate disparities in today’s educational system.

BACKGROUND: Nicotine vaping among youth has increased, warranting concern from tobacco control proponents. Many youth who vape indicate interest in quitting; however, few empirically supported vaping cessation interventions exist. This pilot feasibility study adapted an established behavioral intervention, contingency management (CM), delivered via telehealth to promote vaping cessation among young adults. METHODS: Participants (N=27; ages 17-21) vaping nicotine regularly were recruited via social media and digital advertisements from across the US (June 2020 - January 2021). Participants were randomized at approximately 4:1 to CM or Monitoring control (22:5). CM was delivered through DynamiCare Health’s smartphone app for 4 weeks, in which financial incentives were delivered contingent on abstinent cotinine samples after the quit day until the end of treatment (EOT; Days 7-28; 10 expected submissions). Control participants earned incentives for submitting cotinine, regardless of abstinence. Feasibility, acceptability, and abstinence was collected throughout treatment, at EOT, and at 1-month follow-up. RESULTS: The majority of enrolled participants completed treatment (Monitoring: 5/5; CM: 20/22), and intervention components were rated favorably overall (>80%). CM participants submitted 112/220 (55%) abstinent cotinine samples throughout the quit attempt, while the Monitoring group submitted 4/50 (8%) negative samples. There were no differences in abstinence between groups at EOT or follow-up. CONCLUSION: This pilot study of a telehealth-based youth vaping cessation intervention demonstrated preliminary feasibility and acceptability. These results suggest that CM for young adult vaping cessation, delivered remotely, is a promising direction for future work and fully powered trials are warranted to assess intervention efficacy.

BACKGROUND While there have been many technological advances in studying the neurobiological and clinical basis of tobacco use disorder and nicotine addiction, there have been relatively minor advances in technologies for monitoring, characterizing, and intervening to prevent smoking in real time. Better understanding of real-time smoking behavior can be helpful in numerous applications without the burden and recall bias associated with self-report. OBJECTIVE The goal of this study was to test the validity of using a smartwatch to advance the study of temporal patterns and characteristics of smoking in a controlled laboratory setting prior to its implementation in situ. Specifically, the aim was to compare smoking characteristics recorded by Automated Smoking PerceptIon and REcording (ASPIRE) on a smartwatch with the pocket Clinical Research Support System (CReSS) topography device, using video observation as the gold standard. METHODS Adult smokers (N=27) engaged in a video-recorded laboratory smoking task using the pocket CReSS while also wearing a Polar M600 smartwatch. In-house software, ASPIRE, was used to record accelerometer data to identify the duration of puffs and interpuff intervals (IPIs). The recorded sessions from CReSS and ASPIRE were manually annotated to assess smoking topography. Agreement between CReSS-recorded and ASPIRE-recorded smoking behavior was compared. RESULTS ASPIRE produced more consistent number of puffs and IPI durations relative to CReSS, when comparing both methods to visual puff count. In addition, CReSS recordings reported many implausible measurements in the order of milliseconds. After filtering implausible data recorded from CReSS, ASPIRE and CReSS produced consistent results for puff duration (R2=.79) and IPIs (R2=.73). CONCLUSIONS Agreement between ASPIRE and other indicators of smoking characteristics was high, suggesting that the use of ASPIRE is a viable method of passively characterizing smoking behavior. Moreover, ASPIRE was more accurate than CReSS for measuring puffs and IPIs. Results from this study provide the foundation for future utilization of ASPIRE to passively and accurately monitor and quantify smoking behavior in situ.

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.

Relative to adults, adolescents are at greater risk of developing a cannabis use disorder (CUD) and risk may be exacerbated by co-occurring depressive symptoms. N-Acetylcysteine (NAC), an over-the-counter antioxidant, is thought to normalize glutamate transmission. Oxidative stress and glutamate transmission are disrupted in both depression and CUD. Thus, NAC may be particularly effective at promoting cannabis abstinence among adolescents with elevated depressive symptoms. Secondary analyses were conducted using a sub-sample of adolescents with CUD (N = 74) who participated in an 8-week randomized placebo-controlled clinical trial examining the efficacy of NAC for cannabis cessation. It was hypothesized that NAC would reduce severity of depressive symptoms, and that decreases depressive symptom severity would mediate decreases in positive weekly urine cannabinoid tests (11-nor-9-carboxy-Δ9-tetrahydrocannabinol). Additionally, it was expected that adolescents with greater severity of baseline depressive symptoms would be more likely to become abstinent when assigned NAC relative to placebo. Results from linear mixed models and generalized estimating equations did not suggest that NAC reduced severity of depressive symptoms, and the hypothesis that NAC's effect on cannabis cessation would be mediated by reduced depressive symptoms was not supported. However, an interaction between treatment condition and baseline severity of depressive symptoms as a predictor of weekly urine cannabinoid tests was significant, suggesting that NAC was more effective at promoting abstinence among adolescents with heightened baseline depressive symptoms. These secondary findings, though preliminary, suggest a need for further examination of the role of depressive symptoms in treatment of adolescent CUD with NAC.

PURPOSE OF REVIEW: Adolescent cannabis use represents a significant public health concern. Cannabis experimentation typically begins in adolescence and increases the odds of meeting criteria for cannabis use disorder. Cannabis use disorder is associated with numerous short- and long-term adverse consequences for adolescents, highlighting the critical need for efficacious behavioral treatments. This brief review aims to synthesize the state of the behavioral treatment literature on adolescents with cannabis use disorder and to discuss new pathways to leverage neuroscience to inform novel targets for behavioral intervention. RECENT FINDINGS: To date, effective treatment options for adolescent cannabis use disorder that have been tested in randomized controlled trials include cognitive behavioral therapy, motivational enhancement therapy, and multidimensional family therapy. However, established behavioral treatment approaches focus on higher-order cognitive control and have only been modestly effective. SUMMARY: There is a need to develop new pathways that translate neuroscience findings into novel targets for behavioral interventions.

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.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.The mobile application (My Mobile Monitor, MParticipants 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.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.

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.

Background Individuals with alcohol use disorder (AUD) do not always respond to currently available treatments, and evaluation of new candidate pharmacotherapies is indicated. N-acetylcysteine (NAC), an over-the-counter supplement, has shown promise in treating a variety of substance use disorders, but little research has evaluated its merits as a treatment for AUD. This secondary analysis from the National Drug Abuse Treatment Clinical Trials Network examined the effects of NAC versus placebo on alcohol use among participants with cannabis use disorder (CUD) enrolled in a 12-week, multi-site cannabis cessation trial. Methods Participants (N = 302, ages 18–50) were randomized to double-blind NAC (1200 mg, twice daily) or placebo. Neither alcohol use nor desire for alcohol cessation were requirements for participation. Participants that returned for at least one treatment visit and had recorded alcohol use data (i.e., total drinks per week, drinking days per week, and binge drinking days per week) were included in the analysis (n = 277). Results Compared to the placebo group, participants in the NAC group had increased odds of between-visit alcohol abstinence [OR = 1.37; 95% CI = 1.06–1.78; p = 0.019], fewer drinks per week [RR = 0.67; 95% CI = 0.48–0.99; p = 0.045], and fewer drinking days per week [RR = 0.69; 95% CI = 0.51–0.92; p = 0.014]. Changes in concurrent cannabis use amounts were not correlated to any of the alcohol use variables. Discussion These findings indicate that NAC may be effective at reducing consumption of alcohol by ∼30% among treatment-seeking adults with CUD, suggesting a need for further trials focused on the effects of NAC on alcohol consumption among individuals seeking treatment for AUD.

Background Quantifying cannabis use is complex due to a lack of a standardized packaging system that contains specified amounts of constituents. A laboratory procedure has been developed for estimating physical quantity of cannabis use by utilizing a surrogate substance to represent cannabis, and weighing the amount of the surrogate to determine typical use in grams. Method This secondary analysis utilized data from a multi-site, randomized, controlled pharmacological trial for adult cannabis use disorder (N = 300), sponsored by the National Drug Abuse Treatment Clinical Trials Network, to test the incremental validity of this procedure. In conjunction with the Timeline Followback, this physical scale-based procedure was used to determine whether average grams per cannabis administration predicted urine cannabinoid levels (11-nor-9-carboxy-Δ9-tetrahydrocannabinol) and problems due to use, after accounting for self-reported number of days used (in the past 30 days) and number of administrations per day in a 12-week clinical trial for cannabis use disorder. Results Likelihood ratio tests suggest that model fit was significantly improved when grams per administration and relevant interactions were included in the model predicting urine cannabinoid level (X2 = 98.3; p Conclusions This study provides support for the use of a scale-based method for quantifying cannabis use in grams. This methodology may be useful when precise quantification is necessary (e.g., measuring reduction in use in a clinical trial).

Background An efficacious pharmacotherapy for cannabis use disorder (CUD) has yet to be established. This study preliminarily evaluated the safety and efficacy of varenicline for CUD in a proof-of-concept clinical trial. Methods Participants in this 6-week randomized, placebo-controlled pilot trial received either varenicline (n = 35) or placebo (n = 37), added to a brief motivational enhancement therapy intervention. Outcomes included cannabis withdrawal, cannabis abstinence, urine cannabinoid levels, percent cannabis use days, and cannabis sessions per day. Results Both treatment groups noted significant decreases in self-reported cannabis withdrawal, percentage of days used, and use sessions per day during treatment compared to baseline. While this pilot trial was not powered to detect statistically significant between-group differences, participants randomized to varenicline evidenced numerically greater rates of self-reported abstinence at the final study visit [Week 6 intent-to-treat (ITT): Varenicline: 17.1% vs. Placebo: 5.4%; RR = 3.2 (95% CI: 0.7,14.7)]. End-of-treatment urine creatinine corrected cannabinoid levels were numerically lower in the varenicline group and higher in the placebo group compared to baseline [Change from baseline: Varenicline -1.7 ng/mg (95% CI: -4.1,0.8) vs. Placebo: 1.9 ng/mg (95% CI: -0.4,4.3); Δ = 3.5 (95% CI: 0.1,6.9)]. Adverse events related to study treatment did not reveal new safety signals. Conclusions Findings support the feasibility of conducting clinical trials of varenicline as a candidate pharmacotherapy for CUD, and indicate that a full-scale efficacy trial, powered based on effect sizes and variability yielded in this study, is warranted.

Objective: Given evidence that posttraumatic stress disorder (PTSD) is moderately heritable, a number of studies utilizing candidate gene approaches have attempted to examine the potential contributions of theoretically relevant genetic variation. Some of these studies have found sup port for a brain-derived neurotrophic factor (BDNF) variant, Val66Met, in the risk of developing PTSD, while others have failed to find this link. Methods: This study sought to reconcile these conflicting findings using a meta-analysis framework. Analyses were also used to determine whether there is significant heterogeneity in the link between this variant and PTSD. We conducted a systematic review of the literature on BDNF and PTSD from the PsycINFO and PubMed databases. A total of 11 studies were included in the analysis. Results: Findings indicate a marginally significant effect of the BDNF Val66Met variant on PTSD (p < 0.1). However, of the 11 studies included, only 2 suggested an effect with a non-zero confidence interval, one of which showed a z score of 3.31. We did not find any evidence for heterogeneity. Conclusions: Findings from this meta-analytic investigation of the published literature provide little support for the Val66Met variant of BDNF as a predictor of PTSD. Future well-powered agnostic genome-wide association studies with more refined phenotyping are needed to clarify genetic influences on PTSD.

Aims Current adolescent alcohol treatments have modest effects and high relapse rates. Evaluation of novel pharmacotherapy treatment is warranted. N-acetylcysteine (NAC), an over-the-counter antioxidant supplement with glutamatergic properties, is a promising treatment for marijuana cessation in adolescents; however, its effects on adolescent drinking have not been examined. To that end, this secondary analysis evaluated: (1) the effect of NAC vs. placebo on alcohol use over an eight-week adolescent marijuana cessation trial and (2) the role of marijuana cessation and reduction on subsequent alcohol use. Methods Marijuana-dependent adolescents (ages 15–21; N = 116) interested in treatment were randomized to NAC 1200 mg or matched placebo twice daily for eight weeks. Participants were not required to be alcohol users or interested in alcohol cessation to qualify. Results There were no demographic or baseline alcohol use differences between participants randomized to NAC vs. placebo (ps > 0.05). Of the 89 participants returning for ≥ one visit following randomization, 77 reported ≥ one alcoholic drink in the 30 days prior to study entry and averaged 1.3 (SD = 1.4) binge drinking days per week. During treatment, less marijuana use (measured via urine cannabinoid levels) was associated with less alcohol use in the NAC-treated group but not in the placebo-treated group (p = 0.016). Conclusions There was no evidence of compensatory alcohol use during marijuana treatment. In fact, in the NAC group, lower levels of marijuana use were associated with less alcohol use, suggesting NAC effects may generalize to other substances and could be useful in decreasing adolescent alcohol use. NAC trials specifically focused on alcohol-using adolescents are warranted.

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. SUMMARY: 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.

RATIONALE: Female cigarette smokers tend to show greater cessation failure compared to males. Variables that contribute to the maintenance of smoking, including stress and craving, may differentially impact male and female smokers. Novel pharmacotherapies, such as oxytocin, may attenuate stress reactivity and craving in smokers, but work in this area is limited. OBJECTIVES: This study assessed the influence of gender and oxytocin on stress reactivity, craving, and smoking in a randomized, placebo-controlled laboratory relapse paradigm. METHODS: Male and female adult cigarette smokers (ages 18–45) were enrolled (women oversampled 2:1) and completed a laboratory session, in which intranasal oxytocin or placebo was administered followed by a laboratory social stress task. The role of gender and oxytocin were assessed on measures of stress reactivity, cigarette craving, latency to smoke in a resistance task, subjective responses to smoking, and ad-libitum smoking. RESULTS: Participants (N=144) had a mean age of 31, were 63% female and 56% White. Following stress induction, female smokers evidenced greater subjective stress than males, though males demonstrated greater neuroendocrine reactivity and smoking intensity than females. No gender differences were demonstrated for craving. Oxytocin did not attenuate any aspect of stress reactivity, craving, smoking, or subjective responses to smoking compared to placebo. CONCLUSIONS: Gender differences in stress reactivity were shown in the hypothesized direction, but oxytocin appeared to exert little impact on subjective or behavioral metrics. Results highlight the complex relationship between gender, stress, and smoking, as well as the implications for oxytocin as a potential pharmacotherapy for smoking cessation.

OBJECTIVES: To assess the self-reported reasons for medical cannabis use within the southeastern United States and compare recreational and medical cannabis users. METHODS: This study was a cross-sectional survey administered in 2017 through Amazon’s Mechanical Turk and enrolled 432 adult, regular cannabis users. Measures included demographics, cannabis use characteristics, and medical reasons for cannabis use. RESULTS: Under half (47%) of respondents endorsed using cannabis for both medical and recreational reasons and 12% reported medical use only. The most commonly cited reasons for medical cannabis use were psychiatric and 60 unique medical conditions were listed. Recreational and medical users were similar on several measures of current use, but did vary in their use history, methods of use, and product knowledge. CONCLUSIONS: Despite state laws and conclusive scientific evidence to support medical cannabis use for certain conditions, cannabis is still used frequently for a range of medical issues. POLICY IMPLICATIONS: These data may assist healthcare providers in better understanding medical cannabis use in states with tightened restrictions and tailoring information to medical cannabis users about their specific conditions and prioritizing therapeutic options.

Treatment development and evaluation for substance use disorders are hindered when randomized controlled trials fail to show a treatment effect when one exists. This manuscript provides an overview of addressable methodological factors that may contribute to incorrect trial results. The collection of remote, naturalistic, real-time adherence and substance use data through ambulatory assessment methods in everyday life is presented as a partial solution. Other recommendations related to participant recruitment and selection, ensuring adequate consistency/fidelity and dose of treatment, and rigorously assessing clinical outcomes are discussed. With implementation of eligibility criteria verification, treatment adherence monitoring, and remote assessment of substance use and biomarkers, ambulatory assessment may help improve clinical trial success rates by improving precision, increasing reproducibility, and reducing the impact of methodological issues that may lead to inaccurate trial results.

The prevalence of cannabis use disorder (CUD) varies with age. Adolescents are particularly susceptible to negative consequences associated with heavy cannabis use. In this chapter, the age-related trends in CUD are discussed. Neurobiological risk factors associated with increased risk of developing a CUD are also discussed, including impulsivity/disinhibition, emotional dysregulation, and sensitivity to the rewarding properties of cannabis. Environmental risk factors such as low parental monitoring, parental cannabis use, and association with peers who use cannabis may contribute to cannabis use initiation in adolescence, indirectly influencing the development of CUD. Evidence for behavioral and pharmacological treatments for adolescent CUD is reviewed. More research is available on behavioral treatments for adolescent CUD, and these are often the first-line treatment options. Emerging evidence suggests promising pharmacological adjuncts for the treatment of adolescent CUD, however. Preliminary data examining these pharmacological treatments suggests that effective treatments for adults may not be appropriate or effective for adolescents and vice versa, though further research is necessary.

Background While there have been many technological advances in studying the neurobiological and clinical basis of tobacco use disorder and nicotine addiction, there have been relatively minor advances in technologies for monitoring, characterizing, and intervening to prevent smoking in real time. Better understanding of real-time smoking behavior can be helpful in numerous applications without the burden and recall bias associated with self-report. Objective The goal of this study was to test the validity of using a smartwatch to advance the study of temporal patterns and characteristics of smoking in a controlled laboratory setting prior to its implementation in situ. Specifically, the aim was to compare smoking characteristics recorded by Automated Smoking PerceptIon and REcording (ASPIRE) on a smartwatch with the pocket Clinical Research Support System (CReSS) topography device, using video observation as the gold standard. Methods Adult smokers (N=27) engaged in a video-recorded laboratory smoking task using the pocket CReSS while also wearing a Polar M600 smartwatch. In-house software, ASPIRE, was used to record accelerometer data to identify the duration of puffs and interpuff intervals (IPIs). The recorded sessions from CReSS and ASPIRE were manually annotated to assess smoking topography. Agreement between CReSS-recorded and ASPIRE-recorded smoking behavior was compared. Results ASPIRE produced more consistent number of puffs and IPI durations relative to CReSS, when comparing both methods to visual puff count. In addition, CReSS recordings reported many implausible measurements in the order of milliseconds. After filtering implausible data recorded from CReSS, ASPIRE and CReSS produced consistent results for puff duration (R2=.79) and IPIs (R2=.73). Conclusions Agreement between ASPIRE and other indicators of smoking characteristics was high, suggesting that the use of ASPIRE is a viable method of passively characterizing smoking behavior. Moreover, ASPIRE was more accurate than CReSS for measuring puffs and IPIs. Results from this study provide the foundation for future utilization of ASPIRE to passively and accurately monitor and quantify smoking behavior in situ.

Rationale Natural disasters are common and have potentially deleterious impacts on individuals, as well as on the relationships among family members (Adams et al., 2015; Paul, 2015). Additionally, caregiver-, offspring-, and family-level outcomes are often correlated following disaster. Objective Thus, longitudinal work is needed to clarify the prospective associations among such constructs following severe disasters. Method The current study included 1,271 adolescents and investigated whether disaster exposure impacted adolescent posttraumatic stress disorder (PTSD) symptoms, parent distress, and family parent-child conflict and communication, as well as whether/how these factors influenced one another over time. This study used a dynamic cascade model and included adolescents (ages 12-17) and caregivers present for tornadoes in Missouri and Alabama in 2011. These participants were part of a larger study involving a web-based intervention. Results Over and above covariates (i.e., adolescent age, gender, race, treatment, prior trauma, adolescent alcohol use and depressive symptoms, and household income), families who experienced greater severity of disaster exposure had adolescents who reported more baseline PTSD symptoms and caregivers who reported more distress at baseline. Conclusions Providing tangible resources (e.g., housing, food, transportation, essential possessions) to families post-disaster may reduce parent distress and adolescent PTSD symptoms. Additionally, reducing adolescent PTSD symptoms may prospectively improve relationships between parents and adolescents.

Background In light of recent progress toward pharmacologic interventions to treat adolescent cannabis use disorder, it is important to consider which adolescent characteristics may be associated with a favorable response to treatment. This study presents secondary analyses from a parent randomized controlled trial of N -acetylcysteine (NAC) in adolescents with cannabis use disorder. We hypothesized that high pretreatment impulsivity and medication non-adherence would be associated with reduced abstinence rates. Methods Participants were treatment-seeking adolescents ( N =115) who met criteria for cannabis use disorder and were assessed for pretreatment impulsivity. They received 1200mg NAC or placebo orally twice daily for 8weeks. An intent-to-treat analysis using a repeated-measures logistic regression model was used to relate pretreatment impulsivity (Barratt Impulsiveness Scale) and treatment group to abstinence rates, measured by urine cannabinoid tests. To explore mechanisms by which NAC may reduce cannabis use, relationships between impulsivity, adherence, and abstinence were assessed in a second statistical model using data from participants with recorded adherence and urine cannabinoid test results ( n =54). Results In the intent-to-treat analysis, low pretreatment impulsivity, NAC treatment, and negative baseline urine cannabinoid test results independently increased the odds of having negative urine cannabinoid tests during treatment (OR=2.1, 2.3, and 5.3 respectively). In the sample of participants with adherence data ( n =54), adherence tripled the odds of abstinence. Notably, the effect of adherence on abstinence was only observed in the NAC treatment group. Lastly, although the highly impulsive participants had reduced rates of abstinence, highly impulsive individuals adherent to NAC treatment had increased abstinence rates compared to non-adherent individuals. Conclusion Low impulsivity, NAC treatment, medication adherence, and baseline negative cannabinoid testing were associated with increased rates of abstinence in adolescents seeking treatment for cannabis use disorder. Efforts to optimize pharmacotherapy adherence may be particularly crucial for highly impulsive individuals. Understanding and addressing factors, such as impulsivity and adherence, which may affect outcomes, may aid in the successful evaluation and development of potentially promising pharmacotherapies.

Adverse childhood experiences (ACE) are associated with greater neuroendocrine responses to social stress in substance users. The neuropeptide oxytocin might attenuate this relationship. Given sex differences in ACE exposure and neuroendocrine stress reactivity, it is unknown whether this association is similar for males and females. Therefore, this secondary analysis evaluated the interactive effect of sex, ACE, and acute oxytocin administration on neuroendocrine stress responses in adult cigarette smokers (N = 144). Participants completed the Adverse Childhood Experiences Questionnaire at screening and were randomized to receive intranasal oxytocin or placebo before undergoing the Trier Social Stress Task (TSST). Cortisol levels were assessed at pre- and post-medication administration and at 20 and 40 min following the TSST. Generalized linear mixed models were developed to predict post-TSST cortisol levels. Predictors included treatment assignment (placebo vs. oxytocin), sex (male vs. female), ACE (0–10 total score), pre-medication cortisol levels, and minutes since medication administration. The hypothesized three-way interaction between sex, oxytocin, and ACE scores was significant. Linear associations between ACE scores and cortisol reactivity indicated higher ACE scores were associated with attenuated cortisol response in females, regardless of treatment condition. For males, higher ACE scores were associated with heightened cortisol response, an effect that was attenuated by oxytocin. Results indicate that the association between ACE and neuroendocrine reactivity to social stress, as well as the attenuating effect of oxytocin, is differentially impacted by sex. Males with greater childhood adversity may be more likely to benefit from oxytocin’s anxiolytic properties.

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.

Importance Cigarette smoking is the leading cause of preventable morbidity and mortality in the United States and worldwide, and most tobacco users begin smoking in adolescence. Although advances have yielded efficacious pharmacotherapies to complement smoking cessation counseling in adults, far less progress has been made in addressing tobacco use in adolescence. Objective To evaluate the efficacy and safety of varenicline tartrate for smoking cessation in adolescents and young adults. Design, Setting, and Participants This 2-group randomized, placebo-controlled, double-blind intention-to-treat clinical trial enrolled a volunteer sample of treatment-seeking adolescent and young adult cigarette smokers (n = 157) aged 14 to 21 years at an outpatient clinical site in Charleston, South Carolina, from August 15, 2012, to October 20, 2017. Follow-up was completed on January 25, 2018. Data were analyzed from March 19, 2018, to August 11, 2018, with further revisions completed April 10, 2019. Interventions Participants were randomized in a 1:1 ratio to a 12-week course of varenicline (n = 77) or placebo (n = 80). All participants received weekly smoking cessation counseling. Main Outcomes and Measures The preselected primary efficacy outcome was urine cotinine level–confirmed 7-day abstinence at the end of treatment. Secondary efficacy outcomes included weekly abstinence throughout active treatment, abstinence at posttreatment follow-up visits, and time to first 7-day abstinence. The primary safety outcome was the frequency of treatment-emergent adverse events. Results A total of 157 participants were enrolled (94 male [59.9%]; mean [SD] age, 19.1 [1.5] years). The varenicline and placebo groups did not differ in the primary outcome of cotinine-confirmed self-reported 7-day abstinence at the end of treatment (varenicline group, 4 of 45 [8.9%]; placebo group, 4 of 45 [8.9%]; risk ratio [RR], 0.97; 95% CI, 0.29-2.99;P = .96). However, among secondary outcomes, the varenicline group achieved self-reported earlier abstinence of at least 7 days (hazard ratio, 1.91; 95% CI, 1.12-3.27) and demonstrated higher rates of self-reported weekly abstinence during the full course of treatment (RR, 1.81; 95% CI, 1.09-2.99;P = .02) and at posttreatment follow-up (RR, 1.82; 95% CI, 1.01-3.28;P = .02). Study medication was generally well tolerated, and treatment-emergent adverse events did not differ between groups (any adverse events, 55 [71.4%] in the varenicline group vs 60 [75.0%] in the placebo group; RR, 0.95; 95% CI, 0.79-1.15;P = .61). Conclusions and Relevance When added to weekly cessation counseling for adolescent cigarette smokers, varenicline, compared with placebo, was well tolerated but did not improve end-of-treatment abstinence. However, varenicline may hasten abstinence and yield improvements in posttreatment abstinence outcomes. Trial Registration ClinicalTrials.gov identifier:NCT01509547

BACKGROUND: Despite the high prevalence of blunt smoking among cannabis users, very few studies examine the clinical profile of blunt smokers relative to those using more common methods of cannabis use, such as joints. METHODS: The current study uses baseline data from the ACCENT (Achieving Cannabis Cessation-Evaluating N-acetylcysteine Treatment) study, a multi-site randomized pharmacotherapy clinical trial within the National Drug Abuse Treatment Clinical Trials Network, to predict the association between blunt and joint use frequency and cannabis use characteristics (e.g., grams of cannabis used) and consequences (e.g., withdrawal) among past-month cannabis users (N = 377) who were screened for study participation. RESULTS: After controlling for race, age, gender, other forms of cannabis use (including joint use) and nicotine dependence, multivariable linear regression models indicated that the number of days of blunt use in the past month was a significant predictor of the average amount of cannabis per using day (t = 3.04, p < .01), the estimated average cost of cannabis (t = 2.28, p < .05) and Cannabis Withdrawal Scale scores (t = 1.94, p < .05). Frequency of joint use did not significantly predict any of the cannabis use characteristics or consequences. CONCLUSIONS: Blunt smokers may present to treatment with greater amounts of cannabis smoked and more intense withdrawal symptoms, which may adversely impact their likelihood of successful abstinence. Cannabis-dependent blunt smokers may be more likely to benefit from treatment that targets physiological and mood-related withdrawal symptoms.