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Aims: Substance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions. Design, Setting and Participants: We used a Delphi approach with two sequential phases: survey development and iterative surveying of experts. This was an on-line study. During survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n = 54) identified via recommendations from the Steering Committee and a systematic review. Measurements: Survey with 67 items covering four key areas of intervention development: targets, intervention approaches, active ingredients and modes of delivery. Findings: Across two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty-titration, bias modification, goal-setting, strategy learning and meta-awareness as active ingredients; and (iv) both addiction treatment work-force and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities. Conclusions: Expert recommendations on cognitive training and remediation for substance use disorders highlight the relevance of targeting implicit biases, reward, emotion regulation and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options., Medical Research Future Fund (MRFF) MRF1141214, National Health and Medical Research Council (NHMRC) of Australia GNT2009464

ImportanceThe prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or “Long COVID”) in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.ObservationsWe describe the protocol for the Pediatric Observational Cohort Study of the NIH’sREsearchingCOVID toEnhanceRecovery (RECOVER) Initiative. RECOVER-Pediatrics is an observational meta-cohort study of caregiver-child pairs (birth through 17 years) and young adults (18 through 25 years), recruited from more than 100 sites across the US. This report focuses on two of five cohorts that comprise RECOVER-Pediatrics: 1) ade novoRECOVER prospective cohort of children and young adults with and without previous or current infection; and 2) an extant cohort derived from the Adolescent Brain Cognitive Development (ABCD) study (n=10,000). Thede novocohort incorporates three tiers of data collection: 1) remote baseline assessments (Tier 1, n=6000); 2) longitudinal follow-up for up to 4 years (Tier 2, n=6000); and 3) a subset of participants, primarily the most severely affected by PASC, who will undergo deep phenotyping to explore PASC pathophysiology (Tier 3, n=600). Youth enrolled in the ABCD study participate in Tier 1. The pediatric protocol was developed as a collaborative partnership of investigators, patients, researchers, clinicians, community partners, and federal partners, intentionally promoting inclusivity and diversity. The protocol is adaptive to facilitate responses to emerging science.Conclusions and RelevanceRECOVER-Pediatrics seeks to characterize the clinical course, underlying mechanisms, and long-term effects of PASC from birth through 25 years old. RECOVER-Pediatrics is designed to elucidate the epidemiology, four-year clinical course, and sociodemographic correlates of pediatric PASC. The data and biosamples will allow examination of mechanistic hypotheses and biomarkers, thus providing insights into potential therapeutic interventions.Clinical Trials.gov IdentifierClinical Trial Registration:http://www.clinicaltrials.gov. Unique identifier:NCT05172011

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.

Background Polysubstance use is a common, problematic behavior that increases risk of harm to self and others. Research suggests that rates may vary based on gender, sex and sexuality. Understanding the current state of this literature may inform prevention and treatment of polysubstance use, leading to reduced public health burden. Objectives This review aimed to synthesize research on gender, sex and sexuality differences in polysubstance use in adults and adolescents. Methods A scoping review was conducted using all EBSCO databases, PubMed and Google Scholar to identify articles examining the effects of gender, sex and sexuality on polysubstance use. Polysubstance use was defined broadly as the use of any combination of substances over any time period and included licit (alcohol, tobacco) and illicit substances, concurrent and simultaneous use, from lifetime to daily use and use at any frequency. Studies were considered if they were published in peer-reviewed journals between January 1990 and October 2020 and were written in English. Publicly available data sources were also utilized to fully capture prevalence data that has not been published elsewhere. Results Findings were mostly inconsistent and often conflicting. Only two findings were generally consistent: adult men were overall more likely to report polysubstance use than adult women, and sexual and gender minorities report more frequent polysubstance use than non-minorities. Conclusions Research has been unable to clearly elucidate differences in polysubstance use prevalence and patterns according to gender, sex and sexuality. Several recommendations are offered to advance future research and address limitations of current research.

The human toll of disasters extends beyond death, injury and loss. Post-traumatic stress (PTS) can be common among directly exposed individuals, and children are particularly vulnerable. Even children far removed from harm’s way report PTS, and media-based exposure may partially account for this phenomenon. In this study, we examine this issue using data from nearly 400 9- to 11-year-old children collected before and after Hurricane Irma, evaluating whether pre-existing neural patterns moderate associations between hurricane experiences and later PTS. The ‘dose’ of both self-reported objective exposure and media exposure predicted PTS, the latter even among children far from the hurricane. Furthermore, neural responses in brain regions associated with anxiety and stress conferred particular vulnerability. For example, heightened amygdala reactivity to fearful stimuli moderated the association between self-reported media exposure and PTS. Collectively, these findings show that for some youth with measurable vulnerability, consuming extensive disaster-related media may offer an alternative pathway to disaster exposure that transcends geography and objective risk. Dick et al. show that in youth, post-traumatic stress related to Hurricane Irma was predicted by self-reported direct and media exposure. Furthermore, neural responses in brain regions associated with anxiety conferred particular vulnerability to media exposure.

Neuroscience has contributed to uncover the mechanisms underpinning substance use disorders (SUD). The next frontier is to leverage these mechanisms as active ingredients to create more effective interventions for SUD. Recent large-scale cohort studies are generating multiple levels of neuroscience-based information with potential to inform the development and refinement of future preventive strategies. However, there is still no available well-recognized frameworks to guide the integration of these complex datasets into prevention trial protocols. The Research Domain Criteria (RDoC) provides a neuroscience-based multi-system framework that is well suited to facilitate translation of neurobiological mechanisms into behavioural domains amenable to preventative interventions. We propose a novel RDoC-based framework for prevention science that organizes and advances the integration of technologies and findings from neuroscience into the refinement of current and construction of future preventive and early interventions. This neuroscience-informed framework categorizes addiction risk factors within the dysfunction of the five major RDoC constructs (Negative Valence Systems, Positive Valence Systems, Cognitive Systems, Arousal and Regulatory Systems, and Social Processes). We adapted the framework for the existing preventive interventions and categorized their components using RDoC constructs. From a systematic review of randomized controlled trials using a person-centered drug/alcohol preventive approach for adolescents (13-18 years), we identified 98 trials on 37 preventive interventions. We categorized them within this framework based on their potential target(s). By using this neuroscience-informed framework, distinct neurocognitive trajectories which have been recognized as precursors or risk factors for SUDs, can be targeted, and more importantly, the change processes can be evaluated to inform causal hypotheses. This framework can also inform individualized assessment, intervention development and outcome measurement in preventive interventions.

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 and AimsSubstance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions.DesignDelphi approach with two sequential phases: survey development and iterative surveying of experts.SettingOnline study.ParticipantsDuring survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n=53) identified via recommendations from the Steering Committee and a systematic review.MeasurementsSurvey with 67 items covering four key areas of intervention development, i.e., targets, intervention approaches, active ingredients, and modes of delivery.FindingsAcross two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions, and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training, and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty-titration, bias-modification, goal setting, strategy learning, and meta-awareness as active ingredients; and (iv) both addiction treatment workforce and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities.ConclusionsExpert recommendations on cognitive training and remediation for SUD highlight the relevance of targeting implicit biases, reward, emotion regulation, and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options.

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.

Despite the promising implications for novel immune therapeutics, few clinical trials have tested these therapies to date. An understanding of how immune pharmacotherapies influence complex alcohol use disorder (AUD) profiles, including subjective response to alcohol, is very limited. Initial findings show that ibudilast, a neuroimmune modulator, reduces rates of heavy drinking and measures of alcohol craving.This study is a secondary analysis of a 2-week clinical trial of ibudilast that enrolled a nontreatment-seeking sample with AUD. Eligible participants (N = 52) were randomized to receive ibudilast or matched placebo and completed daily diary assessments (DDAs) during the 2-week period. Each morning, participants reported on their mood and craving levels both before and during the previous day's drinking episode, as well as stimulation and sedation levels during the previous day's drinking episode. Multilevel models were used to compare the effects of ibudilast and placebo on subjective alcohol response. Exploratory analyses tested whether ibudilast moderated the relationship between daily stimulation/sedation and alcohol intake and whether withdrawal-related dysphoria moderated ibudilast's effects on subjective response.Ibudilast did not significantly alter mean levels of stimulation or sedation (p's 0.05). It did, however, moderate the effect of daily stimulation on drinking (p = 0.045). Ibudilast attenuated alcohol-induced increases in craving compared with placebo (p = 0.047), but not other subjective response measures. Ibudilast significantly tempered daily alcohol-induced changes in urge to drink and positive mood only among individuals without withdrawal-related dysphoria.Ibudilast's effects on subjective alcohol responses appear to be nuanced and perhaps most salient for individuals drinking for positive reinforcement as distinguished from those who drink to feel normal. Consistent with previous findings, reductions in alcohol craving may represent a primary mechanism of ibudilast's effects on drinking. The ecologically valid nature of DDAs provide a clinically useful window into how individuals experience alcohol's effects while taking ibudilast.

Alcohol and cannabis are the most commonly used substances during adolescence and are typically initiated during this sensitive neurodevelopmental period. The aim of this review is to provide a comprehensive overview of the most recent literature focused on understanding how these substances affect the developing brain.Articles included in this review were identified by entering 30 search terms focused on substance use, adolescence, and neurodevelopment into MEDLINE, Embase, PsycINFO, ProQuest Central, and Web of Science. Studies were eligible for inclusion if they longitudinally examined the effect of adolescent alcohol and/or cannabis use on structural or functional outcomes in 50 or more participants.More than 700 articles were captured by the search, and 43 longitudinal studies met inclusion criteria, including 18 studies focused on alcohol use, 13 on cannabis use, and 12 on alcohol and cannabis co-use.Existing studies suggest heavy alcohol and cannabis use during adolescence are related to small to moderate disruptions in brain structure and function, as well as neurocognitive impairment. The effects of alcohol use include widespread decreases in gray matter volume and cortical thickness across time; slowed white matter growth and poorer integrity; disrupted network efficiency; and poorer impulse and attentional control, learning, memory, visuospatial processing, and psychomotor speed. The severity of some effects is dependent on dose. Heavy to very heavy cannabis use is associated with decreased subcortical volume and increased frontoparietal cortical thickness, disrupted functional development, and decreased executive functioning and IQ compared to non-using controls. Overall, co-use findings suggest more pronounced effects related to alcohol use than to cannabis use. Several limitations exist in the literature. Sample sizes are relatively small and demographically homogenous, with significant heterogeneity in substance use patterns and methodologies across studies. More research is needed to clarify how substance dosing and interactions between substances, as well as sociodemographic and environmental factors, affect outcomes. Larger longitudinal studies, already underway, will help clarify the relationship between brain development and substance use.

Disrupted brain gamma-aminobutyric acid (GABA)/glutamate homeostasis is a promising target for pharmacological intervention in co-occurring bipolar disorder (BD) and cannabis use disorder (CUD). Gabapentin is a safe and well-tolerated medication, FDA-approved to treat other neurological diseases, that restores GABA/glutamate homeostasis, with treatment studies supporting efficacy in treating CUD, as well as anxiety and sleep disorders that are common to both BD and CUD. The present manuscript represents the primary report of a randomized, double-blind, placebo-controlled, crossover (1-week/condition), multimodal-MRI (proton-MR spectroscopy, functional MRI) pilot study of gabapentin (1200 mg/day) in BD + CUD (n = 22). Primary analyses revealed that (1) gabapentin was well tolerated and adherence and retention were high, (2) gabapentin increased dorsal anterior cingulate cortex (dACC) and right basal ganglia (rBG) glutamate levels and (3) gabapentin increased activation to visual cannabis cues in the posterior midcingulate cortex (pMCC, a region involved in response inhibition to rewarding stimuli). Exploratory evaluation of clinical outcomes further found that in participants taking gabapentin versus placebo, (1) elevations of dACC GABA levels were associated with lower manic/mixed and depressive symptoms and (2) elevations of rBG glutamate levels and pMCC activation to cannabis cues were associated with lower cannabis use. Though promising, the findings from this study should be interpreted with caution due to observed randomization order effects on dACC glutamate levels and identification of statistical moderators that differed by randomization order (i.e. cigarette-smoking status on rBG glutamate levels and pMCC cue activation). Nonetheless, they provide the necessary foundation for a more robustly designed (urn-randomized, parallel-group) future study of adjuvant gabapentin for BD + CUD.

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.

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.

OBJECTIVE: Adult and adolescent studies suggest increased motivational responses to cannabis cues among regular cannabis users. However, functional magnetic resonance imaging (fMRI) studies have not explored neural activation in response to visual cannabis cues among adolescents in the United States. Gaining a better understanding of the neural circuits related to cue-elicited craving during adolescence may shed light on the neural basis for the development of problematic cannabis use that could ultimately be targeted for interventions. METHODS: 41 non-treatment-seeking youth (ages 17–21; mean age = 18.83; 46.3% female) who reported regular cannabis use underwent fMRI scanning involving a visual cannabis cue task and completed self-report and biological measures. Whole-brain activation was examined for cannabis cues compared to non-cannabis cues, and for active versus passive cannabis cues. Associations between self-reported substance use and task activation were examined. RESULTS: Cannabis images were identifiable to adolescents and were rated as more rewarding than matched non-cannabis images (p < .05). Greater activation was found for the cannabis cues compared to non-cannabis cues in bilateral posterior cingulate, cuneus, fusiform, precuneus, inferior temporal and parahippocampal gyri, as well as left thalamus, medial frontal and superior frontal gyri. Cue-elicited activation was not significantly associated with self-reported cannabis use (ps > 0.05). No differences were observed for the active versus passive cue contrast. CONCLUSIONS: Cannabis-using youth show more activation to cannabis cues than non-cannabis cues in brain regions underlying incentive salience, reward, and visual attention. This task could be useful for future studies examining neural underpinnings of reward processes in adolescent cannabis users.

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.

Purpose Alcohol and cannabis are the most commonly used substances during adolescence and are typically initiated during this sensitive neurodevelopmental period. The aim of this review is to provide a comprehensive overview of the most recent literature focused on understanding how these substances affect the developing brain. Search methods Articles included in this review were identified by entering 30 search terms focused on substance use, adolescence, and neurodevelopment into MEDLINE, Embase, PsycINFO, ProQuest Central, and Web of Science. Studies were eligible for inclusion if they longitudinally examined the effect of adolescent alcohol and/or cannabis use on structural or functional outcomes in 50 or more participants. Search results More than 700 articles were captured by the search, and 43 longitudinal studies met inclusion criteria, including 18 studies focused on alcohol use, 13 on cannabis use, and 12 on alcohol and cannabis co-use. Discussion and conclusions Existing studies suggest heavy alcohol and cannabis use during adolescence are related to small to moderate disruptions in brain structure and function, as well as neurocognitive impairment. The effects of alcohol use include widespread decreases in gray matter volume and cortical thickness across time; slowed white matter growth and poorer integrity; disrupted network efficiency; and poorer impulse and attentional control, learning, memory, visuospatial processing, and psychomotor speed. The severity of some effects is dependent on dose. Heavy to very heavy cannabis use is associated with decreased subcortical volume and increased frontoparietal cortical thickness, disrupted functional development, and decreased executive functioning and IQ compared to non-using controls. Overall, co-use findings suggest more pronounced effects related to alcohol use than to cannabis use. Several limitations exist in the literature. Sample sizes are relatively small and demographically homogenous, with significant heterogeneity in substance use patterns and methodologies across studies. More research is needed to clarify how substance dosing and interactions between substances, as well as sociodemographic and environmental factors, affect outcomes. Larger longitudinal studies, already underway, will help clarify the relationship between brain development and substance 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 Screen media is among the most common recreational activities engaged in by children. The displacement hypothesis predicts that increased time spent on screen media activity (SMA) may be at the expense of engagement with other recreational activities, such as sport, music, and art. This study examined associations between non-educational SMA and recreational activity endorsement in 9–10-year-olds, when accounting for other individual (i.e., cognition, psychopathology), interpersonal (i.e., social environment), and sociodemographic characteristics. Methods Participants were 9254 youth from the Adolescent Brain Cognitive Development Study®. Latent factors reflecting SMA, cognition, psychopathology, and social environment were entered as independent variables into logistic mixed models. Sociodemographic covariates included age, sex, race/ethnicity, education, marital status, and household income. Outcome variables included any recreational activity endorsement (of 19 assessed), and specific sport (swimming, soccer, baseball) and hobby (music, art) endorsements. Results In unadjusted groupwise comparisons, youth who spent more time engaging with SMA were less likely to engage with other recreational activities (ps p > .05). Some marginal effects were observed: for every one SD increase in time spent on games and movies over more social forms of media, youth were at lower odds of engaging in recreational activities (adjusted odds ratio = 0·83, 95% CI 0·76–0·89). Likewise, greater general SMA was associated with lower odds of endorsing group-based sports, including soccer (0·93, 0·88–0·98) and baseball (0·92, 0·86–0·98). Model fit comparisons indicated that sociodemographic characteristics, particularly socio-economic status, explained more variance in rates of recreational activity engagement than SMA and other latent factors. Notably, youth from higher socio-economic families were up to 5·63 (3·83–8·29) times more likely to engage in recreational activities than youth from lower socio-economic backgrounds. Conclusions Results did not suggest that SMA largely displaces engagement in other recreational activities among 9–10-year-olds. Instead, socio-economic factors greatly contribute to rates of engagement. These findings are important considering recent shifts in time spent on SMA in childhood.

Categorical mental disorders are being recognized as suboptimal targets in clinical neuroscience due to poor reliability as well as high rates of heterogeneity within, and comorbidity between, mental disorders. As an alternative to the case-control approach, recent studies have focused on the relationship between neurobiology and latent dimensions of psychopathology. The current study aimed to investigate the relationship between brain structure and psychopathology in the critical preadolescent period when psychopathology is emerging. This study included baseline data from the Adolescent Brain and Cognitive Development (ABCD) Study® (n = 11,721; age range = 9-10 years; male = 52.2%). General psychopathology, externalizing, internalizing, and thought disorder dimensions were based on a higher-order model of psychopathology and estimated using Bayesian plausible values. Outcome variables included global and regional cortical volume, thickness, and surface area. Higher levels of psychopathology across all dimensions were associated with lower volume and surface area globally, as well as widespread and pervasive alterations across the majority of cortical and subcortical regions studied, after adjusting for sex, race/ethnicity, and parental education. The relationships between general psychopathology and brain structure were attenuated when adjusting for cognitive functioning. There was evidence of a relationship between externalizing psychopathology and frontal regions of the cortex that was independent of general psychopathology. The current study identified lower cortical volume and surface area as transdiagnostic biomarkers for general psychopathology in preadolescence. The widespread and pervasive relationships between general psychopathology and brain structure may reflect cognitive dysfunction that is a feature across a range of mental illnesses.

OBJECTIVE: Data on the neurodevelopmental and associated behavioral effects of light to moderate in utero alcohol exposure are limited. This retrospective investigation tested for associations between reported maternal prenatal alcohol use and psychological, behavioral, and neurodevelopmental outcomes in substance-naive youths. METHODS: Participants were 9,719 youths (ages 9.0 to 10.9 years) from the Adolescent Brain Cognitive Development Study. Based on parental reports, 2,518 (25.9%) had been exposed to alcohol in utero. Generalized additive mixed models and multilevel cross-sectional and longitudinal mediation models were used to test whether prenatal alcohol exposure was associated with psychological, behavioral, and cognitive outcomes, and whether differences in brain structure and resting-state functional connectivity partially explained these associations at baseline and 1-year follow-up, after controlling for possible confounding factors. RESULTS: Prenatal alcohol exposure of any severity was associated with greater psychopathology, attention deficits, and impulsiveness, with some effects showing a dose-dependent response. Children with prenatal alcohol exposure, compared with those without, displayed greater cerebral and regional volume and greater regional surface area. Resting-state functional connectivity was largely unaltered in children with in utero exposure. Some of the psychological and behavioral outcomes at baseline and at the 1-year follow-up were partially explained by differences in brain structure among youths who had been exposed to alcohol in utero. CONCLUSIONS: Any alcohol use during pregnancy is associated with subtle yet significant psychological and behavioral effects in children. Women should continue to be advised to abstain from alcohol consumption from conception throughout pregnancy.

As natural disasters increase in frequency and severity1, 2, mounting evidence reveals that their human toll extends beyond death, injury, and loss. Posttraumatic stress (PTS) can be common among directly exposed individuals, and children are particularly vulnerable3, 4. Curiously, PTS can even be found among youth far removed from harm’s way, and media-based exposure may partially account for this phenomenon5–8. Unfortunately, susceptibility to media effects has been difficult to characterize because most research is initiated post-event, precluding examination of pre-disaster factors. In this study, we mitigate this issue with data from nearly 400 9-to 11-year-old children collected prior to and after Hurricane Irma. We evaluate whether preexisting neural patterns moderate associations between hurricane experiences and later Irma-related PTS. We show that “dose” of both objective exposure and Irma-related media exposure predicted Irma-related PTS, the latter even among children dwelling thousands of kilometers away from the hurricane. Furthermore, we show, using pre-hurricane functional magnetic resonance imaging data, that neural responses in brain regions associated with anxiety and stress confer particular vulnerability to the psychological effects of hurricane exposure among certain children. Surprisingly, this was even the case for media exposure– we found that that right amygdala reactivity to fearful stimuli moderated the association between Irma-related media exposure and PTS symptoms, with the media-PTS association strongest for children showing pre-hurricane heightened amygdala reactivity to Fear vs Neutral Faces. In contrast, in bilateral orbitofrontal cortex and left parahippocampal gyrus, children showing a weak response to the Fear condition relative to the Neutral condition were especially susceptible to PTS as a result of Irma-related media exposure. Collectively, these findings run counter to outdated “bullseye” models of disaster exposure that assume negative effects are narrowly circumscribed around a disaster’s geographic epicenter9. In contrast, for some youth with measurable preexisting vulnerability, consumption of extensive disaster-related media appears to offer an alternative pathway to disaster exposure that transcends geography and objective risk. This preventable exposure should be considered in disaster-related mental health efforts.

This study estimates interest in quitting and past e-cigarette quit attempts among US adolescents who vape.

Background Neurocognitive deficits are common among youth with mental disorders, and patterns of aberrant brain function generally cross diagnostic boundaries. This study investigated associations between functional neurocircuitry and broad transdiagnostic psychopathology dimensions in the critical preadolescent period when psychopathology is emerging. Methods Participants were 9- to 10-year-olds from the Adolescent Brain Cognitive Development Study. Factor scores of general psychopathology, externalizing, internalizing, and thought disorder dimensions were calculated from a higher-order model of psychopathology using confirmatory factor analysis (N = 11,721) and entered as explanatory variables into linear mixed models to examine associations with resting-state functional connectivity (n = 9074) and neural activation during the emotional n-back task (n = 6146) when covarying for sex, race/ethnicity, parental education, and cognitive function. Results All dimensions of psychopathology were commonly characterized by hypoconnectivity within the dorsal attention and retrosplenial-temporal networks, hyperconnectivity between the frontoparietal and ventral attention networks and between the dorsal attention network and amygdala, and hypoactivation of the caudal middle frontal gyrus. Externalizing pathology was uniquely associated with hyperconnectivity between the salience and ventral attention networks and hyperactivation of the cingulate and striatum. Internalizing pathology was uniquely characterized by hypoconnectivity between the default mode and cingulo-opercular networks. Connectivity between the cingulo-opercular network and putamen was uniquely higher for internalizing pathology and lower for thought disorder pathology. Conclusions These findings provide novel evidence that broad psychopathology dimensions are characterized by common and dissociable patterns, particularly for externalizing pathology, of functional connectivity and task-evoked activation throughout neurocognitive networks in preadolescence.

Author(s): Lees, Briana; Aguinaldo, Laika; Squeglia, Lindsay M; Infante, Maria Alejandra; Wade, Natasha E; Hernandez Mejia, Margie; Jacobus, Joanna | Abstract: BackgroundYouth whose parents have alcohol use disorder (AUD) are at higher risk for earlier initiation and greater magnitude of alcohol use, and have a higher likelihood of developing an AUD than their peers without parental history of AUD. This increased risk may be partly attributable to altered development of inhibitory control and related neural circuitry. This study examined neural activation during a motor response inhibition Stop Signal Task (SST) in substance-naive youth aged 9 to 10nyears with and without parental family history of AUD.MethodsBaseline cross-sectional survey and functional magnetic resonance imaging (fMRI) data were drawn from 6,898 youth in the US-based Adolescent Brain Cognitive Development Study. Generalized additive mixed models were conducted to examine the association between maternal, paternal, and parental (both mother and father) family history of AUD with neural activation during successful and failed response inhibition. Family history interactions with sex and stratification by ethnicity were explored.ResultsOf 6,898 participants, 951 (14%) were family history positive for anynparental AUD. Paternal history of AUD was associated with greater activation for successful inhibition in the right medial orbital frontal gyrus, compared to youth with no family history. Maternal history of AUD was associated with greater activation for failed response inhibition among females in the cerebellum, compared to females with no such history. Parental history (both mother and father) of AUD was associated with greater activation during successful inhibition in the left paracentral gyri and left superior parietal lobule. Maternal history and parental history of AUD findings were accounted for by a family history of substance use disorder in general. All effect sizes were relatively small.ConclusionsSubstance-naive children with a parental family history of AUD exhibit greater neural activation in some regions of the fronto-basal ganglia and cerebellar networks when they successfully or unsuccessfully inhibit a response as compared to children with no such family history. This unique neural response pattern could reflect a compensatory response and may represent an inherent neurobiological vulnerability to risk-related behaviors in these youth which will be examined in future longitudinal analyses of this cohort.

Adolescence comprises a period of various developmental changes as individuals transition from childhood to adulthood. Cognitive features of adolescence include heightened reward sensitivity and underdeveloped cognitive control that contribute to risky behaviors, including escalating substance use. This chapter provides an overview of adolescent brain development and substance use behaviors. Primary focus concerns predictors and consequences of alcohol and cannabis use by adolescents, with a specific emphasis on the topics of neurocognition, as well as structural and functional brain measures. Secondarily, the chapter covers psychosocial and genetic contributors to substance use and the subsequent emergence of disordered use and other related psychopathologies. Prospective, longitudinal designs have greatly increased our knowledge of the complex relationship between adolescent brain development and substance use by teasing apart pre-existing vulnerabilities and consequential effects of substance use. Large, multi-site studies currently underway will help further disentangle the complicated picture of substance co-use, the interactive nature of psychopathology, demographic factors, health habits, and genetic vulnerabilities, among other important factors related to substance use. The overarching goal of this research is to inform early intervention and treatment of problematic substance use in adolescents.

OBJECTIVE: Changes in gray matter volume and thickness are associated with adolescent alcohol and cannabis use, but the impact of these substances on surface area remains unclear. The present study expands on previous findings to examine the impact of alcohol and cannabis on surface area before and after use initiation. METHOD: Scans for 69 demographically similar youth were obtained at baseline (ages 12–14 years; before substance use) and at 6-year follow-up (ages 17–21 years). Participants were classified into three groups based on substance use: alcohol use initiators (ALC, n = 23), alcohol and cannabis use initiators (ALC+CU, n = 23), and individuals with minimal substance use (

BACKGROUND: Few effective treatment options exist for cannabis-using youth. This pilot study aimed to test Approach Avoidance Training to reduce cannabis use with non-treatment seeking adolescents. METHODS: Eighty cannabis-using non-treatment-seeking adolescents (average age 19) were recruited from San Diego, California and Charleston, South Carolina, and randomized to complete either six sessions of Cannabis Approach Avoidance Task Training (CAAT-training) designed to reduce automatic approach biases for cannabis cues, or CAAT-sham training. Change in two primary outcome variables were examined: 1) cannabis approach bias and 2) percent cannabis use days over study enrollment. Change in percent alcohol use days over study enrollment was explored as a secondary outcome. RESULTS: A mixed models repeated measures analysis confirmed the group by time interaction effect for approach bias failed to reach statistical significance (p=.06). Significant group by time interaction effects (ps

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.