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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Electronic cigarettes (e-cigarettes) were first introduced in the U.S. market in 2006, with the more recent evolution of "pod-mod" e-cigarettes such as JUUL introduced in 2015. Although marketed as a smoking cessation tool, e-cigarettes are rarely used for this purpose in youth. This review aims to synthesize the literature regarding e-cigarette use among youth, and provides a resource for clinicians, educators, and families that helps answer commonly asked questions about e-cigarettes.Methods: PubMed, Scopus, and PsycINFO search was performed using search terms "Electronic Nicotine Delivery Systems," "e cigarettes," "e-cigarettes," "electronic cigarettes," "vaping," "JUUL," "e-cigs," and "vape pens." Search results were filtered to only include those related to adolescents and young adults.Results: E-cigarette use among youth is common, with rates of use increasing from 1.5% in 2011 to 20.8% in 2018. Pod mod devices such as JUUL have gained favor among youth for their sleek design, user-friendly function, desirable flavors, and ability to be used discreetly in places where smoking is forbidden. Adolescents are often uninformed about the constituents of e-cigarettes, and little is known about the long-term effects of e-cigarettes. Studies have suggested a "gateway" effect for combustible cigarettes and cannabis use.Conclusions: E-cigarette use is becoming increasingly common among youth, leading to a myriad of questions and concerns from providers, educators, and family members. More research is needed to determine the ultimate public health impact of e-cigarette use. The authors provide a summary table of frequently asked questions in order to help clarify these common concerns. [ABSTRACT FROM AUTHOR]

Early alcohol initiation is associated with negative, alcohol-related outcomes. While previous work identifies numerous risk factors for early use, the relative contributions of known predictors remains understudied. The current project addresses this gap by 1) prospectively predicting early alcohol initiation using measures of inhibition control, reward sensitivity, and contextual risk factors and 2) interrogating the relative importance of each domain. This study leverages multimodal data from substance-naïve youth enrolled in the Adolescent Brain Cognitive Development (ABCD) Study® (n=11,694). Early initiation was defined as consuming a full standard drink containing alcohol prior to age 16. Propensity scores were used to match alcohol initiators (n=348) with demographically similar non-initiators at a 1:2 ratio (n=696). Independent logistic regressions were conducted for each domain followed by additive, hierarchical models. The model of contextual factors (pseudo-R2=0.086, AUC=0.67) outperformed inhibition control (pseudo-R2=0.021, AUC=0.58) and reward sensitivity measures (pseudo-R2=0.020, AUC=0.59). The hierarchical model containing all measures (pseudo-R2=0.106, AUC=0.69) did not significantly improve the model of contextual factors alone (p>0.05). Examples of significant predictors (p<0.05) include externalizing behaviors, number of substances known, and non-religious alcohol sipping. Contextual risk factors were the strongest predictors of early alcohol use; however, more work is needed to understand the causal nature of this relationship. Measures of inhibition control and reward sensitivity were not adequate in distinguishing initiators from non-initiators. These findings add to a body of evidence that contextual factors play a major role in alcohol initiation while highlighting specific predictor variables that could inform youth alcohol prevention. • Contextual and social risk factors were most predictive of early alcohol initiation. • Behavioral and structural neural correlates of reward and inhibition were not. • Number of known substances and past sipping were most predictive of early use. [ABSTRACT FROM AUTHOR]

Background: Alcohol-induced blackouts are associated with the development of alcohol abuse and dependence, so it is important to consider potential neurobiological risk factors for experiencing this problem prior to the onset of substance use. This study examines whether neural activity during inhibitory processing might be atypical in substance-naïve youth who later experience alcohol-induced blackouts.Methods: We examined inhibitory processing during fMRI with a go/no-go task that requires withholding a prepotent response in substance-naïve youth who would later transition into heavy drinking (n=40) and youth who remain abstinent (n=20). After approximately 5 years of annual follow-up assessments, youth were classified as nondrinkers (n=20), and heavy drinking youth were classified as having experienced an alcohol-induced blackout (blackout+; n=20) or not (blackout-; n=20). Groups were matched on demographic variables, and youth who experienced blackouts were matched on follow-up substance use.Results: Prior to initiating substance use, blackout+ youth showed greater activation during inhibitory processing than nondrinkers and blackout- youth in frontal and cerebellar brain regions. Mean activation during correct inhibitory responses relative to go responses in the left and right middle frontal gyri at baseline predicted future blackout experience, after controlling for follow-up externalizing behaviors and lifetime alcohol consumption.Conclusions: Substance-naïve adolescents who later experience alcohol-induced blackouts show increased neural effort during inhibitory processing, as compared to adolescents who go on to drink at similar levels but do not experience blackouts and healthy, nondrinking controls, suggesting a neurobiological vulnerability to alcohol-induced memory impairments. [ABSTRACT FROM AUTHOR]

Abstract: Background: Alcohol-induced blackouts are associated with the development of alcohol abuse and dependence, so it is important to consider potential neurobiological risk factors for experiencing this problem prior to the onset of substance use. This study examines whether neural activity during inhibitory processing might be atypical in substance-naïve youth who later experience alcohol-induced blackouts. Methods: We examined inhibitory processing during fMRI with a go/no-go task that requires withholding a prepotent response in substance-naïve youth who would later transition into heavy drinking (n =40) and youth who remain abstinent (n =20). After approximately 5 years of annual follow-up assessments, youth were classified as nondrinkers (n =20), and heavy drinking youth were classified as having experienced an alcohol-induced blackout (blackout+; n =20) or not (blackout−; n =20). Groups were matched on demographic variables, and youth who experienced blackouts were matched on follow-up substance use. Results: Prior to initiating substance use, blackout+ youth showed greater activation during inhibitory processing than nondrinkers and blackout− youth in frontal and cerebellar brain regions. Mean activation during correct inhibitory responses relative to go responses in the left and right middle frontal gyri at baseline predicted future blackout experience, after controlling for follow-up externalizing behaviors and lifetime alcohol consumption. Conclusions: Substance-naïve adolescents who later experience alcohol-induced blackouts show increased neural effort during inhibitory processing, as compared to adolescents who go on to drink at similar levels but do not experience blackouts and healthy, nondrinking controls, suggesting a neurobiological vulnerability to alcohol-induced memory impairments. [Copyright &y& Elsevier]

Abstract: Background: Problems inhibiting non-adaptive behaviors have been linked to an increased risk for substance use and other risk taking behaviors in adolescence. This study examines the hypothesis that abnormalities in neural activation during inhibition in early adolescence may predict subsequent substance involvement. Methods: Thirty eight adolescents from local area middle schools, ages 12–14, with very limited histories of substance use, underwent functional magnetic resonance imaging (fMRI) as they performed a go/no-go task of response inhibition and response selection. Adolescents and their parents were then followed annually with interviews covering substance use and other behaviors. Based on follow-up data, youth were classified as transitioning to heavy use of alcohol (TU; n =21), or as healthy controls (CON; n =17). Results: At baseline, prior to the onset of use, youth who later transitioned into heavy use of alcohol showed significantly less activation than those who went on to remain non to minimal users throughout adolescence. Activation reductions in TU at baseline were seen on no-go trials in 12 brain regions, including right inferior frontal gyrus, left dorsal and medial frontal areas, bilateral motor cortex, cingulate gyrus, left putamen, bilateral middle temporal gyri, and bilateral inferior parietal lobules (corrected p <.01, each cluster ≥32 contiguous voxels). Conclusions: These results support the hypothesis that less neural activity during response inhibition demands predicts future involvement with problem behaviors such as alcohol and other substance use. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

The objective of this multi-modal neuroimaging study was to identify neuroscience-informed treatment targets for adolescent alcohol use disorder (AUD) by examining potential neural alterations associated with adolescent alcohol use. Adolescents (ages 17–19) who heavily used (n=49) or did not use alcohol (n=22) were recruited for a multi-modal neuroimaging protocol, including proton magnetic resonance spectroscopy within the dorsal anterior cingulate cortex (dACC) and an fMRI alcohol cue-reactivity task. The alcohol cue-reactivity task was analyzed across 11 a priori regions-of-interest (ROI), including the dACC, and in an exploratory whole-brain approach. Correlations were run between neurometabolite levels and alcohol cue-reactivity in the dACC. There were no significant group differences in absolute neurometabolite concentrations. Compared to the control group, the alcohol-using group exhibited heightened alcohol cue reactivity in the left amygdala ROI (p=0.04). The whole-brain approach identified higher alcohol cue reactivity in the alcohol-using group compared to controls in the amygdala and occipital regions, and lower reactivity in the parietal lobe. Whole-brain sex effects were noted, with females displaying higher reactivity regardless of group. No significant correlations were found between neurometabolite levels and alcohol cue-reactivity in the dACC. The null neurometabolic findings may be due to age, relatively low severity of alcohol use, and non-treatment-seeking status of the participants. Females showed overall higher reactivity to alcohol cues, indicating a sex effect regardless of alcohol use history. Higher amygdala reactivity in alcohol-using adolescents suggests that emotional processing related to alcohol cues may be a useful target for future adolescent AUD interventions. • Effective treatments for adolescent alcohol use disorder are needed. • Multimodal imaging can assess metabolic and behavioral effects of alcohol in youth. • No alcohol-related differences in neurometabolite levels measured with 1 H-MRS. • Alcohol use was related to increased reactivity to alcohol cues in the amygdala. • Females showed increased reactivity to alcohol cues, regardless of alcohol use. [ABSTRACT FROM AUTHOR]

Background: Cognitive Bias Modification (CBM) has garnered interest as a potential addiction treatment. CBM interventions such as Approach Avoidance Training (AAT) are designed to alter automatic tendencies to approach drugs or drug-related cues. In our previous work, the cannabis AAT (CAAT) reduced cannabis approach bias, which was related to reduced cannabis use, among 80 non-treatment-seeking cannabis-using youth (Jacobus et al., 2018). In this preliminary examination, a subsample of these youth underwent neuroimaging to explore CAAT's effect on cannabis cue-related neural activation.Methods: Sub-study participants were 41 cannabis-using youth ages 17-21 (mean age = 18.83; 47.5% female). Participants completed a cannabis cue-reactivity task during a functional MRI scan pre- and post CAAT-training or CAAT-sham to examine CAAT-related neural changes.Results: Thirty-seven youth completed all six CAAT (n = 19) or CAAT-sham (n = 18) training sessions and had usable neuroimaging data. The group*time interaction on cannabis approach bias reached trend-level significance (p = .055). Change in approach bias slopes from pre-to post-treatment was positive for CAAT-sham (increased approach bias) and negative for CAAT-training (change to avoidance bias), consistent with the larger study. No significant changes emerged for cannabis cue-induced activation following CAAT-training or CAAT-sham in whole brain or region of interest analyses. However, active CAAT-training was associated with small-to-medium decreases in amygdala (Cohen's dz = 0.36) and medial prefrontal cortex (Cohen's dz = 0.48) activation to cannabis cues.Conclusions: Despite reducing cannabis use in the larger sample, CAAT-training did not alter neural cannabis cue-reactivity in the sub-study compared to CAAT-sham. More research is needed to understand neural mechanisms underlying AAT-related changes in substance use. [ABSTRACT FROM AUTHOR]

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 was 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 < 0.05) predicted percent days of cannabis and alcohol use over study enrollment. Participants randomized to the avoid cannabis condition (CAAT-training) reported 7% fewer days of cannabis use compared to 0% change for sham; unexpectedly, those in the avoid cannabis condition reported 10% percent more alcohol use days compared to 3% more for sham.Conclusions: Computerized cognitive bias modification paradigms may have utility in reducing adolescent cannabis use. Future work should consider developing a paradigm that addresses both cannabis and alcohol, as well as alternative computerized approaches for coping with addictive behavior in conjunction with bias modification. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: There are significant knowledge gaps of the vulnerabilities faced by youth from families with histories of alcohol or substance misuse. This study aimed to provide a comprehensive assessment of problems experienced by substance-naive children with positive family histories of substance misuse (FHP).Methods: Baseline data from up to 11,873 children (52.1 % male), aged 9.0-10.9 years (M = 9.9 ± 0.6), enrolled in the US-based Adolescent Brain Cognitive Development Study® were utilized. Mixed models tested cross-sectional associations between family history of substance misuse, assessed categorically and continuously, with neurobiological, cognitive, behavioral, and psychological outcomes, when controlling for confounding factors, including family history of psychopathology, and correcting for multiple comparisons.Results: One in four (26.3 %) youth were categorized as FHP (defined as ≥ one parent or ≥ two grandparents with misuse history). Controlling for confounding, FHP youth exhibited thinner whole cortices and greater surface area in frontal and occipital regions than youth with no such history (|ds|≥0.04, ps<.001). FHP youth experienced greater psychopathology and sleep disturbance (|ds|≥0.36, ps<.001) and were more likely to be diagnosed with multiple mental disorders (odds ratios≥1.22, ps<.001), with severity of effects dependent on family history density of substance misuse. Differences in cognition, impulsivity, and motivation were non-significant. Psychopathology, mental disorders, and sleep disturbance were negatively correlated with various neural indices (|rs|=0.01-0.05, ps<.05).Conclusions: At age 9-10 years, FHP youth can experience numerous problems, with psychopathology and mental disorders being some of the most significant. Therefore, prevention efforts should target psychopathology vulnerabilities in FHP children. [ABSTRACT FROM AUTHOR]

Background: Early alcohol use initiation is one of the strongest predictors of alcohol use disorders. Identifying modifiable risk factors for problematic alcohol use can guide prevention initiatives. Globally, approximately 10% of women consume alcohol during pregnancy, however the impact of prenatal alcohol exposure (PAE) on offspring alcohol use patterns has been understudied. The aim of this study was to examine associations between PAE and preadolescent alcohol use behaviors.Methods: Cross-sectional data were utilized from 10,119 children aged 9.0-10.9 years (M = 9.9, SD = 0.6) enrolled in the Adolescent Brain Cognitive Development Study®, based in the United States. Linear mixed models tested associations between PAE and endorsement of non-religious alcohol sipping in offspring, when adjusting for confounding factors.Results: In total, 2675 (26.4 %) youth were prenatally exposed to alcohol. Among PAE youth, total standard drinks consumed during pregnancy ranged from 0.4-90.0 drinks (M = 26.8, SD = 24.5). Compared to unexposed youth, those with any alcohol exposure during early pregnancy (∼0-7 weeks) were 1.7 times (95 % CI 1.4-2.0, p < .0001) more likely to endorse sipping alcohol by ages 9-10, while youth with low-level doses of alcohol throughout the entire pregnancy were 2.9 times (95 % CI 1.9-4.6, p < .0001) more likely to endorse sipping, when adjusting for confounding factors. A dose-dependent association between total standard drinks consumed during pregnancy and youth sipping endorsement was observed (β = 0.2, 95 % CI 0.1-0.2, p < .0001).Conclusions: This study shows that any alcohol use during pregnancy may play an important role in very early alcohol use experimentation among offspring by ages 9-10. [ABSTRACT FROM AUTHOR]