Characterizing reward and relief/habit drinking profiles in a study of naltrexone, varenicline, and placebo.

INTRODUCTION: This study aims to clarify differences in mood, craving, and treatment response between reward and relief/habit individuals in a study of naltrexone, varenicline, and placebo. We hypothesized that relief/habit individuals would have a poorer mood during early abstinence and higher levels of alcohol craving than reward individuals. We hypothesized that reward individuals would demonstrate better drinking outcomes on naltrexone versus placebo. METHODS: Data were culled from a randomized, double-blind, placebo-controlled human trial of 53 individuals (18F/16M) with alcohol use disorder randomized to varenicline (n = 19), naltrexone (n = 15), or matched placebo (n = 19). In this 6-day practice quit trial, participants attempted to abstain from drinking and completed daily diaries. Participants were classified into reward or relief/habit subgroups based on self-reported motivation for drinking. Multilinear models tested differences in mood and alcohol craving between reward and relief/habit individuals. General linear models tested differences between reward and relief/habit individuals' drinking outcomes on each medication versus placebo. RESULTS: Relief/habit individuals showed decreases in positive mood and increases in negative mood over the quit attempt across medications, compared to reward individuals (P's < .05). Reward individuals' tension decreased on naltrexone, while relief/habit individuals' tension remained stable (F = 3.64, P = .03). Reward individuals in the placebo group had higher percent days abstinent than relief individuals in the placebo group (P < .001). DISCUSSION: This study suggests relief/habit individuals' mood worsens during early abstinence. Our finding that reward individuals' tension decreased on naltrexone and increased on placebo may suggest a clinical response to the medication.

Applying Social Network Theory to Vaping in High School: Implications for Person-Centered Intervention.

BACKGROUND: Peer influence on risky behavior is particularly potent in adolescence and varies by gender. Smoking prevention programs focused on peer-group leaders have shown great promise, and a social influence model has proven effective in understanding adult smoking networks but has not been applied to adolescent vaping until 2023. This work aims to apply a social influence model to analyze vaping by gender in a high school network. METHODS: A high school's student body was emailed an online survey asking for gender, age, grade level, vape status, and the names of three friends. Custom Java and MATLAB scripts were written to create a directed graph, compute centrality measures, and perform Fisher's exact tests to compare centrality measures by demographic variables and vape status. RESULTS: Of 192 students in the school, 102 students responded. Students who vape were in closer-knit friend groups than students who do not vape (p < .05). Compared to males who vape, females who vape had more social ties to other students who vape, exhibiting greater homophily (p < .01). Compared to females who do not vape, females who vape were in closer-knit friend groups (p < .05) and had more ties to other students who vape (p < .01). CONCLUSION: Differences in vaping by social connectedness and gender necessitate school and state policies incorporating the social aspect of vaping in public health initiatives. Large-scale research should determine if trends can be generalized across student bodies, and more granular studies should investigate differences in motivations and social influence by demographic variables to individualize cessation strategies.

Early life stress is associated with greater negative emotionality and peripheral inflammation in alcohol use disorder.

Early life stress (ELS) increases risk for psychiatric illness, including alcohol use disorder (AUD). Researchers have hypothesized that individuals with and without a history of ELS who have the same primary DSM-5 diagnosis are clinically and biologically distinct. While there is strong support for this hypothesis in the context of mood disorders, the hypothesis remains largely untested in the context of AUD. This study investigated the impact of ELS on the neuroclinical phenomenology and inflammatory profile of individuals with AUD. Treatment-seeking adults with AUD (N = 163) completed the Adverse Childhood Experiences (ACE) Questionnaire and phenotypic battery as part of a pharmacotherapy trial for AUD (NCT03594435). Participants were classified as having "no-ELS," (ACE = 0) "moderate-ELS," (ACE = 1, 2 or 3) or "high-ELS" (ACE = 4 + ). The Addictions Neuroclinical Assessment domains incentive salience and negative emotionality were derived and used to assess the neuroclinical phenomenology of AUD. We tested (1) cumulative ELS as a predictor of ANA domains and (2) ELS group differences in ANA domains. A subset of participants (N = 98) provided blood samples for a biomarker of peripheral inflammation (C-reactive protein; CRP); analyses were repeated with CRP as the outcome variable. Greater ELS predicted higher negative emotionality and elevated CRP, but not incentive salience. The high-ELS group exhibited greater negative emotionality compared with the no-ELS and moderate-ELS groups, with no difference between the latter two groups. The high-ELS group exhibited elevated CRP compared with the no/moderate-ELS group. Findings suggest that high-ELS exposure is associated with a unique AUD neuroclinical presentation marked by greater negative emotionality, and inflammatory profile characterized by elevated peripheral CRP.

A practice quit model to test early efficacy of medications for alcohol use disorder in a randomized clinical trial.

RATIONALE: Screening novel medications for alcohol use disorder (AUD) requires models that are both efficient and ecologically-valid. Ideally, such models would be associated with the outcomes of a given medication in clinical trials. OBJECTIVES: To test a novel human laboratory model in which individuals with intrinsic motivation to change their drinking engage in a "practice quit" attempt consisting of 6 days of complete abstinence from alcohol. METHOD: Individuals with current AUD completed a randomized, double-blind, placebo-controlled study of naltrexone (50 mg), varenicline (2 mg bid), or matched placebo. Participants were titrated onto the study medication for 1 week prior to starting the 6-day practice quit attempt. During the practice quit attempt, participants completed daily interviews with research staff. All participants completed an alcohol cue-exposure paradigm before starting the study medication and after 2 weeks of study medication. RESULTS: There were no significant medication effect on drinks per drinking day (F(2,49) = 0.66, p = 0.52) or percent days abstinent (F(2,49) = 0.14, p = 0.87) during the 6-day practice quit period. There were no medication effects on alcohol cue-reactivity (F(2,44) = 0.80, p = 0.46). Notably, participants sharply reduced their drinking during the entire 13-day medication treatment period, as compared to reducing only during the 6-day practice quit period. During the total medication period, higher levels of motivation to change was associated with higher percent days abstinent (F(1,49) = 8.12, p < 0.01). CONCLUSIONS: This study reports mostly null findings, which challenges us to decompose its nuanced design to consider model refinements. Possible changes to the model include considering the requirement for intrinsic motivation for change, including a longer practice quit period, encompassing the medication administration timeframe in the practice quit period, increasing the required sample size for signal detection, and examining a post COVID-19 pandemic cohort.

Age Specificity of Effects of Health Problems on Drinking Reduction: A Lifespan Developmental Analysis.

Older adult drinking poses a growing public health concern, especially given the ongoing aging of the United States population. As part of a larger lifespan developmental project contrasting predictors of drinking reductions across different periods of adulthood, we tested age differences in effects of health problems on drinking declines across young adulthood, midlife, and older adulthood. We predicted these effects to be developmentally specific to midlife and older adulthood. We also tested moderation by alcohol use disorder (AUD) symptomatology and by indices of sociodemographic disadvantage (sex and race/ethnicity). Analyses used data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), leveraging NESARC's vast age range (18-90 + ; N = 43,093) and two waves of longitudinal data. Multiple-group cross-lag models tested differences across age groups in cross-lag paths between health problems and alcohol consumption. As hypothesized, health problem effects on drinking reductions were developmentally specific to midlife and older adulthood. However, models testing moderation by AUD symptomatology showed that these adaptive effects of health problems on drinking reductions did not extend to those with one or more AUD symptoms. Little evidence was found for moderation by sex or race/ethnicity. Findings support the notion of health concerns as a pathway to drinking reduction that increases in importance across the adult lifespan. However, given the moderation by AUD symptoms, findings also highlight a need to understand barriers to health-related pathways to drinking reduction among relatively severe midlife and older adult drinkers. These findings hold implications for lifespan developmental tailoring of clinical, public health, and policy interventions.

A life span developmental investigation of marriage and problem-drinking reduction.

While prior literature has largely focused on marriage effects during young adulthood, it is less clear whether these effects are as strong in middle adulthood. Thus, we investigated age differences in marriage effects on problem-drinking reduction. We employed parallel analyses with two independent samples (analytic-sample Ns of 577 and 441, respectively). Both are high-risk samples by design, with about 50% of participants having a parent with lifetime alcohol use disorder. Both samples have been assessed longitudinally from early young adulthood to the mid-to-late 30s. Separate parallel analyses with these two samples allowed evaluation of the reproducibility of results. Growth models of problem drinking tested marriage as a time-varying predictor and thereby assessed age differences in marriage effects. For both samples, results consistently showed marriage effects to be strongest in early young adulthood and to decrease somewhat monotonically thereafter with age, reaching very small (and nonsignificant) magnitudes by the 30s. Results may reflect that role transitions like marriage have more impact on problem drinking in earlier versus later adulthood, thereby highlighting the importance of life span developmental research for understanding problem-drinking desistance. Our findings can inform intervention strategies aimed at reducing problem drinking by jumpstarting or amplifying natural processes of adult role adaptation.

Therapy Dose Mediates the Relationship Between Buprenorphine/Naloxone and Opioid Treatment Outcomes in Youth Receiving Medication for Opioid Use Disorder Treatment.

BACKGROUND: Evidence-based interventions for treating opioid use disorder (OUD) in youth are limited and little is known about specific and general mechanisms of OUD treatments and how they promote abstinence. METHODS: The present study used data from the NIDA-CTN-0010 trial to evaluate the mediating effects of psychosocial treatment-related variables (therapy dose and therapeutic alliance) on end-of-treatment opioid abstinence in a sample of youth with OUD (n = 152, 40% female, mean age = 19.7 years) randomized to receive either 12-weeks of treatment with Bup/Nal ("Bup-Nal") or up to 2 weeks of Bup/Nal detoxification ("Detox") with both treatment arms receiving weekly individual and group drug counseling ± family therapy. RESULTS: Participants in the Bup-Nal group attended more therapy sessions (16 vs 6 sessions), had increased therapeutic alliance at week-4, and had less opioid use by week-12 compared to those in the Detox group. In both treatment arms, youth who attended more therapy sessions were less likely to have a week-12 opioid positive urine. In a multiple mediator model, therapy dose mediated the association between treatment arm and opioid abstinence. CONCLUSIONS: These findings provide preliminary support for a "dose-response" effect of addiction-focused therapy on abstinence in youth OUD. Further, the results identified a mediating effect of therapy dose on the relationship between treatment assignment and opioid treatment outcomes, suggesting that extended Bup-Nal treatment may enhance abstinence, in part, through a mechanism of therapy facilitation, by increasing therapy dose during treatment.

Sex-based differences in psychiatric symptoms and opioid abstinence during buprenorphine/naloxone treatment in adolescents with opioid use disorders.

BACKGROUND: Recent studies indicate that sex-based differences exist in co-occurring psychiatric symptoms and disorders among individuals with opioid use disorders (OUD). Whether these associations are present in adolescent samples and change during OUD treatment is poorly understood. OBJECTIVES: In the current study, we examined sex-based differences in psychiatric symptoms and relationships among sex, psychiatric symptoms, and opioid use outcomes in youth with OUD receiving buprenorphine/naloxone (Bup/Nal) and psychosocial treatment. METHODS: The study randomly assigned one hundred and fifty-two youth (15-21 years old) diagnosed with OUD to either 12 weeks of treatment with Bup/Nal or up to 2 weeks of Bup/Nal detoxification with both treatment arms receiving weekly drug counseling as part of a multisite clinical trial (NIDA-CTN-0010). We compared psychiatric symptoms, assessed via the Youth Self Report (YSR) at baseline and week 12, across male and female OUD participants. The study used logistic regression models to identify sex and psychiatric symptom variables that were predictors of opioid positive urine (OPU) at week 12. RESULTS: Compared to males, females with OUD had higher mean psychiatric symptom scores at baseline across broad-band and narrow-band symptom domains. The study observed significant reductions in psychiatric symptom scores in both males and females during treatment, and by week 12, females only differed from males on anxious-depressive symptom scores. Females, in general, and youth of both sexes presenting to treatment with higher anxious depression scores were less likely to have a week-12 OPU. CONCLUSIONS: Clinically significant sex-based differences in psychiatric symptoms are present at baseline among youth with OUD receiving Bup/Nal-assisted treatment and mostly resolve during treatment.