Addiction

Aims To estimate the prevalence of past-year smoking quit attempts in Great Britain and examine variation by sociodemographic and socioeconomic characteristics, mental health, alcohol use, smoking-related characteristics, and geographic area. Design Cross-sectional analysis of data from a nationally representative household survey (the Smoking Toolkit Study) conducted October 2020 to May 2026. Setting Great Britain. Participants 24,786 adults ([≥]18y) who reported past-year tobacco smoking. Measurements The outcome was self-reporting having made at least one serious attempt to stop smoking in the previous 12 months. Associations with age, gender, ethnicity, social grade, health-related economic inactivity, mental health conditions, psychological distress, alcohol consumption, use of non-combustible nicotine, cigarette type and consumption, strength of urges to smoke, and motivation to stop smoking were assessed. We calculated weighted prevalence estimates and odds ratios (ORs) adjusted for survey year. Findings Overall, 36.7% [95%CI=36.0-37.4] of adults who had smoked in the past year self-reported making at least one quit attempt. Annual prevalence was relatively stable over the study period (range: 35.5% [33.9-37.1] to 37.6% [35.9-39.3]). Making a past-year quit attempt was more common among younger adults (48.0% among 18-24-year-olds) and declined progressively with age (24.6% among [≥]65-year-olds; OR=0.35, 95%CI=0.31-0.39). Compared with White adults, making a past-year quit attempt was more common among Black (OR=1.31, 1.11-1.55) and Asian (OR=1.40, 1.21-1.62) adults. Adults with a history of diagnosed mental health conditions (OR=1.27, 1.17-1.38) and moderate (OR=1.31, 1.20-1.43) or severe psychological distress in the past month (OR=1.39, 1.25-1.56) had greater odds of reporting a past-year quit attempt than those without. Those reporting increasing/higher risk alcohol consumption had lower odds than non-drinkers (OR=0.88, 0.82-0.95). Current use of nicotine replacement therapy (OR=2.59, 2.36-2.83) and vapes (OR=2.15, 2.02-2.30) were positively associated with reporting a past-year quit attempt. Odds were lower among those with greater cigarette consumption (OR range 0.79-0.86 among those smoking >10 vs. [≤]5 cigarettes per day). Motivation to stop smoking showed the strongest gradient (OR range 2.95-29.09). Geographic differences were modest, with prevalence ranging from 32.1% [29.9-34.3] in Wales to 39.4% [35.9-43.1] in North East England. Conclusions Between 2020 and 2026, around one in three adults in Great Britain who smoked in the past year reported making a serious attempt to quit, corresponding to approximately 3.5 million people annually. Making a past-year quit attempt was more strongly associated with smoking-related factors than sociodemographic characteristics.

Background: Loneliness and social isolation may contribute to tobacco and nicotine use, but existing studies have been inconsistent. This systematic review and meta-analysis examined these associations among adults amid the evolving nicotine product landscape. Methods: A systematic search of PubMed, MEDLINE, PsycINFO, and CINAHL identified peer-reviewed quantitative studies published between 2014 and 2025 searched in February-April 2026. Eligible studies included adults aged [≥]18 years examining loneliness and/or social isolation in relation to smoking or nicotine use. Two reviewers independently screened studies, extracted data, and assessed risk of bias (using the National Heart, Lung, and Blood Institute risk of bias tool). Random effects meta-analyses were conducted to estimate pooled odds ratio (OR) with 95% confidence intervals (CIs). Results: 22 studies involving 273,954 participants met inclusion criteria, and 14 studies were included in the meta-analysis. A majority of the studies had low risk of bias. Meta-analysis findings showed that social isolation or loneliness was associated with significantly higher odds of nicotine product use (OR 1.84, 95% CI 1.48-2.29). Although no statistically significant association of nicotine product use and social isolation or loneliness (OR 1.35, 95% CI 0.72-2.53), some studies suggested bidirectional relationships, with smoking contributing to reduced social support and greater isolation over time. Sensitivity analysis showed the robustness of the meta-analysis findings. Subgroup analysis found no statistically significant differences were seen between subgroups defined by type of nicotine product, age groups, social isolation vs loneliness, measures of nicotine use behaviours and pre- vs post- COVID-19 pandemic period in the meta-regression. Limitations of included studies and analysis are discussed. Conclusions: Loneliness and social isolation are significant psychosocial correlates of nicotine product use. Cessation interventions may benefit from integrating social support and mental health strategies alongside traditional nicotine dependence treatment.

Background and Aims: Anxiety remains prevalent among adolescents while tobacco and nicotine product use, especially the recent increases of novel product use such as e-cigarettes and nicotine pouches, raises further public health concerns. The associations between novel tobacco and nicotine product use and anxiety remains understudied. This study aims to determine whether tobacco and nicotine product use is associated with generalised anxiety and whether this association differs by used product. Design: Cross-sectional survey, School Health Promotion study in 2025. Setting: A school-based nationwide survey conducted in all Finnish lower and upper secondary schools. Participants: Students aged 13-20 years in three school levels: 8.-9. grade students in lower secondary schools (N= 94 743, 73% of the students), 1st and 2nd-year students in general upper secondary schools (n=47 248, 70% of the students) and of vocational institutions (n=24 998, 38% of the students). Measurements: Exclusive (single product) and non-exclusive ([≥]1 products) daily or weekly use of tobacco and nicotine products, including nicotine pouches, e-cigarettes, cigarettes, and smokeless tobacco (snus). Generalised anxiety was measured using the Generalised Anxiety Disorder Scale (GAD-7). The cut-off of >10 points indicated participants with moderate to severe self-reported generalised anxiety symptoms. Background variables included sociodemographic variables and heavy drinking. Results: Of the 166,989 participants 51.4% were females, mean age was 15.7 (SD 1.27), 21.2% reported generalised anxiety. Prevalence of generalised anxiety increased gradient-wise in accordance with both non-exclusive and exclusive use frequency of different tobacco and nicotine products, as well as with number of products used. Daily use of nicotine pouches was associated with higher odds of anxiety compared with never use (boys: adjusted odds ratios (aOR) 1.19, 95% CI, 1.05 to 1.34; girls: aOR 1.74, 95% CI, 1.58 to 1.91), yet the association between daily e-cigarette use seemed to be stronger (boys aOR 1.96, 95% CI, 1.54 to 2.49; girls: aOR 2.29, 95% CI, 2.09 to 2.51). Summary: Any use of tobacco and nicotine products, including new products, is associated with generalised anxiety among adolescents, with some differences between products. Measures to prevent the initiation of tobacco and nicotine product use and to promote mental health among adolescents should be enacted.

Quantifying decision-making in experimental settings that mimic real-world conditions may provide insights into mechanisms underlying addiction. This study developed a computational model of opioid-seeking behavior. Out-of-treatment persons who regularly used heroin were stabilized on buprenorphine 8mg/day to minimize opioid withdrawal. Across programmatically-linked studies, three experimental conditions presented differing money vs. opioid unit amounts that could be earned per trial ($2 vs. 1-mg hydromorphone, n=23; $2 vs. 2-mg hydromorphone, n=36; $4 vs. 2-mg hydromorphone, n=24), controlling other factors. Progressive ratio schedules on each choice option required increasing effort across trials to earn the same amount. Trial-level outcomes were decision latency and choice on each option, and session-level outcomes were drug-money latency and breakpoint difference scores. A Markov computational model was used to predict the probability of choosing the same option as the previous trial (vs. switching). Model inputs included effort discrepancy (between earning the same vs. other commodity on next choice) and logarithm of the ratio of decisional speed (current vs. previous choice). Participants who more rapidly chose hydromorphone vs. money made more consecutive drug choices and expended greater effort earning hydromorphone. First-trial hydromorphone choice predicted continued effortful opioid-seeking. Participants repeated choices on 80% of trials; the model accurately predicted stick vs. switch behavior on 93% of trials. Participants typically repeated choices when faced with lower effort discrepancies and higher hydromorphone dose (2-mg vs. 1-mg). In conclusion, a Markov computational model accurately predicted effortful behavior in a choice paradigm that mimics real-world decisions between opioid and nondrug reinforcers.

Food addiction (FA) has been proposed as a phenotype sharing features with substance use disorders. Despite increasing recognition of food addiction as a behavioral phenotype with features overlapping substance use disorders, little is known about its prevalence or clinical significance among individuals with alcohol use disorder (AUD). Objective: To examine the prevalence of FA and to evaluate demographic, psychological, and alcohol-related correlates in individuals with AUD. Design, Setting, and Participants: This cross-sectional analysis included 743 adults with AUD who were either treatment seeking (Tx) (n = 534) for AUD and were enrolled in an inpatient program at the National Institutes of Health Clinical Center or not treatment-seeking (non Tx) (n = 209). Main Outcomes and Measures: FA symptoms were assessed using the Yale Food Addiction Scale, with >=2 symptoms categorized as FA in this report. Multivariable logistic regression models adjusted for age, education, and income were conducted separately within each cohort. Results: Among 743 adults with AUD, 238 (32.1%) met criteria for FA symptoms, with similar prevalence among Tx (32.6%) and nonTx (30.6%) participants despite marked differences in clinical characteristics. Across both cohorts, FA was independently associated with higher body mass index, greater psychological distress, and greater alcohol dependence severity. Childhood trauma and poorer sleep quality were additionally associated with FA among treatment-seeking participants, whereas alcohol-related measures differed according to treatment status. Conclusions and Relevance: FA was common among adults with AUD and was associated with greater psychological, behavioral, and metabolic burden regardless of treatment-seeking status. These findings suggest that FA identifies a clinically meaningful subgroup of individuals with AUD who may benefit from more comprehensive assessment and integrated treatment approaches.

Aims: To evaluate whether Cue-Induced Retrieval and Reconsolidation with Episodic Future Thinking (CIREF), which combines personalized drug-cue retrieval with structured future-oriented processing, produces greater changes in craving and delay discounting than a recent-past episodic active control in individuals with opioid use disorder receiving methadone maintenance treatment. Design: Multicentre, two-arm, parallel-group randomized controlled pilot trial with per-protocol analyses. Setting: Two outpatient addiction treatment and rehabilitation centres in Tehran, Iran. Participants: Thirty participants with opioid use disorder receiving methadone maintenance treatment were randomized to CIREF or Episodic Recent Thinking (ERT; n = 15 per group). Twenty-eight completed the intervention and were included in the analyses (n = 14 per group). Intervention and comparator: Participants completed one screening, baseline, and personalized cue-development session followed by three 75-minute intervention sessions. CIREF combined personalized drug-cue retrieval with future-oriented simulation, prediction, intention, and planning. ERT was structurally matched but anchored episodic processing to the recent past. Measurements: Primary craving outcomes comprised the three Desire for Drug Questionnaire (DDQ) subscales assessing session-level phasic/current craving immediately before and after each intervention session and the four Obsessive-Compulsive Drug Use Scale (OCDUS) subscales assessing tonic craving before and after the intervention period. The secondary outcome was Monetary Choice Questionnaire (MCQ) log(k), with more negative values indicating less steep delay discounting. Findings: After Holm correction across the three DDQ subscales, Group x Occasion interactions indicated greater reductions with CIREF for Desire and Intention to Drug Use, FGG(1.23, 32.09) = 24.37, pHolm < .001, partial eta-squared = .484, and Negative Reinforcement, FGG(1.35, 35.23) = 17.67, pHolm < .001, partial eta-squared = .405, but not Drug Abuse Control (pHolm = .172). After Holm correction across the four OCDUS subscales, only Desire and Mental Preoccupation with Drugs showed a significant Group x Time interaction, F(1, 26) = 12.35, pHolm = .007, partial eta-squared = .322; the remaining subscales were not significant (adjusted ps >= .177). MCQ log(k) showed a Group x Time interaction, F(1, 26) = 7.18, p = .013, partial eta-squared = .217; mean log(k) changed from -1.22 (0.36) to -1.80 (0.55) in CIREF and from -1.39 (0.32) to -1.44 (0.44) in ERT. Conclusions: In this small pilot sample, the future-oriented retrieval-based intervention produced greater changes than the recent-past active control in two dimensions of session-level phasic craving, one dimension of tonic craving, and monetary delay discounting. The results are preliminary and do not establish memory reconsolidation or effects on relapse or longer-term clinical outcomes.

Background Alcohol-associated injury is a leading cause of emergency department (ED) utilization in the United States and a clinically important driver of preventable morbidity across the adult lifespan. Prior surveillance research has characterized how the rate and severity of alcohol-associated injury vary by patient age, but whether the seasonal timing of injury risk is equally predictable across age groups (a question directly relevant to the timing of clinical screening intensification and public health intervention) has not been formally tested. Methods We conducted a retrospective surveillance analysis of 45,876 alcohol-associated ED visits among adults aged 18 years and older, identified from the National Electronic Injury Surveillance System (NEISS), 2019-2025 (weighted national estimate: 2,092,319 visits), using the structured Alcohol_Involved indicator introduced into NEISS case abstraction in 2019. Patients were stratified by sex and five age groups (18-24, 25-34, 35-49, 50-64, and [&ge;]65 years). Single-harmonic cosinor (Poisson) regression was used to estimate the seasonal peak day of injury risk (acrophase) for each stratum. To assess reliability, we performed leave-one-year-out jackknife resampling (seven iterations per group), case-resampling bootstrap confidence intervals (1,000 iterations), and likelihood-ratio tests of seasonal-phase interactions. Results Peak injury timing differed significantly across age groups (X^2 [8] = 2356.2, p < .0001). Adults aged 25-64 years showed a highly reproducible early-to-mid-July peak, with jackknife estimates shifting [&le;]14 days when any single study year was excluded. Adults aged [&ge;]65 years showed significant seasonal variation annually (all p < .0001, amplitude comparable to younger groups) but a pooled peak estimate that shifted by up to 100 days across jackknife iterations. Sex-stratified analyses revealed that this instability was driven entirely by females aged [&ge;]65 years (jackknife range: 332 days, peak consistently in late October through early January) rather than males aged [&ge;]65 (jackknife range: 31 days, peak consistently in early August). Hospital admission rates increased monotonically with age from 9.0% (18-24 years) to 31.8% ([&ge;]65 years). Conclusions Alcohol-associated injury follows a reproducible, calendar-stable summer seasonal pattern in adults aged 25-64 years. Among adults [&ge;]65 years, the previously reported temporal instability is concentrated in the female subgroup, whose seasonal injury risk does not converge on a fixed calendar window. These findings suggest that fixed-calendar prevention and screening strategies are well suited to working-age adults and older men, but older women may require a year-round, individually tailored approach. Keywords: Alcohol-related injury; Emergency department; Seasonality; Age factors; Sex differences; Injury surveillance; Cosinor analysis; Older adults

Objectives: Tobacco and cannabis co-use is common, and reductions in one substance may theoretically lead to compensatory increases in the other. This secondary analysis examined whether cannabis cue-induced dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation (DLPFC-rTMS) affects tobacco consumption among tobacco-using individuals with cannabis use disorder (CUD). Methods: Data were analyzed from a randomized, sham-controlled trial of DLPFC-rTMS for CUD. Participants were treatment-seeking adults with moderate or severe CUD who reported baseline tobacco use. Active or sham 10-Hz DLPFC-rTMS was delivered during cannabis cue exposure over 10 treatment visits. Linear mixed-effects models examined group differences in weekly percentage change from baseline in tobacco consumption over treatment and follow-up, adjusting for baseline tobacco consumption. Additional models examined whether changes in cannabis use were associated with changes in tobacco use. Results: Twenty participants were included, with 10 assigned to active rTMS and 10 to sham. Active rTMS was associated with a greater reduction in tobacco consumption than sham at 1-week post-treatment (t = -2.49, p = 0.015). Changes in cannabis use were not significantly associated with group differences in tobacco reduction. Estimated group differences did not indicate compensatory increases in tobacco use among participants with larger reductions in cannabis use. Conclusions: Cannabis cue-induced DLPFC-rTMS was associated with a short-term reduction in tobacco consumption relative to sham among tobacco-using individuals with CUD. These preliminary findings suggest possible cross-substance effects of DLPFC-rTMS and did not indicate compensatory tobacco increases. Larger trials specifically designed for cannabis-tobacco co-use are warranted.

Adolescent substance use is a major public health concern due to increased risk of future physical and mental health conditions. Fronto-striatal functioning - particularly regarding inhibition and reward processing - may increase vulnerability to high-risk substance use. However, it remains unclear if these neurobiological differences precede substance use or are consequences of it. The ongoing Adolescent Brain Cognitive Development (ABCD) Study follows over 10000 youth, offering an unprecedented opportunity to longitudinally examine substance use patterns throughout development. We utilized family-clustered time-varying Cox proportional hazard models to prospectively examine main and interaction effects of right Inferior Frontal Gyrus (IFG) inhibitory control and bilateral nucleus accumbens (NAc) reward response, alongside early life adversity and peer substance use as predictors of alcohol and cannabis onset in the ABCD Study. We identified a significant crossover interaction such that left NAc activity had a slight positive association with first full alcoholic drink in the context of higher right IFG activity but a negative association in the context of lower right IFG activity. However, peer alcohol and cannabis use emerged as the strongest predictors of outcomes. Alcohol onset was also more common in females, and early life adversity was associated only with cannabis onset. Findings indicate that interactions between inhibition- and reward-related brain regions may impact risk for early substance use onset, but these effects may be modest relative to socioenvironmental factors. Additionally, divergent alcohol and cannabis findings suggest that risk profiles are substance specific. Peer-focused strategies should be considered in preventive efforts.

A body of research suggests that autistic individuals are less likely to drink alcohol than neurotypicals. However, emerging studies support a link between autism and alcohol use. This complex relationship is also reflected in studies that have examined the genetic overlap between the two traits. However, it is unclear whether there is a direct causal relationship between them. To explore this, we applied a combination of polygenic score and Mendelian randomisation analyses using publicly available genome-wide summary statistics and phenotypic measures of autism and alcohol consumption from UK Biobank. LD score regression analyses did not provide evidence of a genetic correlation between genetic liability for autism and drinks consumed per week (rg=-0.08; CI95%=-0.19, 0.03). Further, findings from polygenic score analyses did not support an association between genetic liability for autism and overall monthly alcohol intake. Univariable Mendelian randomisation analyses showed little evidence for a total effect of autism, attention deficit hyperactivity disorder (ADHD) or depression on overall monthly alcohol consumption. Multivariable Mendelian randomisation analyses also showed little evidence of a direct effect of autism on drinks per week when controlling for ADHD and depression. It is plausible that genetic liability for autism does not directly increase the amount of alcohol consumed but instead operates via commonly co-occurring difficulties in the autistic community. However, our findings may be due to methodological shortcomings, including weak instruments biasing effects towards to the null. Consequently, results should be interpreted with caution and further research conducted to address these issues.

Introduction: Risk of recurrent opioid use during buprenorphine-naloxone (bup-nx) treatment is dynamic and remains elevated after initiation, with vulnerability shaped in part by treatment intensity and gaps between visits, yet routine outpatient care relies on episodic encounters and retrospective data. This mismatch can delay recognition of emerging instability and limit timely treatment adjustments. This paper reports the development and specification of an intervention strategy to address this mismatch. Methods: We used a structured, multi-phase design process to specify and configure a measurement-based care (MBC) strategy for bup-nx treatment (Bup-MBC) in outpatient addiction clinics through three phases: (1) a systematic review of patient-reported outcome measures (PROMs) for substance use treatment; (2) a qualitative needs assessment using the Theoretical Domains Framework and COM-B (Capability, Opportunity, Motivation-Behavior) model to identify gaps in risk monitoring, agency, and trust; and (3) iterative co-design with multidisciplinary clinicians to refine workflow fit and trust-preserving use of data. Patients informed item and feedback content during the needs assessment but did not participate in the co-design cycles. Results: Bup-MBC integrates (1) brief between-visit PROMs (e.g., withdrawal, craving, adherence); (2) immediate non-punitive patient feedback; (3) clinician-facing summaries and non-directive prompts in the electronic health record (EHR); and (4) an opt-in between-visit outreach pathway with predefined safety triggers, all configured within existing EHR and patient portal infrastructure. It targets patient and clinician capability to recognize changes in risk, opportunity for action through structured monitoring and visit preparation, and trust and agency through non-punitive communication, without adding substantial burden. The full measure set, severity bands, and question-to-action map are provided as supplementary material. Key trade-offs included prioritizing single-item measures for feasibility, balancing opt-in outreach with safety overrides, and assuming routine clinician use of summaries. Conclusion: This development study specifies an EHR-integrated MBC strategy for outpatient bup-nx treatment. As single-center design work with co-design limited to clinicians and delivery contingent on portal or text-message access, its outputs are hypotheses about mechanism and fit rather than demonstrated effects. Feasibility studies are needed to evaluate uptake, acceptability, workflow fit, and effects on treatment.

BackgroundObservational comparisons of former smokers who use non-combusted nicotine products with former smokers who quit without them require that two quantities be measured precisely: which product is being used, and how long ago cigarette smoking stopped. Neither quantity is recorded by the National Health Insurance Service (NHIS) screening instrument used in a recent Korean cohort study of post-cessation e-cigarette use and lung cancer risk. We characterized both quantities in a contemporaneous, nationally representative survey of the same population. MethodsWe analyzed the public-release microdata of the Korea National Health and Nutrition Examination Survey (KNHANES), 2018 to 2023, restricted to adults aged 19 years and older. Former smokers were identified by smoking status, and cessation duration was taken from the item recording months since the last cigarette. Former smokers currently using a heated tobacco product (HTP) or an e-cigarette (EC) were compared with former smokers using neither. KNHANES 2018 asked a generic e-cigarette question and, separately, a checklist naming HTP brands, allowing the two product classes to be separated. Distributions were compared with rank-based methods, the age-duration relationship with Theil-Sen regression, and residual imbalance by restricting the comparison group to respondents age-matched to within two years. ResultsThe 2018 analytic sample comprised 1,348 former smokers, of whom 43 currently used HTP or EC and 1,305 used neither. Among the product-using former smokers, 58% reported HTP use without e-cigarette use, 21% reported both, and 21% reported e-cigarette use without HTP use; 79% reported any HTP use. Median cessation duration was 0.7 years (IQR 0.25 to 1.5) among product users and 12.0 years (IQR 5.0 to 20.0) among those using neither (Kolmogorov- Smirnov D = 0.76, P < 0.001), with the product user having quit more recently in 92% of cross-group pairs. The separation persisted within the short-term (<5 year) stratum (D = 0.34, P < 0.001; 73% of pairs) and after age matching, where the residual gap was 9.3 years. Cessation duration rose with age among those using no product (Theil-Sen slope +0.30 years per year) but was flat among product users (-0.01). Restricting to the screening-eligible stratum used in the cohorts high-risk analysis did not attenuate the imbalance: among those aged 50 to 80, median cessation among no-product quitters rose to 15.5 years (n = 858), and adding a 20 pack-year criterion left 421 no-product quitters with a median of 11.0 years against three HTP/EC users who had quit 0.25, 1.0 and 2.0 years earlier, despite closely matched cumulative exposure (mean 37.6 vs 37.7 pack-years). The overall contrast reproduced in every wave from 2018 to 2023, with an age-matched residual of 9 to 11 years. ConclusionsIn a nationally representative survey of the same population and the same calendar year as the NHIS screening cohort analyzed by Kim et al., Korean former smokers using non-combusted nicotine products differed from other former smokers in two respects that bear directly on how such comparisons should be read. First, they were predominantly HTP users: 79% reported any HTP use, and only 21% reported e-cigarette use without HTP use. Second, they had stopped smoking approximately a decade more recently, a difference that survived stratification at five years and exact age matching. Neither quantity is recorded in the NHIS screening instrument. Cohort estimates comparing post-cessation product users with other quitters should therefore be interpreted with caution if they do not precisely characterize product composition and to time since cessation, and future studies should measure both directly.

Background Oral contraceptive (OC) use, particularly during adolescence, may increase depression risk in some individuals, but it remains unclear who is susceptible to mood-related side effects and who is not. We aimed to detect single nucleotide polymorphisms (SNPs) and genes that moderate the effect of OC use on depression in young adulthood using data from the UK Biobank. Methods N=202,243 participants were followed from birth to age 23.29 (SD: 2.58) years. We used Cox models for counting processes to test the association between OC use and incident depression in young adulthood, and conducted a genome-wide-by-drug-interaction study (GWDIS) of SNP by OC use interactions alongside a standard genome-wide association study (GWAS) on incident depression in young adulthood. Results Over half of all participants (57.5%) initiated OC and 1.0% received a depression diagnosis during follow up. OC initiators had a 20% higher hazard of incident depression than non-initiators (HR=1.20, 95% CI=1.04-1.37). No SNPs reached genome-wide significance in the GWDIS, though eight showed suggestive interaction signals (p<1e-5). At the gene level, FSIP1 (p=5.90e-5) and EHBP1 (p=6.47e-5) showed suggestive signals, but none passed the genome-wide threshold. No SNPs reached genome-wide significance in the GWAS. Conclusions We did not find evidence for genetic variants that moderate the association between OC initiation and depression. If such effects exist, they are likely to be small and polygenic, suggesting there is currently no solid basis for using genetic data for individualised contraception counselling concerning mood-based side effects.

Background Alcohol is a leading modifiable risk factor for non-communicable disease. Zambia's National Alcohol Policy and the World Health Organization's target of a 10% relative reduction in the harmful use of alcohol both require that the trend be monitored. Alcohol items appear in four rounds of the Zambia Demographic and Health Survey (ZDHS), and those rounds are widely treated as a trend series, although whether they are one has never been tested. Methods Secondary analysis of ZDHS 2007, 2013-14, 2018 and 2024 (women aged 15-49, men aged 15-59). A direct current-use item is available in three rounds, with three different instruments for men and two for women. Four identification strategies were applied in ascending order of assumption: nesting bounds, which exploit the fact that a seven-day window falls within a thirty-day window and that within undated current status; restriction to the fieldwork months common to both rounds; a lifetime-use analogue available in 2024; and an instrument-constant partner-report series available in all four rounds, validated by linking each woman to her co-resident husband. Estimation throughout was design-based. Results The conventional series suggests a fall in current drinking among men from 42.0% (95% CI 39.9-44.1) in 2007 to 28.2% (95% CI 27.0-29.3) in 2024, and among women from 11.1% (95% CI 9.9-12.4) to 8.8% (95% CI 8.0-9.6). Neither change is sign-identified. Placed on a common thirty-day basis with matched fieldwork months, the 2013-14 to 2024 change lies between -7.6 and +1.2 percentage points for men and between -0.2 and +3.7 for women. The instrument-constant proxy fell from 53.7% in 2007 to 37.7% in 2018, then plateaued at 37.0% in 2024; a constant-decline model is rejected (Q = 15.9, 2 df, p = 0.0003). Sensitivity of the proxy against husbands' own reports fell from 86.0% to 66.8%. The 2024 cross-section is unaffected and is reported in full. Conclusions These data do not establish the apparent national decline in alcohol use. Differences in reported prevalence across ZDHS rounds substantially reflect instrument change, reference-period shift, fieldwork seasonality and decay in proxy reporting. On present evidence Zambia cannot monitor its alcohol commitments from national survey data. Trend monitoring would require a consistent alcohol module restored to the questionnaire, an occasion-based heavy-drinking item, and the reporting of fieldwork month.

Objectives Outpatient buprenorphine-naltrexone (bup-nx) treatment reduces overdose risk, yet many patients still return to use or disengage from treatment. We sought to understand how patients and prescribers experience and manage relapse risk, monitoring, and treatment agency in routine bup-nx treatment to identify gaps in current practice. Methods We conducted a qualitative needs assessment using semi structured, critical incident interviews with patients receiving outpatient bup-nx and prescribers who manage bup-nx treatment. Interviews examined situations involving relapse risk and empowerment in treatment decisions. We structured data collection and analysis using the Theoretical Domains Framework and COM B model to characterize determinants. Transcripts were coded deductively and inductively until code level saturation was reached. Results Participants (9 patients, 8 prescribers) described nine treatment needs mapped to the Capability, Opportunity, and Motivation components of the COM B model. These themes highlighted how patient agency in bup-nx treatment was constrained by physiologic and emotional states, with withdrawal, craving, pain, and distress often overriding longer term goals. Relapse vulnerability was experienced as dynamic and intensifying between visits, while clinical detection remained anchored to visit bound assessments, urine drug testing, refill patterns, and crisis driven contact, creating blind spots. Structural friction (pharmacy rules, insurance disruptions, transportation and housing instability), stigma from family and recovery communities, and motivational processes tied to fluctuating readiness and trust in monitoring further shaped engagement, disclosure, and dosing decisions; the same monitoring tools could either support honest disclosure or provoke concealment when perceived as punitive. Conclusions Relapse risk and agency in bup-nx treatment are negotiated as dynamic processes within structurally constrained and trust sensitive systems. Addressing the identified capability, opportunity, and motivation gaps will require patient centered, trust preserving approaches to monitoring and shared decision making.

Autistic individuals may be at an increased risk of hazardous drinking compared to non-autistic counterparts: potential motivations include facilitated social interactions and self-medication of co-occurring difficulties, and possible risk factors include being older and female. However, research remains limited and centred around clinical samples. Given the diversity of the autistic community, it is important to understand the intricacies of alcohol use to inform appropriate support. Eighteen autistic adults took part in semi-structured interviews about their drinking experiences. Data were analysed using reflexive thematic analysis. Three main themes were created (Autistic experiences, Managing expectations and coping by drinking and Recommendations for support). Autistic experiences was used to denote the ways in which participants described their own autistic features influenced their relationship with alcohol. Managing expectations and coping by drinking was chosen to reflect the pressures felt by participants to show up in social relationships and the co-occurring difficulties many of them managed using alcohol. Therapeutic preferences for alcohol services were captured under Recommendations for support. As expected, participants used alcohol to facilitate social interactions and self-medicate. However, additional nuances uncovered may provide clinical utility and highlight the need for further research in other demographics within the community.

Introduction: Self-rated health is an important patient-centred measure of health. The relationship between cannabis use and self-rated health has been previously studied, although with methodologic concerns which we aimed to address in this investigation. Methods: Propensity score weighted analyses of the National Health and Nutrition Examination Survey (NHANES) 2009-2018 were conducted. The primary exposure was self-reported cannabis use in the 30 days prior to survey response. The primary outcome was self-rated health measured on a five-level ordinal scale. Secondary outcomes included the number of days in the past months with: i) poor physical health, ii) poor mental health, and iii) activity limitations related to poor health. A weighted proportional odds regression model was used for the primary analysis and weighted zero-inflated negative binomial regression models were used for each secondary analysis. Results: Among 22,055 adults aged 20-59 responding to the NHANES cannabis questionnaire, 14.4% endorsed use in the past 30 days. After reweighting the sample to balance cannabis users and non-users across sociodemographic, medical, and lifestyle characteristics, there was no statistically significant association between recent cannabis use and higher levels of self-rated health (OR 0.90, 95% CI 0.80-1.01). Cannabis use was associated with poor mental health and activity limitations in the past month, but not poor physical health. Conclusions: Recent cannabis use was not associated with self-rated health but was associated with poor mental health and activity limitations in the past month. Cannabis users at risk of poor mental health should be connected with clinicians to help guide therapy.

Background: As cannabis policy changes in the United States, secondhand cannabis smoke (SCS) is increasingly common, including within families. However, prevalence of exposure and clinical correlates over time in adolescents are not fully understood. Objectives: (1) To estimate the prevalence of SCS and personal cannabis use in US-based teens exposed to SCS, and (2) examine the cognitive trajectories of adolescents exposed to SCS compared to non-exposed peers. Methods: Data from the Adolescent Brain Cognitive Development (ABCD) Study was used. Participants (n=11,316 of full cohort with follow-up data; n=776 with self-reported family SCS exposure) attended yearly visits from ages 11-17, completing substance use interviews, toxicological testing, and the NIH Toolbox Cognitive battery. Youth with SCS but no personal cannabis use (n=419; 47% female) were matched on prenatal substance exposure, family substance use history, and sociodemographics to non-SCS exposed and non-cannabis-using youth with a 1:2 ratio (Controls n=838). Linear mixed-effects models assessed cognitive performance by SCS*age interactions, accounting for random effects of subject and family. Covariates included sex and alcohol, nicotine, and other substance use. Secondary models analyzed performance by cumulative waves of reported SCS exposure interacting with age. Results: Of the full cohort, 6.9% (n=776) reported exposure to SCS. Of these individuals, 46% endorsed lifetime personal cannabis use by age 17, relative to 20% of non-SCS exposed youth (OR=3.83[95%CI:3.29,4.44]). Within matched participants, SCS*age demonstrated a significant interaction on attention and inhibitory control ({beta}=-0.32, p=.028), with SCS demonstrating reduced improvement over time. More waves of exposure were also associated with worse performance over time ({beta}=-0.39, p=.057). Discussion: Almost half of those who had been exposed to SCS endorsed personal cannabis use. Cognitive findings were domain specific, similar to findings in secondhand tobacco: SCS exposed youth showed restricted improvement in attention and inhibitory control by age 17. Public health and policymakers should make efforts to curb youth SCS exposure, given the potential for risk which has not been fully explored to date.

Background The detrimental impact of alcohol consumption on the gut microbiome is well-established. However, less is known about how alcohol exposure during pregnancy affects the maternal gut and vaginal microbiota, or how these microbial changes relate to subsequent infant diagnosis of fetal alcohol spectrum disorder (FASD). We therefore investigated associations between self-reported alcohol use during pregnancy, infant FASD diagnosis, and maternal gut and vaginal microbiota. Methods Fecal samples (n = 207) and vaginal swabs (n = 28) from pregnant participants recruited through antenatal clinics in the Western Cape Province of South Africa were profiled by 16S rRNA V1-V2 amplicon sequencing. Maternal alcohol use was assessed using Alcohol Use Disorder Identification Test (AUDIT) scores, and FASD was diagnosed in infants using revised Institute of Medicine criteria. Microbial diversity, taxonomic profiles and PICRUSt2-predicted functional pathways were analyzed using vegan, phyloseq and MaAsLin3. Results Maternal AUDIT scores were negatively associated with maternal gut microbiota richness, Shannon, and Inverse Simpson diversity (p < 0.05). Observed richness was also reduced in participants whose infants were diagnosed with FASD (p = 0.046). Gut microbiota community structure was not significantly associated with alcohol use or infant FASD diagnosis. However, taxonomic and functional analysis suggested gram-positive taxa depletion with alcohol use and FASD diagnosis, and impaired one-carbon metabolism among participants with infants diagnosed with FASD. Vaginal microbiota diversity and composition were not associated with alcohol use or infant diagnosis. Conclusions This is the first human study to investigate the maternal gut and vaginal microbiota in relation to alcohol use during pregnancy and infant FASD outcomes. Our findings suggest that alcohol use is associated with maternal gut microbiota disruption, with potential implications for FASD development in exposed infants. Further investigation of alcohol-associated maternal microbial disturbances may inform microbiota-targeted strategies to improve maternal and infant health linked to alcohol use.

Studies of resemblance for disorders and other traits measured at the binary (yes/no) level between relatives frequently contain individuals who are currently in the negative category but who will become positive in future. For example, a 10-year-old may develop depression in the future, but is as yet unaffected. Such censoring can substantially bias estimates of correlation between relatives. To overcome this problem we develop a model for the association between liability to a disorder, and its age at onset. The model is designed for data from pairs of relatives to enable estimation of the correlation between an individuals' liability to disorder and their age at onset. Usually, such information is not available at the individual level, because age at onset is uniquely available when onset has occurred. Lacking variation in disorder status, data from non-related persons cannot estimate the covariance between liability and age at onset. Data from relatives can resolve this issue when there is a correlation in liability between the relatives, because different age at onset distributions would be expected in concordant vs. discordant pairs of relatives. Greater severity and worse outcomes are often observed among those with earlier onset, so a correlation between disorder liability and age at onset seems likely in many cases. In this article we present the basic theory of the model, implemented as a mixture distribution, and an application to cannabis use in a Virginia Twin Study of Adolescent Behavioral Development. A negative association of (-.212) between age at onset an liability was found, with confidence intervals of -.263 to -.152, which do not cross zero. The method contrasts with Cox Proportional Hazards, in which disorder liability and onset timing are treated as a single dimension.