Addiction

Background: Alcohol use disorder (AUD) is marked by high relapse rates often driven by craving, yet less is known about whether in vivo, social, and place-based alcohol cues are differentially associated with craving across affective states. This study examined independent and affect-contingent associations of these cues with momentary craving in adults with AUD enrolled in an alcohol intervention study. Methods: Thirty-three adults with AUD completed up to four daily ecological momentary assessments (EMA) for 28 days. EMA prompts assessed craving, in vivo alcohol exposure, being around usual drinking partners, being in usual drinking places, and high-arousal positive affect (PA) and negative affect (NA). Multilevel mixed-effects models adjusted for demographics, intervention phase (1 = post, 0 = pre), AUD severity, and temporal and contextual covariates. Results: EMA compliance was high (median per-participant = 86.6%). Within-person elevations in in vivo alcohol exposure and being around usual drinking partners were independently associated with greater momentary craving, whereas being in usual drinking places was not. In vivo alcohol exposure was more strongly associated with craving during higher-than-usual PA ({beta} = 0.08, p = .032), whereas being in usual drinking places was more strongly associated with craving during higher-than-usual NA ({beta} = 0.06, p = .036), adjusting for intervention phase, which was associated with lower craving. Conclusions: Findings support the need for personalized just-in-time adaptive interventions tailored to high-risk, momentary cue-affect contexts in AUD, beyond low-frequency clinician-delivered feedback that may reduce average craving but not fully address real-time risk. ClinicalTrials.gov registration: NCT05135767.

BackgroundFetal alcohol spectrum disorders (FASD) arising from prenatal alcohol exposure (PAE) are the leading preventable cause of neurobehavioral disorders. Early pregnancy is particularly vulnerable to ethanol toxicity, yet alcohol use often continues until pregnancy recognition. In Finland, national incidence estimates of PAE and FASD remain limited. ObjectiveTo estimate the incidence of any PAE and heavy PAE in Finland between 1990 and 2025, and to model the annual number of children with FASD born in or immigrating to Finland. MethodsWe developed a mathematical modelling framework integrating studies on alcohol use during pregnancy in Finland, biomarker-based estimates of heavy PAE, national population statistics, and international active case ascertainment studies on FASD prevalence. Incidence of any PAE was estimated from self-reported alcohol use, including pre-recognition exposure. Heavy PAE was estimated by combining binge-drinking prevalence, delayed pregnancy recognition, biomarker data and anonymous self-reports. FASD incidence was modelled using two approaches: 1) an international multiplier linking FASD prevalence to heavy episodic drinking prevalence among women, and 2) a conventional epidemiological ratio between any PAE and FASD. Immigration and international adoption were incorporated. ResultsSelf-reported alcohol use during pregnancy declined following abstinence recommendations in the early 2000s, while pre-recognition use remained relatively stable. Heavy PAE decreased from 9% (uncertainty range 7-11%) in the 1990s to 6% (4-8%) in the early 2020s. Any PAE declined from 75% (60-85%) to 32% (26-38%). Modelled FASD incidence showed similar decreasing trends, ranging from 6.8% to 5.6% (multiplier model), and from 6% to 3% (any PAE-based model). ConclusionPAE remains common in Finland, and the burden of FASD is substantial despite declining trends. Additional biomarker-based studies of PAE and active case ascertainment of FASD are needed to refine current estimates. Strengthened public health efforts to reduce PAE, including the efforts before recognition of pregnancy, are essential.

BackgroundPractical alcohol risk-reduction strategies are widely recommended in public-facing alcohol guidance, but randomized evidence from socially interactive drinking episodes remains limited. We conducted a pilot cluster randomized trial to evaluate the feasibility and preliminary effects of a package intervention comprising practical drinking-strategy information, participant self-selection of same-day strategies, and a brief commitment declaration in a social drinking laboratory. MethodsThis single-center, parallel-group pilot trial was conducted in Japan. Pre-existing social groups participated. One or two groups scheduled in the same session slot were combined into a time-slot allocation unit, which was randomized 1:1 either to the package intervention or to alcohol-related knowledge only. The primary outcome was total pure alcohol intake during the first 120 min. Session satisfaction on a Visual Analog Scale (VAS) was a prespecified secondary participant-experience outcome. ResultsOf 83 interested individuals, 63 were randomized and 59 participants in 17 social groups and 12 allocation units were included in the modified intention-to-treat analysis. The mean paired intervention-control difference for 120-min alcohol intake was-8.84 g (95% confidence interval [CI]-27.92 to 10.23; exact sign-flip p = 0.281). The corresponding exploratory 0-30 min difference was-4.90 g (95% CI-10.48 to 0.68; exact sign-flip p = 0.094). In a genotype-adjusted participant-level sensitivity analysis, the intervention coefficient for 120-min intake was-16.0 g (95% CI-30.9 to-1.1; p = 0.036). Session satisfaction was high in both arms with no clear between-arm difference. Next-day follow-up was 100%, and no adverse-event-related discontinuations occurred. ConclusionsThe intervention was feasible to deliver in a socially interactive drinking setting, and session satisfaction was high in both arms. Primary allocation-unit estimates favored lower alcohol intake but were imprecise. Larger trials are needed to estimate effects more precisely, while considering the potential influence of genotype imbalance on effect estimation in East Asian samples. Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) UMIN000060685. Registered 17 February 2026.

ObjectivesUptake of evidence-based smoking cessation support remains limited. Digital interventions offer the prospect of scalable and highly accessible support. Smoke Free, a digital mobile application using established behaviour change techniques, has shown promise, but no large-scale randomised controlled efficacy trial has yet been conducted. We assessed its effectiveness for smoking cessation. DesignIn this prospective, randomised, controlled, two-arm, parallel clinical trial with 6-month follow-up, study personnel and patients were blinded. SettingThe trial was conducted nationwide in Germany, utilising a decentralised, fully remote trial design. Enrolment took place digitally after receiving brief advice from a healthcare professional, following guidelines for primary care. ParticipantsOut of a volunteer sample of 1850 patients assessed for eligibility, 1466 adult cigarette smokers who had at least moderate cigarette dependence (F17.2, FTCD[&ge;]3) were recruited between August 2023 and February 2024; 84.1% (1233 participants) completed the primary outcome measure. InterventionsThe intervention group (IG) received the Smoke Free app including behaviour-change missions and gamification elements, while the control group (CG) received a text-only cessation information app. Both groups received brief advice from a healthcare professional. Main outcome measuresThe prespecified primary outcome was self-reported 7-day point-prevalence abstinence from combustible tobacco at 6 months post-randomisation; secondary outcomes included biochemical validation of abstinence in participants providing a saliva sample (59% of eligible participants). ResultsSelf-reported abstinence (primary outcome) was significantly higher in the IG compared with the CG (283 [39.3%] vs. 182 [24.4%], OR=2.01, 95% CI 1.60 to 2.50, p<0.0001). The NNT was 6.7 (5.1 to 9.8). The effect was consistent with biochemical validation (OR=1.76, 95% CI 1.27 to 2.44, p<0.0001) and across secondary outcomes and sensitivity analyses. The 6-month follow-up rates for the primary outcome did not differ between groups (IG: 601 [83.5%]; CG: 632 [84.7%]; p=0.52). Eighty-four serious adverse events were reported by 75 participants (IG: 31, 4.3%; CG: 44, 5.9%; p=0.53); none were treatment-related. ConclusionsThe Smoke Free app is effective for aiding smoking cessation in at least moderately dependent cigarette smokers compared with an informational app when provided as an adjunct to brief advice from a healthcare professional. Trial registrationThe trial was registered with the German Clinical Trials Register (DRKS00031140). FundingSmoke Free 23 GmbH (for-profit company).

ObjectivesTo evaluate the effectiveness and cultural feasibility of family-supervised disulfiram as a first-line treatment for alcohol use disorder (AUD) in Sri Lanka, and to compare its clinical outcomes with standard therapy delivered at a tertiary psychiatric unit. DesignSingle-blind Randomized Controlled Trial known as ETAT-RCT (Efficacy of Two Alcohol Treatments) was conducted under routine clinical setup with three parallel groups: family-supervised disulfiram, locally developed psychosocial intervention, and routine treatment. Allocation was independently concealed; assessors were blinded. Analyses followed an intention-to-treat approach using repeated-measures ANOVA (group x time). This paper reports the disulfiram (test) versus routine treatment (control) comparison; the psychosocial intervention will be reported separately. SettingUniversity Psychiatry Unit, National Hospital of Sri Lanka, Colombo (UPU, NHSLC). ParticipantsPatients aged [&ge;]14 years with AUD presenting to the unit were recruited consecutively without inducements. Planned allocation ratio was 1:1:1 with 31 participants per arm; key exclusions were lifetime psychotic disorder and current contraindication to disulfiram. RandomisationParticipants were randomised into each treatment arm using an independent concealed paper-based allocation system. Intervention(1) family-supervised disulfiram, with psychoeducation/support only - DT arm, (2) a locally developed denormalization focused psychosocial programme - PT arm, and (3) standard therapy (motivational/cognitive/behavioural input; naltrexone permitted; no disulfiram/denormalisation) - ST arm. Outcome measuresPrimary outcome was Alcohol Use Disorders Identification Test (AUDIT) score at 12 months. Key secondary outcomes were past 30 day alcohol use via Timeline Follow-Back (TLFB); alcohol biomarkers [ALT (alanine aminotransferase), {gamma}-GT (gamma-glutamyl transferase), MCV (mean corpuscular volume)]; locally developed measures of addiction-relevant cognitive, affective, behavioural factors [AARSU (Attitude Assessment Related to Substance Use), BARSU (Behaviour Assessment Related to Substance Use)]; and Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Outcomes were assessed at baseline, 6, and 12 months. ResultsParticipants in DT (n=33) and ST (n=38) were comparable at baseline. Both groups showed clinically and statistically significant improvement in AUDIT scores over 12 months (DT: F=39.90, p<0.001; ST: F=49.90, p<0.001), with no groupxtime interaction (F<0.001, p=0.98). Biomarkers and AARSU, and BARSU and Q-LES-Q-SF to a lesser degree, mirrored the AUDIT pattern. TLFB did not change significantly over time in either arm (p>0.05). In moderator analyses, improvement in AUDIT was not moderated by baseline motivation (F=0.20, p=0.89) but was moderated by baseline AUD severity (F=7.70, p=0.007). No serious adverse events were attributed to disulfiram. Adherence to supervised dosing was generally high during periods of supervision but intermittent overall. ConclusionsIn this pilot RCT, family-supervised disulfiram achieved 12-month outcomes comparable to standard therapy in a tertiary Sri Lankan setting. Improvements were independent of baseline motivation and varied by baseline AUD severity. These findings may support family-supervised disulfiram as a culturally feasible first-line option in Sri Lanka; larger, adequately powered multicentre trials are warranted to confirm effectiveness and scalability. Trial registrationSLCTR/2014/021 Strengths and limitations of this studyO_LIThis pragmatic randomised controlled trial demonstrates an improved real world applicability and validity as it was conducted in an unmodified public-sector psychiatric setting. C_LIO_LIStrong generalisability of the study with similar health systems due to broad eligibility criteria of patients warranted the inclusion of regular and general patient cohort with alcohol use disorders, strengthening generalisability within similar health systems. C_LIO_LIInterventions were carried out without additional staff or patient monitoring reflecting routine clinical practice. C_LIO_LIComprehensive assessment beyond abstinence alone with multidimensional outcomes such as alcohol related harm, biomarkers, cognitive behavioural change and quality of life. C_LIO_LIMinor potential in performance bias due to the nature of intervention where blinding study subjects and clinicians is not feasible. C_LIO_LISampling bias towards males and variability within the ST arm can affect the generalisability. C_LI

IntroductionMonitoring trends in transitions in the use of electronic nicotine delivery systems (ENDS) and cigarettes among youth is important for understanding the potential public health impacts of these products. MethodsUsing a weighted Markov multistate transition model accounting for complex survey design, we estimated transition rates and one-year transition probabilities between never, non-current, ENDS-only, and cigarette use (with or without dual use of ENDS) among 26,744 youth aged 12-17 years who participated in at least two consecutive waves from Waves 2-7.5 (approximately 2015-2023) of the nationally representative Population Assessment of Tobacco and Health (PATH) Study. We also estimated transitions stratified by ages 12-14 and 15-17 years. ResultsThe one-year probability of ENDS-only initiation from never use among youth peaked in 2017-19 (Waves 4-5) at 4.0% (95%CI: 3.6-4.3%) and was higher for 15-17-year-olds at 5.8% (95%CI: 5.2-6.4%) than 12-14-year-olds at 2.2% (95%CI: 1.8-2.6%). In the following years, ENDS-only initiation rates declined and plateaued, with 2.6% (95%CI: 2.3-3.0%) initiation in 2022-23. Cigarette initiation from never use decreased over 2015- 23 from 0.8% (95%CI: 0.6-1.0%) in 2015-16 to 0.1% (95%CI: 0.0-0.2%) in 2022-23. There was an increase in the fraction of youth who transitioned from non-current product use to ENDS-only use from 13.7% (95%CI: 7.5-20.0%) in 2015-16 to 35.1% (95%CI: 25.4-44.8%) in 2022-23, paired with a decrease in non-current use to cigarette use from 20.9% (95%CI: 11.8-30.0%) to 6.3% (95%CI: 1.7-10.8%). Transitions from ENDS-only or cigarette use to non-current use remained relatively constant over time at around 25% and 15% per year, respectively. ConclusionENDS-only use initiation has changed over time, peaking around 2019 and subsequently decreasing and plateauing, but cessation rates for both ENDS and cigarettes have remained relatively stable. Thus, interruption of tobacco product initiation may be the most effective approach to reducing tobacco product use among youth. What this paper addsWhat is already known on this topic: O_LITransitions in cigarette and ENDS use have changed over time, with youth more likely to adopt ENDS and less likely to adopt cigarettes than older age groups. C_LI What this study adds O_LIWe found that ENDS initiation among youth peaked around 2019 and was higher for those 15-17 years than 12-14 years. There were few significant differences between the two age groups for other transitions. C_LIO_LICigarette initiation among youth declined over this period. Cessation rates for both ENDS and cigarettes have remained relatively stable. C_LI How this study might affect research, practice or policy O_LITobacco control efforts should prioritize preventing all tobacco and nicotine product initiation among youth. C_LI

Objectives: Quantify hazardous alcohol consumption prevalence among individuals at risk of acquiring HIV infection and its association with high-risk sexual behaviors and incident HIV in 11 Eastern and Southern African countries. Design: Secondary analysis of 16 nationally-representative household surveys (2015-2023). Methods: The study included sexually active individuals aged [&ge;]15 years. Alcohol use patterns were classified using the AUDIT-C (non-drinkers/low-risk drinkers/hazardous non-binge drinkers/hazardous binge drinkers). Outcomes included high-risk sexual behaviors, recent HIV infection, and undiagnosed HIV infection. Survey-weighted alcohol use prevalence and logistic regression were estimated by gender, adjusting for sociodemographic covariates. Model outputs were used to estimate change in incident infections when removing excess risks associated with alcohol use patterns. Results: Analyses included 251,931 participants. Across countries, 5.8%-21.1% reported hazardous binge drinking, and 3.7%-15.7% reported hazardous non-binge drinking, with large gender differences. Sexual risk behaviors increased with drinking severity among men and women. Compared with non-drinkers, alcohol use was associated with higher odds of undiagnosed HIV infection; adjusted odds ratios ranged from 1.32 (1.16-1.50) for low-risk drinkers to 1.52 (1.34-1.72) for hazardous binge drinkers among men, and 1.28 (1.13-1.46) to 1.55 (1.31-1.82) among women. Simulated removal of alcohol-associated excess risk reduced undiagnosed HIV by 15.1% (10.9%-19.4%) among men and 5.8% (4.0%-7.9%) among women. Estimates for recent HIV infection followed a similar pattern but with larger uncertainty. Conclusions: Hazardous alcohol use was associated with sexual risk and HIV infection in Eastern and Southern Africa. Reaching individuals who use alcohol with effective HIV prevention may reduce HIV acquisition risk across the region.

Abstract Importance: The overall prevalence of youth nicotine and tobacco product use has declined over recent years, but the product landscape continues to evolve rapidly, particularly with new disposable e-cigarettes and oral nicotine pouches. Objective: To examine changes between 2024 and 2025 in the prevalence of nicotine and tobacco product use among US middle and high school students and describe shifts in product characteristics among current e-cigarette and nicotine pouch users. Design, Setting, and Participants: Repeated cross-sectional study using nationally representative data from the 2024 and 2025 National Youth Tobacco Survey (NYTS), a school-based survey of US students in grades 6-12 (approximately ages 11-18). The analytic sample included 29,678 students in 2024 and 23,557 students in 2025. Exposures: Survey year (2025 vs 2024). Main Outcomes and Measures: Past 30-day use of nicotine/tobacco products, including e-cigarettes, nicotine pouches, cigarettes, and other combustible and non-combustible products. Among current e-cigarette and nicotine pouch users, frequency of use, device type, brands, and flavors were assessed. Results: In 2025, 7.2% (95% CI, 6.4-8.2%) of US middle and high school students reported past 30-day use of any nicotine/tobacco product, compared with 8.1% (7.4-8.9%) in 2024. E-cigarettes remained the most commonly used product (5.2%, 4.5-5.9%); 1.7% (1.4-2.1%) used nicotine pouches, 1.7% (1.4-1.9%) smoked cigarettes, and 2.7% (2.4-3.1%) smoked any combustible tobacco product. Among current e-cigarette users, 40.7% (36.7-44.9%) reported frequent use and 27.0% (24.0-30.2%) reported daily use in 2025. Disposable e-cigarette use increased from 55.8% (52.6-59.0%) in 2024 to 66.7% (62.5-70.7%) in 2025, while pod/cartridge device use declined. Flavored product use was reported by 90.0% of e-cigarette users and 88.0% of nicotine pouch users. The most commonly reported brands were Geek Bar among e-cigarette users (61.1%) and ZYN among nicotine pouch users (69.4%). Conclusions and Relevance: Overall youth nicotine and tobacco use remains relatively low, but the product landscape is evolving rapidly, with increasing disposable device use and shifting brand preferences. These findings highlight the importance of ongoing, product-specific surveillance to inform public health strategies and regulatory policies.

Introduction: The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) is a widely utilized screening tool in large-scale electronic health record (EHR) biobanks. However, its categorical, range-based survey responses present a significant challenge for epidemiological research, especially where continuous quantitative variables may be preferred. Standard workarounds, such as assigning categorical midpoints or utilizing aggregate ordinal scores for regression mapping often introduce false mathematical precision or obscure critical behavioral nuances between drinking frequency and quantity. This report presents a novel framework for presenting and bounding categorical alcohol survey data. Materials and Methods: I developed two complementary descriptive techniques: (1) a two-dimensional cross-tabulation matrix that preserves the interaction between drinking frequency and typical quantity, and (2) a systematic bounding algorithm that applies time-interval correction factors to calculate strict lower and upper estimates of average daily alcohol consumption. To demonstrate the real-world utility of this framework, I applied these methods to three analytical descriptive scenarios within a European ancestry (EUR) cohort of the All of Us Research Program: Generalized Anxiety Disorder (GAD) prevalence (n=104,893), minor allele frequency (MAF) for the rs1229984 genetic variant (n=104,890), and self-reported active duty military service history (n=104,893). Results: Application of the cross-tabulation matrix revealed patterns across all three descriptive scenarios. For example, participants reporting the highest frequency ("4 or more times a week") combined with the highest quantity ("10 or More" drinks) demonstrated a GAD prevalence of 13.5%, compared to 5.8% among those reporting the same frequency but a low quantity ("1 or 2" drinks). A general trend of increased anxiety in higher quantity drinkers contrasts with a general trend of decreased anxiety in higher frequency drinkers. Bounding estimates for average daily consumption ranged from 0.299 to 0.730 drinks for individuals with GAD, and 0.303 to 0.787 for those without. Those who reported having been active duty in the US Armed Forces demonstrated a general trend toward more frequent drinking and higher average daily consumption estimates (0.339 to 0.875) than those who had not (0.297 to 0.770). The minor allele of the genetic variant rs1229984 exhibited a clear effect reducing both frequency and quantity, resulting in lower average daily consumption estimates. Conclusions: This bounding and mapping framework provides researchers with an additional method to traditional midpoint and aggregate scoring methods. By explicitly defining the uncertainty inherent in categorical survey instruments and visualizing cohort distributions across intersecting behavioral axes, this methodology improves the resolution, reproducibility, and interpretability of lifestyle exposure data.

Abstract Aims To examine which demographic groups nicotine pouch advertisers chose to target on social media, and which groups Meta's algorithms actually delivered the adverts to. Design Cross-sectional analysis of advert-level data from the Meta Ad Library. Setting Meta social media platforms (including Facebook and Instagram) in the UK. Cases A random sample of 741 nicotine pouch adverts shown in the 12 months up to December 2025, and a comparison sample of 1,125 general adverts. Analyses of reach were restricted to adverts eligible for all genders and adult ages (444 pouch adverts; 674 general). Measurements Outcomes were advertiser-set gender and age-group targeting criteria (i.e., groups eligible to be shown each advert) and estimated advert reach to each group (i.e., number of people who saw each advert). Male-to-female reach ratios within age groups, and reach ratios comparing age groups, were calculated per advert and summarised using geometric means. To assess whether patterns were pouch-specific, comparisons with general adverts were made using ratios of reach ratios (RRR). Findings Advertisers of nicotine pouches targeted a broad sample; most adverts (79.1%; 586/741) were eligible to be shown to all genders, the remainder were restricted to men only. All were restricted to adults (minimum age 18 years) and most (95.6%; 708/741) had no upper age limit. Despite this, of pouch adverts eligible to be shown to all adults, adverts were more likely to reach men, particularly among younger men. Among 18-24-year-olds, pouch adverts reached around ten times as many men as women (RR 10.0, 95% CI 8.7-11.5), compared with a slight skew towards women for general adverts (RR 0.81, 95% CI 0.71-0.94), corresponding to an RRR of 12.3 (95% CI 10.0-15.1). Pouch adverts also showed a skew in reach towards younger age groups. Relative to those aged 35-44 years, reach was higher among 18-24-year-olds for nicotine pouch adverts (RR 1.33, 95% CI 1.17-1.51) but much lower for general adverts (RR 0.19, 95% CI 0.17-0.21), corresponding to an RRR of 7.0 (95% CI 6.0-8.2). Conclusions Nicotine pouch adverts on social media are often eligible to be shown broadly to all demographic groups but are disproportionately delivered to young men.

ABSTRACT Background and aims: Mental and behavioral disorders due to use of tobacco (MBDT) present a critical challenge to global health, yet modifiable lifestyle factors for reducing its risk remain poorly understood. Given that dietary fibre can affect mental health through gut-brain communication, we sought to explore how fibre intake relates to MBDT risks in smokers. Methods: We specifically evaluated the link between dietary fibre intake and MBDT within a smoking population. Utilizing the UK Biobank (UKB) database, we performed cross-sectional (N=19,943) and prospective cohort (N=19,885) evaluations applying logistic and Cox proportional hazards models, respectively. To determine potential causality, two-sample Mendelian randomization (MR) was applied, relying on GWAS summary data derived from the IEU Open GWAS Project and FinnGen repositories. Results: Cross-sectional findings indicated that individuals in the top quartile (Q4) of fibre intake exhibited decreased MBDT risks relative to the bottom quartile (Q1) (OR: 0.32, 95% CI: 0.13-0.79). Over a median observation time of 12.84 years, the prospective evaluation demonstrated a notable inverse correlation (Q4 HR: 0.46, 95% CI: 0.40-0.54). Non-linear modeling via restricted cubic splines uncovered an L-shaped dose-response curve. Furthermore, MR results confirmed a genetically predicted protective causality (IVW OR: 0.68, 95% CI: 0.49-0.95), which remained consistent across sensitivity validations. Conclusions: Among smokers, higher dietary fibre intake is robustly associated with a reduced risk of mental and behavioral disorders due to the use of tobacco, offering a modifiable dietary target for public health interventions.

Background and AimsOn April 1st, 2024, Germany implemented the Act on the Handling of Cannabis for Non-Medical Use (KCanG), allowing adults to cultivate and possess recreational cannabis. We assessed whether this policy shift was associated with a change in the prevalence of cannabis use in the general population and in daily or almost daily cannabis use. DesignA series of 21 repeated cross-sectional surveys conducted between April/May 2022 and October/November 2025 (covering the period approximately two years before and one and a half years after the KCanG). SettingPopulation of Germany. ParticipantsA total of 32,991 people aged 14-64 years, including 2,092 (6.3%) people who used cannabis in the past 12 months. MeasurementsPast 12-month cannabis use (at least once). In past 12-month users: daily or almost daily use. To test a potential change in prevalence following the KCanG, we used piecewise binomial logistic regression models using the exact date of each wave as the predictor variable, allowing for a change in the slope at the first full wave after implementation of the KCanG in April 2024, with a random effect for wave. We conducted this analysis for the total sample as well as stratified by gender (male vs. female), age (14-24 vs. 25-64 years), and for daily or almost daily cannabis use in the subgroup of people who used cannabis in the past 12 months. Sensitivity analyses used alternate intervention dates (in-time placebo tests). FindingsThe prevalence of cannabis use and the share of (almost) daily users among 12-month users remained largely stable before and after the law reform. None of the slope coefficients before the introduction of the KCanG were statistically significant (all p [&ge;] .08), and none of the coefficients for the change in the slope were statistically significant (all p [&ge;] .31). Results of sensitivity analyses confirmed the stable trends for both outcomes. ConclusionsThe legislation of cannabis introduced in Germany in April 2024 was not associated with a change in trends of 12-month cannabis use prevalence early (1.5 years) after implementation, and also not with a change in the proportion of heavy users among past-12-month users. We recommend continued close monitoring of trends using multiple data sources and over a longer post-implementation period, as the effects of the legislation may not have fully unfolded yet.

Importance: Understanding patterns of substance use and environmental exposures to tobacco, cannabis, and electronic nicotine delivery systems (ENDS) among youth is critical for developing targeted prevention strategies, particularly as co-use of tobacco, ENDS, and cannabis becomes more prevalent. Objective: To identify latent classes of tobacco, ENDS, and cannabis use, and environmental exposures to these products among adolescents and emerging adults. Design, Setting, and Participants: Data from the Environmental influences on Child Health Outcomes (ECHO) consortium (3rd data release, 2018 to 2022) were analyzed from March 2025 to January 2026. The sample (N=2,786) included early adolescents (ages 11 to 13; n=226, 7.9%), middle adolescents (ages 14 to 17; n=1,248, 43.4%), and late adolescents/emerging adults (ages 18 to 24; n=1,402, 48.7%) from 19 ECHO cohorts. Main Outcomes and Measures: The Youth Risk Behavior Survey, Substance Use module measured experimental and current use of cannabis, ENDS, and tobacco products, as well as daily environmental exposure to tobacco smoke, nicotine aerosols, and cannabis smoke within home and social contexts. A multiple group latent class analysis was used to identify distinct latent classes of substance use and environmental exposure to tobacco smoke, nicotine aerosols, and cannabis smoke and compared class prevalences across early, middle, and late adolescence. Results: Four latent classes were identified, including: No Use/No Exposure (53%), No Use, Polyexposure (10%), Experimental Use/Low Exposure (22%), and Polysubstance Use/High Polyexposure (14%). Cannabis was the most used substance (34% experimental or current use) and the most common source of environmental exposure (20%), followed by ENDS use (26% experimental or current use; 19% environmental exposure) and combustible tobacco (15% use; 19% environmental exposure). The No Use/No Exposure and No Use/Polyexposure classes were primarily made up of early and middle-aged adolescents, whereas the Experimental Use/Low Exposure and Polysubstance Use/High Polyexposure classes primarily consisted of late adolescents and emerging adults. Conclusions: Our study revealed distinct, developmentally patterned groupings of substance use and environmental exposure among US adolescents and emerging adults, highlighting the need for developmentally tailored interventions, messaging, and policies that address both active use and environmental exposure across adolescence.

Objectives: This meta-review compares methodological and reporting approaches between systematic reviews examining alcohol dose and cardiovascular disease (CVD) and assesses whether alcohol industry involvement is associated with divergent conclusions. Methods: KSR Evidence was searched 6 May 2025 to update a cohort of 60 systematic reviews from previous review. Reviews were included if they examined any dose-response relationship between alcohol consumption and CVD. Two reviewers independently screened records and extracted data on review characteristics, and citations. Methodological quality was appraised using AMSTAR 2. For a matched sample of reviews with and without known alcohol industry funding, the overlap of included primary studies was compared using Corrected Covered Area (CCA) analysis. Results: Thirty additional systematic reviews met the inclusion criteria, yielding 90 systematic reviews (1996-2025). Most (60.0%, 54/90) concluded that alcohol had a cardioprotective effect, whereas 31.1% (28/90) concluded no evidence of protection, and 8.9% (8/90) were inconclusive. Twenty reviews (22.0%) had declared or inferred alcohol industry funding or author connection; all but one reported a protective effect at lower doses, the other was inconclusive. Industry-connected reviews were cited more often (mean 575.9 vs 193.0, p=0.0002) and more commonly examined overall CVD rather than specific conditions (such as hypertension or stroke). Study overlap was low (CCA 2.59%) and 99% of reviews were rated as critically low quality. Conclusions: The fragmented evidence base is of poor methodological quality with selective inclusion of studies. Alcohol industry connections are strongly associated, with conclusions favouring alcohol consumption, highlighting the need for independent high-quality systematic reviews.

Background The clinical safety profile of e-cigarette use for smoking reduction remains poorly characterized. This study compared the relative safety and tolerability of nicotine e-cigarette use with non-nicotine e-cigarettes or a non-aerosol cigarette substitute (CS) among adults interested in reducing their smoking. Methods We conducted a secondary analysis of adverse events (AEs) reported in a 6-month, double-blind RCT involving 520 participants assigned to either e-cigarettes with 0, 8, or 36 mg/mL nicotine or a CS. AEs were coded using CTCAE V4.0 and assessed for frequency, severity, seriousness and relatedness across groups. Cumulative incidence was calculated over 24 weeks. We estimated risk differences (RDs) and 95% confidence intervals (CIs) for frequently reported AEs (>=1% of participants overall) comparing e-cigarette vs. CS and nicotine versus non-nicotine e-cigarette groups. Fisher's exact test, with adjustment for multiple comparisons, was used to assess statistical significance. Results Most study-related AEs (those rated as possibly, probably, or definitely related by medical monitor) were mild in severity and none were classified as serious. At 24 weeks, cumulative incidence of first study-related AE was highest in the 36 mg/mL (37.0%) and 8 mg/mL (35.2%) e-cigarette groups, followed by 0 mg/mL (23.4%), and lowest in CS group (2.5%). E-cigarette users experienced significantly greater risks of cough (RD [95%CI]: 8.5% [5.6-11.3]), headache (RD [95%CI]: 5.4% [3.3-7.6]) and sore throat (RD [95%CI]: 5.4% [3.2-7.6]) as compared with the CS group. Cough was also more common in those randomized to nicotine versus non-nicotine e-cigarettes (RD [95%CI]: 8.1% [3.4-12.8]). Conclusion All study products were generally well-tolerated; however, AEs were more common in e-cigarette groups, especially with nicotine. Findings highlight the need to monitor common symptoms such as cough, headache, and sore throat in clinical and regulatory evaluations of e-cigarette safety.

IntroductionAlthough prior studies suggest e-cigarette use is associated with worse mental health, it remains unclear whether these associations persist independent of diagnosed depression and how tobacco use and depression jointly affect health-related quality of life. Although the long-term health risks of vaping are still unknown, self-reported health is a reliable measure of quality of life. This study provides the first health utility estimates of the independent and combined effects of cigarette use, e-cigarette use, and depression on health-related quality of life. MethodsWe analyzed 2022-2023 Behavioral Risk Factor Surveillance System data on health-related quality of life as measured by self-reported physically or mentally unhealthy days in the past 30 days. The average number of unhealthy days was estimated by age, gender, smoking status (current versus non-smoking), depression status (received a prior diagnosis), and current e-cigarette use status (every day or some day use). We converted the number of overall healthy days into EQ-5D utility scores by age-specific percentile matching of BRFSS and MEPS distributions, a method developed by Jia and Lubetkin. ResultsCigarette use, e-cigarette use, and depression were each associated with worse health-related quality of life. Mentally unhealthy days increased with the accumulation of these conditions. Associations with physically unhealthy days followed a similar pattern, particularly among younger adults, although the magnitude of association was smaller. E-cigarette use alone was associated with 2.0-4.2 (95% CI: 2.0-4.6) additional mentally unhealthy days per month across all age groups. Notably, e-cigarette use was independently associated with poorer mental health among adults aged 18-64 with or without diagnosed depression. After accounting for smoking and depression status, e-cigarette use was associated with disutility scores of 0.011 in men and 0.015 in women among young adults, with the largest losses observed when multiple conditions co-occurred. ConclusionE-cigarette use is associated with poorer health-related quality of life, particularly among younger adults, and these effects are amplified when combined with cigarette use and depression. Quantifying these joint impacts as health utility losses highlights the importance of addressing e-cigarette use within integrated tobacco control and mental health policies, especially for young populations.

Substance use disorders run in families, yet the mechanisms underlying intergenerational transmission remain unclear. We investigated indirect genetic effects, pathways through which parental genotypes influence offspring phenotypes via the family environment, for alcohol use disorder (AUD), nicotine dependence (ND), and related quantitative outcomes, and aimed to identify family environmental factors through which such effects may operate. Using transmitted and non-transmitted polygenic scores (PGS) constructed for problematic alcohol use, tobacco use disorder, and general addiction liability, we analyzed 5972 European-ancestry adult offspring with at least one genotyped parent from the population-based Lifelines cohort (Netherlands). Offspring outcomes included lifetime DSM-5 AUD diagnosis, AUD symptom count, maximum drinks in 24 hours, Fagerstrom Test for Nicotine Dependence score, and cigarettes per day. AUD findings were meta-analyzed with data from the Brisbane Longitudinal Twin Study (N = 1368; Australia). We also examined parent-of-origin effects and mediation by parental substance use and socioeconomic status using structural equation modeling. Transmitted PGS robustly predicted all AUD and ND outcomes ({beta} = 0.07-0.16; OR = 1.20 for AUD diagnosis). Non-transmitted PGS, indexing indirect genetic effects, were negligible for all clinical syndrome outcomes. The only significant indirect genetic effect was on cigarettes per day ({beta} = 0.03, p = 0.01), mediated by parental smoking behavior but not socioeconomic status. These findings indicate that intergenerational transmission of risk for AUD and ND is driven primarily by direct genetic effects, with modest indirect genetic effects on smoking quantity. Larger samples and cross-trait analyses are needed to further elucidate these mechanisms.

Background: Xylazine and medetomidine are veterinary sedatives increasingly detected as adulterants in the U.S. illicit drug supply. In response, several states have scheduled xylazine. Whether these policies are associated with subsequent changes in xylazine and medetomidine detections remains unclear. Methods: We conducted a state-level, semiannual, serial cross-sectional study using National Forensic Laboratory Information System (NFLIS) data from 1999 to 2025. The primary outcomes were xylazine and medetomidine reports per 100,000 NFLIS drug reports. We used staggered difference-in-differences event-study models to estimate changes in report rates after xylazine scheduling. Sensitivity analyses excluded Florida and expanded the treatment definition to include states that criminalized xylazine without formal scheduling. Falsification analyses examined steroid and antidepressant reports as negative-control outcomes. Results: NFLIS recorded 101,987 xylazine reports and 12,085 medetomidine reports. Xylazine scheduling was not associated with a significant change in xylazine report rates (ATT, 2,872.29 per 100,000; 95% CI, -2,024.63 to 7,769.21; p=.250). In contrast, xylazine scheduling was associated with a significant increase in medetomidine report rates (ATT, 1,536.51 per 100,000; 95% CI, 211.14 to 2,861.88; p=.023). Sensitivity analyses produced similar findings. Negative-control outcomes showed no significant changes. Conclusions: State xylazine scheduling was associated with increases in medetomidine reports but no significant change in xylazine reports. These findings suggest that scheduling may be followed by changes in adulterant composition rather than reductions in overall 2-adrenergic agonist involvement. Our study highlights the importance of monitoring the unintended effects of xylazine scheduling and supporting continued investment in public health surveillance, drug checking, and harm reduction services.

BackgroundThe initiation of tobacco and nicotine product use often occurs in adolescents. This necessitates monitoring of this behaviour in this population, particularly in countries such as the Democratic Republic of the Congo (DRC) where approximately 58% of the population is under 19 years of age. Our study assessed the prevalence of, and factors associated with use in the DRC. MethodsWe conducted a nationally representative, cross-sectional, household survey between March and May 2024 among adolescents aged 10 to 17 years. We estimated the prevalence of use of smoked and smokeless tobacco products, heated tobacco products, and nicotine products (i.e., electronic cigarettes and nicotine pouches). We used logistic regression to identify factors associated with current use of any tobacco product, smoked tobacco, and smokeless tobacco using adjusted odd ratios. All analyses included 95% confidence intervals (CI). ResultsOf the 4,675 adolescents who completed the survey, the prevalence of current use of any tobacco or nicotine product was 11.87% (95% CI: 6.93-19.58). This was 7.98% (95% CI: 4.23-14.55) for smoked tobacco products, 5.86% (95% CI: 3.42-9.87) for smokeless tobacco products, 0.11% (95% CI: 0.11-0.11) for heated tobacco products and 0.60% (95% CI: 0.10-3.40) for nicotine products. Boys were more likely to use tobacco than girls. Being enrolled in school and having both parents alive were protective from tobacco use. Having a male household head, a household head education level of at least secondary school, and exposure to tobacco smoking in public places increased the odds of being a tobacco user. ConclusionsThe DRC should strengthen policies that make tobacco and nicotine products less accessible or appealing to adolescents. This includes raising excise taxes; banning the sale of single cigarette sticks, small packets and flavoured products; and comprehensive smoke-free laws. Policies should account for factors that make adolescents more vulnerable product use. Key messagesO_ST_ABSWhat is already known on the topicC_ST_ABSO_LIThe last survey on tobacco use among adolescents in the DRC was a school-based survey among 13-15-year-olds conducted in 2008, and only covered Kinshasa and Lubumbashi. C_LI What this study addsO_LIThis survey provided national-level estimates that cover adolescents aged 10-17years, includes out-of-school adolescents, and covers both tobacco and nicotine products. C_LIO_LIIt also identifies individual-, household-, and environmental-level factors that are associated with tobacco and nicotine product use among adolescents in the DRC. C_LI How this study might affect research, practice or policyO_LIBy providing current and more comprehensive data, our study enhances policymakers ability to design evidence-based tobacco control interventions that are aimed at preventing the initiation and use of tobacco and nicotine products among adolescents in the DRC and other similar settings. C_LI

Tobacco control treaties were written for billboards and television, not for the people now selling lifestyles to young Africans. As mobile internet saturates East African cities, social media influencers have become an unmeasured channel, especially when it comes to tobacco promotion. We assessed the prevalence of tobacco use, its association with influencer exposure, and how urban youth interpret that exposure in two capitals with different tobacco laws. We conducted a comparative mixed-methods study among youth aged 18-29 years in Kampala, Uganda, and Nairobi, Kenya (January-August 2025), combining (i) a cross-sectional survey using systematic sampling at youth-dense venues (n=772), (ii) four online focus group discussions (FGDs; n=40), and (iii) content analysis of 30 tobacco-related posts from high-reach influencers (greater than 50,000 followers). We used chi-square tests and multivariable logistic regression, thematic analysis (Braun and Clarke), and descriptive engagement metrics. Ever tobacco use among urban youth in East Africa was 29.3% (226/772), similar in Kampala (30.7%) and Nairobi (28.0%; p=0.409). After adjustment, exposure to influencers promoting tobacco independently predicted ever use (adjusted odds ratio [aOR] 1.90, 95% confidence interval [CI] 1.29-2.82; p=0.001), alongside male sex (aOR 2.35) and age 26-29 years (aOR 1.99). Tertiary education (aOR 0.45) and never seeing tobacco content (aOR 0.26) were protective. Posts framed tobacco as aspirational lifestyle; 77% of sampled comments were positive and 47.5% expressed interest in trying the product. Influencer exposure behaved as a modifiable risk factor of a magnitude comparable to established demographic drivers. Tobacco control in the region must move from print-era advertising bans to platform governance, mandatory disclosure of paid promotion, and youth-led counter-marketing.