Addiction

Background and AimsDue to the COVID-19 pandemic, the survey mode of the Smoking and Alcohol Toolkit Study, a long-running repeat cross-sectional survey, had to change from face-to-face to telephone interviews. This study aimed to assess similarities and differences in sociodemographic, smoking, alternative nicotine and alcohol use estimates between the two survey modes, to understand the potential impacts of this change in methodology on prevalence estimates and trends over time. DesignAfter COVID-19 restrictions were lifted, we conducted parallel telephone and face-to-face household surveys in March 2022 and in January to March 2024, using a hybrid of random and quota sampling. Data from both years were aggregated. Setting and ParticipantsPeople aged 16+ years living in private households in Great Britain. MeasurementsSociodemographic characteristics, nicotine and alcohol use related estimates and their 95% CIs -- unweighted and weighted -- collected via telephone versus face-to-face in a household. FindingsIn the unweighted analyses, the telephone sample included slightly younger and less socioeconomically advantaged groups than the face-to-face sample. After the samples were weighted, estimates of sociodemographic characteristics and nicotine and alcohol use were generally consistent across methodologies, including daily cigarette smoking (face-to-face: 11.1% [10.1-12.1] vs. telephone: 10.6% [9.5-11.7]), non-daily cigarette smoking (face-to-face: 2.7% [2.2-3.3] vs. telephone: 3.4% [2.8-4.1]), and e-cigarette use among people who smoke (face-to-face: 27.0% [23.5-30.5] vs. telephone: 29.3% [25.4-33.3]). However -- compared with telephone participants -- a lower proportion of face-to-face participants reported currently using e-cigarettes (face-to-face: 6.4% [5.6-7.1] vs. telephone: 10.4% [9.3-11.5]), and a higher proportion reported never drinking alcohol (face-to-face: 31.1% [29.7-32.5] vs. telephone: 25.0% [23.5-26.5]) and never having 6 or more standard drinks on one occasion (face-to-face: 46.6% [44.7-48.5] vs. telephone: 40.2% [38.4-42.1]). More participants provided "dont know" or "refused" responses in the telephone compared with the face-to-face interview, including in response to questions about tobacco use, e-cigarette device type, and the number of standard drinks on a typical day. ConclusionsFace-to-face and telephone surveys generally yield similar estimates of nicotine and alcohol use. However, there may be some underreporting of vaping and drinking in a face-to-face survey conducted in the home compared with telephone.

BackgroundMethamphetamine (MA) use is disproportionately higher among people living with HIV (PWH) and contributes to adverse clinical outcomes. Accurate measurement of MA use is essential for research and care but remains inconsistent. MethodsA systematic review of PubMed, Embase, and CINAHL identified 22 peer-reviewed studies (2019-2024) assessing MA use in HIV-positive adults. Data were extracted on measurement methods, demographic composition, and HIV outcomes. ResultsStudies employed self-report, urine or hair toxicology, and medical record review. Reporting varied widely in timeframe, frequency, and specificity, with limited detail on route of administration. Most studies were U.S.-based, disproportionately male, and rarely included women or gender-diverse participants. Inconsistent definitions and reliance on broad stimulant categories limited comparability. ConclusionsCurrent methods for assessing MA use in PWH lack standardization. Greater consistency, inclusion of biological validation, and expanded demographic representation are needed to strengthen research and clinical interventions.

IntroductionDespite freely available HIV pre-exposure prophylaxis (PrEP), HIV incidence among young men in South Africa is high. There is conflicting evidence around the association between alcohol use behaviors and PrEP utilization. We explore the impact of alcohol use on PrEP initiation and continuation among South African men. MethodsWe performed a secondary analysis of data from a trial that included men aged 16-29 randomly selected from a demographic surveillance site in KwaZulu-Natal. All participants were referred to HIV and sexual health services, where those who were HIV negative and sexually active were offered oral PrEP. Alcohol consumption was assessed at monthly visits and categorized as: non-drinking (0), low/moderate risk drinking (1-5), and high/very high-risk drinking (6-12) based on AUDIT-C criteria. Primary outcomes were PrEP initiation and PrEP continuation defined as refilling prescriptions for >3 months. We fitted logistic regression models, adjusted for potential clinical and demographic confounders, to estimate relationships between PrEP initiation/continuation and reported alcohol use. ResultsOf the 325 men in the analytic cohort, the average age was 22.9 years (SD 3.6) and 131 (40%) had high/very high-risk alcohol consumption (AUDIT-C score [≥]6). Men with the highest risk alcohol use also reported more frequent condomless sex (89%, vs 68% in no alcohol group). We found the greatest uptake of PrEP among the high/very high-risk alcohol group (46/131, 35%), followed by the low/moderate-risk group (17/53, 32%) and the no alcohol group (25/141, 18%). Those with high-risk alcohol use remained more likely to initiate PrEP compared to the no alcohol group in multivariable models adjusted for confounders (aOR 2.44 95% CI 1.29-4.60; p-value 0.006). Overall, only 30% (26/88) of men remained on PrEP at 3 months. Men with high/very high-risk drinking had similar PrEP continuation at 3 months compared to men who reported no alcohol use (aOR 1.02 95% CI: 0.28-3.86, p=0.98). ConclusionsHigh-risk alcohol use is common among men in rural South Africa and associated with increased PrEP initiation. However, PrEP continuation was low overall, and similar across all levels of alcohol use. Hazardous alcohol use should not discourage PrEP implementation efforts to engage and retain young men.

AimsTo update a previous typology of British alcohol drinking occasions using a more recent and expanded dataset and revised modelling procedure. To estimate the average consumption level, prevalence of heavy drinking, and distribution of total alcohol consumption and heavy drinking within and across occasion types. DesignCross-sectional latent class analysis of event-level diary data. SettingGreat Britain, 2019. Cases43,089 drinking occasions reported by 17,821 adult drinkers. MeasurementsThe latent class indicators are characteristics of off-trade only (e.g. home), on-trade only (e.g. bar) and mixed trade (e.g. home and bar) drinking occasions. These describe companions, venue(s) and location, purpose, motivation, accompanying activities, timings, weekday, consumption volume in units (1 UK unit = 8g ethanol) and predominant beverage consumed. FindingsThree latent class models identified four off-trade only occasion types (i.e. latent classes), eight on-trade only occasion types and three mixed-trade occasion types. Mean consumption per occasion varied between 4.4 units in Family meals to 17.7 units in Big nights out with pre-loading. Mean consumption exceeded ten units in all mixed-trade occasion types and in Off-trade get togethers, Big nights out and Male friends at the pub. Three off-trade occasion types accounted for 50.8% of all alcohol consumed and 51.8% of heavy drinking occasions: Quiet drink at home alone, Evening at home with partner and Off-trade get togethers. For thirteen out of fifteen occasion types, more than 25% of occasions involved heavy drinking. Conversely, 41.7% of Big nights out and 16.4% of Big nights out with preloading were not heavy drinking occasions. ConclusionsAlcohol consumption varies substantially across and within fifteen types of drinking occasion in Great Britain. Heavy drinking is common in most occasion types. However, moderate drinking is also common in types often characterised as heavy drinking practices. Mixed-trade drinking occasions are particularly likely to involve heavy drinking.

BackgroundThe impact of the COVID-19 crisis on potentially harmful alcohol consumption is unclear. AimsTo test whether the prevalence of problem drinking has changed from before to during the COVID-19 crisis in the US and UK. Design/SettingWe examined nationally representative longitudinal data on how problem drinking has changed from pre-pandemic levels among adults in the US (N=7,327; Understanding America Study) and UK (N=12,594; UK Household Longitudinal Study). MethodsIn the US, we examined rates of consuming alcohol [&ge;] 4 times in the past week at baseline (March, 2020) and across four waves of follow-up (April-May, 2020). In the UK we assessed the prevalence of consuming alcohol [&ge;] 4 times per week and weekly heavy episodic drinking using the AUDIT-C at baseline (2017-2019) and during the COVID-19 lockdown (April, 2020). We also tested whether there were specific groups at greater risk of increased problem drinking during the pandemic. ResultsAmong US adults, there was a statistically significant increase in the percentage of participants reporting drinking alcohol [&ge;] 4 times a week which rose significantly from 11.7% to 17.9% (53% increase, p < .001) as the COVID-19 crisis developed in the US. Among UK adults, the percentage of participants reporting drinking [&ge;] 4 times a week increased significantly from 14.2% to 23% (62% increase, p < .001) and heavy episodic drinking at least weekly increased significantly from 9.7% to 16.6% (71% increase, p < .001) when compared to pre-COVID-19 lockdown levels. Trends were similar across population demographics, although those aged under 50 years and higher income groups displayed the largest increases. ConclusionsThe COVID-19 crisis has been associated with substantial increases in problematic drinking in both US and UK adults.

BackgroundAlcohol-free and low-alcohol (no/lo) drinks ([&le;]1.2% ABV) are increasingly popular in high-income countries. Their potential to reduce alcohol-related harm depends on who buys them, in what quantity, and their incorporation into overall drinking patterns. We aimed to (i) compare characteristics of purchases containing only no/lo drinks, only alcoholic drinks, or both, over time between 2018 and 2023; (ii) identify subgroups with distinct purchasing patterns in 2023; and (iii) describe purchasing and soiodemographic differences between these subgroups. DesignLatent profile analysis of cross-sectional household purchasing data. SettingGreat Britain, 2018 and 2023. ParticipantsNationally representative samples of 30,401 (2018) and 28,254 (2023) households. 4,975 households who purchased no/lo drinks in 2023 were included in the latent profile analysis. MeasurementsData included off-trade (i.e. shop) purchases categorised into: no/lo-only; alcohol-only; or no/lo alongside alcohol. Household characteristics were frequency of each purchase type; standard servings of no/lo drinks per adult; alcohol risk levels based on weekly units of alcohol purchased per adult in household (non-drinker: 0 units; low-risk:[&le;] 14 units; increasing risk: >14[&le;] 35 units; high-risk: >35 units [1 unit = 8g alcohol]); household age; social class; region; and ethnicity. FindingsFrom 2018 to 2023, the proportion of purchases that were alcohol-only fell from 97% (95% CI: 97%-97%) to 95% (CI: 95%-95%) while no/lo-only purchases rose from 1.4% (CI: 1.3%-1.4%) to 2.7% (CI: 2.7%-2.8%) and no/lo alongside alcohol purchases rose from 1.2% (CI: 1.2%-1.2%) to 1.9% (1.9%-2.0%). In 2023, no/lo-only purchases contained fewer servings (median = 6.9) than no/lo alongside alcohol purchases (median = 6.5 plus 24.5 alcohol units) and alcohol-only purchases (median = 24.6 units). No/lo-only purchases occurred earlier in the week, no/lo alongside alcohol purchases peaked on Fridays and Saturdays. Latent profile analysis identified three classes: (i) no/lo triers (53%) averaged 2.1 no/lo servings per adult annually with 95% purchasing no or low-risk levels of alcohol. (ii) Occasional purchasers (34%) averaged 7.5 servings with 20% purchasing alcohol at increasing or high-risk levels. (iii) Dual purchasers (13%) averaged 37.8 servings with 39% purchasing alcohol at increasing or high-risk levels. Dual purchasers and occasional purchasers were older than no/lo triers (60% [p<0.001], 54% [p=0.010], and 49% 55 years respectively). Dual and occasional purchasers were more often white than no/lo triers (97% [p = 0.014], 97% [p=0.0074], 94% respectively). ConclusionsIn Great Britain, most households purchasing no/lo drinks do so infrequently and purchase alcohol at low-risk levels; however, a smaller group of older, higher-risk households purchase no/lo drinks more frequently.

ObjectiveMinimum unit pricing (MUP) aims to reduce use of cheap, high strength alcoholic beverages that drive harm, yet concerns remain about inequitable effects for structurally vulnerable groups. As part of the Costs, Harms, Expenditures and Alcohol Prices (CHEAP) study, we linked individual-level, product-specific alcohol consumption data from a customized survey with provincial retail price data to estimate prices per standard drink (PPSD) and examine their association with alcohol-related outcomes across sociodemographic groups. MethodA cross-sectional survey of past-week drinkers in British Columbia, Canada, was linked to provincial product-level alcohol sales data. The population weighted sample included 1,217 adults aged [&ge;] 19 years (716 men; mean age 49.34, SD 16.98). Participants reported product-specific consumption, which was matched to retail prices to calculate individual-level PPSD. Survey weighted quasibinomial models then examined associations between PPSD and three outcomes: (1) causing harm to self or others in the past year, (2) scoring [&ge;] 8 on the Alcohol Use Disorder Identification Test, and (3) consuming [&ge;] 15 standard drinks per week. Analyses were stratified by income, education, subjective social status, and race/ethnicity. ResultsLower price per standard drink was associated with higher odds of harm (OR 3.05, 95% CI 1.25-7.40) and scoring [&ge;] 8 on the AUDIT (OR 2.34, 95% CI 1.37-3.99). Associations were stronger among structurally disadvantaged groups, including low-income respondents and Indigenous participants. ConclusionsLower alcohol affordability is linked to risky alcohol use, with the strongest effects among structurally disadvantaged groups. MUP would reduce this risk and promote health equity.

Background and AimsHigh alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts. Approach and ResultsInformation was obtained from the UK Biobank on approximately 500,000 participants aged 40-70 years at baseline assessment in 2006-2010. Habitual alcohol intake, lifestyle and physiological data, laboratory test results, and hospital diagnoses and death certificate data (to June 2020) for 5136 men (2.20% of male participants) and 1504 women (0.60%) who reported taking [&ge;]80 g/day or [&ge;]50g/day, respectively, were used in survival analysis. Compared to all other participants, their mortality HRs were 9.40 (95% CI 7.00-12.64) for any liver disease (ICD-10 K70-K76), 2.02 (1.89-2.17) for all causes, 1.89 (1.69-2.12) for any cancer (C00-C99), and 1.87 (1.61-2.17) for any circulatory disease (I00-I99). Liver disease diagnosis or abnormal liver function tests predicted not only deaths attributed to liver disease but also those from cancers or circulatory diseases. Mortality among excessive drinkers was also associated with quantitative alcohol intake, diagnosed alcohol dependence (ICD-10 F10.2), and current smoking at assessment. ConclusionsPeople with chronic excessive alcohol intake experience decreased average survival but there is substantial variation in their mortality, with liver abnormality and alcohol dependence each associated with worse prognosis. Clinically, patients with these risk factors as well as high alcohol intake should be considered for early or intensive management. Research can usefully focus on the factors predisposing to dependence or liver abnormality.

BackgroundGabapentin and pregabalin have potential utility for treating alcohol use disorder (AUD), but their comparative effectiveness in reducing alcohol consumption in real-world settings is unknown. We compared changes in alcohol consumption associated with gabapentin or pregabalin treatment with those of matched unexposed comparators. MethodsWe identified patients who were prescribed gabapentin or pregabalin for [&ge;]60 days for any indication between 1 January 2009 and 30 June 2022 using electronic health records from the Veterans Aging Cohort Study (VACS-National). Alcohol consumption was measured using routinely-collected Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaires. We used propensity score matching to balance baseline characteristics between groups. Three comparisons were conducted: gabapentin vs. unexposed, pregabalin vs. unexposed, and pregabalin vs. gabapentin. Changes in AUDIT-C scores were estimated using multivariable difference-in-difference linear regression models. Analyses were stratified by baseline AUD diagnosis and AUDIT-C categories (lower-risk, at-risk, hazardous/binge). ResultsWe identified 592,957 gabapentin initiators, 14,923 pregabalin initiators, and 2,959,006 eligible unexposed comparators who were eligible for matching. Compared to unexposed individuals, patients who received gabapentin (DiD: 0.09, 95% CI 0.06, 0.11, p<0.0001) or pregabalin (DiD: 0.14, 95% CI 0.02, 0.26, p=0.0279) reported greater reductions in AUDIT-C scores. When compared head-to-head, pregabalin initiators reported greater reductions in AUDIT-C scores than gabapentin initiators with the largest difference observed among those with AUD (DiD: 0.86, 95% CI 1.22, 0.50, p<0.0001) and those who report baseline hazardous/binge drinking (DiD: 1.74, 95% CI 2.21, 1.27, p<0.0001). DiscussionIn this large, nationwide cohort, treatment with gabapentin and pregabalin were associated with reductions in reported alcohol consumption, compared to matched unexposed comparators. Initiation of pregabalin was associated with greater reductions than with gabapentin, particularly among those with AUD and those with highest severity of alcohol use. Known safety concerns and risk of misuse should be considered when prescribing these medications. Randomized clinical trials directly comparing these medications are necessary to validate these findings.

BackgroundThe UK has the fourth highest estimated prevalence globally of maternal alcohol consumption during pregnancy (41%). It is therefore important to understand the long-term impacts of prenatal alcohol exposure (PAE) by examining its impact on the development of adolescent multiple risk behaviours (MRBs) which may increase morbidity and premature mortality across the life-course. MethodsUsing Avon Longitudinal Study of Parents and Children (ALSPAC) cohort data with multiple imputation (n=6,752), we examined the impacts of infrequent, frequent, and binge PAE groups on the development of seven MRBs at 16 years old, encompassing substance misuse, risky sexual behaviour and antisocial behaviour. Data were analysed using multiple regression, using q-statistics to adjust for multiple comparisons. ResultsAdolescents with infrequent and frequent PAE were more likely to develop hazardous alcohol use at 16 years old compared to those without PAE, with the strongest association being for the frequent group (adjusted odds ratio (aOR) 1.45 [1.19-1.76], p<0.001, q-value=0.005). Adolescents exposed to binge drinking prenatally had an increased risk of engaging in underage sexual intercourse (aOR 1.34 [1.09-1.64], p=0.005, q-value=0.044). Binge drinking predicted a higher total MRB score (Coefficient = (+0.21 [+0.08 to +0.33], p=0.001, q-value=0.017). ConclusionsThis study supports the UK Chief Medical Officers Low Risk Drinking Guidelines that the safest approach if pregnant, or if there is a possibility of becoming pregnant, is to avoid drinking alcohol, with the more alcohol consumed during pregnancy the greater the risks of long-term harm to the baby. Given the findings that PAE may increase the risk of adolescent hazardous alcohol use and risky sexual behaviour, this study highlights the need for further research to understand the intergenerational effects of PAE.

BackgroundTobacco smoking rates in alcohol and other drug (AOD) treatment settings is much higher than in the general Australian population. As a result, people seeking treatment for AOD use experience a greater tobacco-related burden of illness. Attempts to reduce smoking rates in AOD treatment consumers have failed to identify smoking cessation strategies with long term effectiveness. The primary aim of this study is to examine the effectiveness of nicotine vaporised products (NVPs) or nicotine replacement therapy (NRT)on self-reported 6 months continuous abstinence at the 9-month follow-up (6 months following end-of 12 weeks of nicotine treatment) for people leaving smoke-free residential withdrawal treatment. Both groups will also receive Quitline telephone counselling. Secondary outcomes and process measures will also be collected. MethodsA two-arm, single-blinded, parallel-group randomised trial with a 6-month post-intervention follow-up (9 months following baseline) will be conducted. The setting is five residential and inpatient government-funded AOD withdrawal units across three cities in three states of Australia (New South Wales, Queensland, Victoria). Participants will be service users aged 18 years or over who smoked at least 10 cigarettes per day, interested in quitting in the next 30 days and have capacity to give informed consent. Research assistants will recruit participants during intake, who then complete a baseline survey, will be randomised to a condition, and receive their first Quitline call during AOD treatment. At discharge, all participants receive a discharge pack containing either NVPs or NRT, depending on condition allocation. DiscussionThis is the first study we know of that will be testing intervening with a tobacco smoking cessation approach during the transition phase from AOD treatment to community. From a public health perspective, this approach has the potential to have tremendous reach into a priority population for smoking cessation. Trial registrationAustralian and New Zealand Clinical Trials Registry (ACTRN12619001787178)

ImportanceA wide range of medications, non-combustible nicotine products, behavioural support, and alternative treatments are available in England to help people stop smoking. Understanding their effectiveness in the real world can support informed decision-making. ObjectivesTo provide up-to-date estimates of the prevalence and real-world effectiveness of different smoking cessation aids and explore moderation of effectiveness by socioeconomic position. DesignPopulation-based survey, 2006-2024. SettingEngland. Participants25,094 adults ([&ge;]16y) who reported having tried to quit smoking in the past year. Main outcomes and measuresThe outcome variable was self-reported continuous abstinence from the start of the most recent quit attempt up to the time of survey. Independent variables were use (yes/no) of the following aids in the most recent attempt: nicotine replacement therapy (NRT) obtained on prescription or over-the-counter; varenicline; bupropion; e-cigarettes; face-to-face behavioural support; telephone support; written self-help materials; websites; smartphone apps; hypnotherapy; Allen Carrs Easyway method; heated tobacco products (HTPs); nicotine pouches. Covariates included sociodemographic characteristics and features of the quit attempt. ResultsWe analysed data from 25,094 participants (mean [SD] age = 38.7y [15.3]; 48.5% women). In 2023/24, the most used aids were e-cigarettes (40.2%) and over-the-counter NRT (17.3%); 40.8% of quit attempts were unaided. While e-cigarette use was associated with higher odds of abstinence after adjustment for use of other aids and covariates (OR=1.95 [1.74-2.17]), use of over-the-counter NRT was not (OR=1.03 [0.93-1.15]). Other aids positively associated with abstinence were websites (used by 4.6% in 2023/24; OR=1.43 [1.03-1.98]), prescription NRT (4.5%; OR=1.33 [1.12-1.58]), varenicline (1.1%; OR=1.80 [1.50-2.18]), and HTPs (0.7%; OR=2.37 [1.24-4.51]). Face-to-face behavioural support (used by 2.2% in 2023/24) was also associated with higher odds of abstinence among those from less advantaged (OR=1.59 [1.19-2.14]) but not more advantaged social grades (OR=0.91 [0.65-1.29]). There was not clear evidence of a benefit of any other aid, although some analyses were inconclusive. Conclusions and relevanceA range of effective smoking cessation aids are available in England, but many people try to quit using less effective forms of support or none at all. Quit success rates could be improved by encouraging people to use more effective methods.

BackgroundParental smoking increases offspring smoking risk. Young people with mental health difficulties are more likely to have parents who smoke and start smoking themselves. Improving mental health in youth could help disrupt intergenerational cycles of nicotine use, but the extent to which depressive symptoms mediate the link between parental and offspring smoking remains unclear. MethodsWe used data on 6,729 participants of the Avon Longitudinal Study of Parents and Children (ALSPAC) with mother-reported data on parental smoking. Counterfactual-based mediation analysis was used to estimate both total and direct effects of parental smoking at offspring age 12 on offspring smoking at age 16 and estimate the indirect effect via offspring depressive symptoms at age 14. We also accounted for early offspring substance use (cigarettes, alcohol, or cannabis) at age 13. Multivariable logistic regression was used to examine pairwise associations between these variables. ResultsMediation analysis showed a total effect of parental smoking on offspring smoking (odds ratio [OR] = 1.44, 95% CI = 1.20-1.72). There was no indirect effect via depressive symptoms (OR = 1.00, 95% CI = 0.99-1.01) when adjusted for confounding. Regression analyses showed parental smoking was associated with early offspring substance use and later offspring smoking but not offspring depression. Early offspring substance use was associated with both offspring depression and later smoking. Higher depressive symptoms were associated with later smoking. ConclusionsParental smoking in early adolescence increases the odds of offspring smoking in later adolescence, but this does not appear to act through offspring depression.

Background and AimsThe physical, emotional, and social impacts of opioid abuse are well known; although preclinical models reveal the neurobiological pathways altered through opioid abuse, comprehensive assessments of gene expression in human brain samples are lacking. The goals of the present study were to compare gene expression in the prefrontal cortex between brain samples of individuals who died of acute opioid intoxication and group-matched controls, and to test if differential gene expression was enriched in gene sets related to opioid use. DesignCross-sectional study using human brains donated to the Lieber Institute for Brain Development. Study groups included 72 brain samples from individuals who died of acute opioid intoxication, 53 group-matched psychiatric control samples, and 28 group-matched normal control samples. SettingMaryland, USA. ParticipantsPostmortem tissue samples of the dorsolateral prefrontal cortex from 153 deceased individuals (Mage = 35.42, SD = 9.43 years; 62% male; 77% White). MeasurementsWhole transcriptome RNA sequencing was used to generate exon counts, and differential expression was tested using limma-voom. Analyses controlled for relevant sociodemographic characteristics, technical covariates, and cryptic relatedness and batch effects using quality surrogate variable analysis. Gene set enrichment analyses (GSEA) also were conducted. FindingsSixteen genes were differentially expressed (i.e., FDR-corrected p < .10) in opioid samples compared to control samples. The top differentially expressed gene, NPAS4 (FDR adjusted p = .005), was downregulated in opioid samples and has previously been implicated in cocaine use. Enrichment analyses did not provide evidence for enrichment in pathways obviously related to opioid use. ConclusionsNPAS4 is differentially expressed in the prefrontal cortex of subjects that died of an opioid overdose, providing evidence for another gene with functional relevance to opioid use and overdose.

Withdrawal statementThe authors have withdrawn this preprint because peer review resulted in substantial changes to analysis methods, outcomes, and interpretation. Hence the final peer-reviewed version is substantially different from this preprint. Therefore, the authors do not wish this work to be cited as reference for the project. Please instead see the peer-reviewed version available at http://doi.org/10.1111/add.70184 and if you have any questions, please contact the corresponding author.

BACKGROUNDO_ST_ABSObjectiveC_ST_ABSTo examine birth weight change caused by adding financial rewards for smoking cessation compared to no rewards for pregnant women. To estimate the average expected birth weight change for those who quit because of rewards. METHODSThis study updates a previous systematic review and refocuses the outcome from smoking cessation to birth weight. Eligibility CriteriaTrials with an experimental design allowing treatment effects to be attributed to rewards were included. Trials involving non-pregnant participants, or with no report of magnitude, treatment duration, timing or where most rewards were contingent on another behaviour (e.g., treatment attendance) were excluded. Information sourcesMedline, PsycInfo, Embase, Cochrane (Central Register of Controlled Trials, Tobacco Addiction Group Specialised Register and Database of Systematic Reviews), and PubMed searched to 5th December 2023. Risk of biasRisk of bias and certainty of evidence used Cochrane Risk of bias 2 and GRADE assessments. Synthesis of resultsPrimary analysis estimated Intention-To-Treat (ITT) mean birthweight difference when randomised to offer of rewards versus control. Within-trial estimates and standard errors were derived from mean, standard deviation, and sample size data provided, or from publications. Pooled ITT estimates used common (fixed) and random effects models. Secondary analyses used trial team supplied data to derive Complier Average Causal Effect (CACE) estimate of smoking cessation on birth weight, and a standard error. Estimates were pooled using common and random effects models. Similar analyses were applied to low birth weight (<2500g), birth weight for gestational age z-scores, and small for gestational age (<10th percentile). RESULTS Included studiesPrimary analysis included 8 trials (2351 participants) from the UK (2 trials, 1475 participants); France (1 trial, 407 participants), and the US (6 trials, 469 participants). Secondary analysis included 7 trials as data retrieval from one US trial (51 participants) was not possible. Synthesis of resultsPrimary ITT analysis (2351 participants) estimated a mean 46.3g (95% CI: 0.0 to 92.6) birth weight increase when offered financial rewards for smoking cessation. Secondary CACE analysis (2239 participants) estimated a mean 206.0g (95% CI: -69.1 to 481.1) increase for smokers who quit because of rewards. There was no effect on low birth weight (<2500g), or birth weight adjusted for gestational age, though less babies were born small for gestational age, particularly if cessation was because of rewards (CACE risk difference -17.7%; 95% CI: -34.9% to -0.4%). DISCUSSION Limitation of evidenceSample size led to imprecision - maximum 2351 participants. A single trial of 3712 participants would give 80% power at 5% significance to show a 46g increase from 3.1kg to 3.146kg with 0.5kg standard deviation in both groups. Consistency - trials where smoking cessation increased (7 of 8) all showed a mean birth weight increase. In one trial smoking cessation fell as did birth weight. Bias is unlikely as 3 of 4 trials with no birth weight data showed increased cessation consistent with higher mean birth weight. InterpretationTrials of contingent financial rewards for smoking cessation have previously been shown to more than double pregnancy quit rates. We have uncovered a significant (46g) population level increase in mean birth weight, driven by a clinically important mean increase (206g) for those who quit because of financial rewards associated with a reduction in Small for Gestational Age births. OTHER FundingReview update - The U.S. National Institute of Health, National Institute of General Medical Sciences Center of Biomedical Research Excellence Award P30GM149331. Data retrieval, synthesis and analysis - Scottish Cot Death Trust. Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024494262

BackgroundGlucagon-like peptide 1 receptor agonists (GLP-1 RAs) have shown promise for alcohol use disorder (AUD). ObjectiveTo evaluate the association between use of newer GLP-1 RAs (semaglutide, tirzepatide) and alcohol-related hospitalizations among adults with AUD and either type 2 diabetes (T2D) or obesity. MethodsThis retrospective target trial emulation study used electronic health record data from Truveta to identify adults with AUD and either T2D or obesity, who initiated a newer GLP-1 RA (semaglutide, tirzepatide) or relevant active comparator between 2018 and 2024. Four target trials were constructed to reflect clinically distinct populations and comparators: (1) ADM trial (patients with T2D and comparators of other anti-diabetic medications [ADM]), (2) AOM trial (patients with obesity but not T2D and comparators of other anti-obesity medications [AOM]), (3) MAUD-T2D trial (patients with T2D and markers of more severe AUD and comparators of medications for alcohol use disorder [MAUD]), (4) MAUD-obesity trial (patients with obesity, no T2D, and markers of more severe AUD and comparators of MAUD). The primary endpoint was time to alcohol-related hospitalization. Non-alcohol-related hospitalization served as a negative control outcome. Propensity score-based methods (weighting and matching) were used to control for confounding. Cox proportional hazards models were used to estimate the treatment effect of newer GLP-1 RA in four target trials. ResultsA total of 40,260 patients were identified, including 18,515 in the ADM trial, 9,256 in the AOM trial, 9,975 in the MAUD and T2D trial, and 11,039 in the MAUD and obesity trial. GLP-1 RAs were associated with a lower hazard of alcohol-related hospitalization in the ADM (HR [95% CI]: 0.70 [0.59 - 0.83] vs. sulfonylureas; 0.73 [0.62 - 0.86] vs. other ADMs), AOM (HR: 0.59 [0.48 - 0.74]), MAUD-T2D (HR: 0.36 [0.29 - 0.46]), and MAUD-obesity (HR: 0.32 [0.23 - 0.43]) trials. No significant differences were observed for non-alcohol-related hospitalizations for ADM and MAUD-T2D trials. ConclusionNewer GLP-1 RAs were associated with reduced risk of alcohol-related hospitalization across clinically distinct populations.

BackgroundAlcohol Use Disorder is associated with suicide and suicide attempts, and addiction treatment services have a role in suicide prevention. We aimed to identify risk factors for suicide attempt among a cohort of community-based alcohol treatment service users. MethodsLinked data from 4415 adults accessing secondary addiction services for alcohol treatment between 2006 and 2019 in London, UK, were used to identify risk factors for suicide attempt. Cox proportional hazards regression estimated the relative increase or decrease in hazard associated with each risk factor on a composite outcome event; death by suicide or contact with emergency psychiatric care within one year of starting treatment. FindingsThere were 468 (10.5%) crisis care contact events, and <10 suicide deaths. After adjustment, factors associated with increased hazard of crisis care contact or death by suicide were history of suicide attempt (HR 1.83[1.43-2.33]), poor mental health (HR 1.81[1.41-2.32]), current suicidal ideation (HR 1.65[1.18-2.31]), use of drugs other than cocaine, cannabis and opiates (HR 1.41[1.02-1.95]), female sex (HR 1.34[1.10-1.65]) and social isolation (HR 1.24[1.02 - 1.51]). Factors associated with reduced hazard of crisis care contact or death by suicide were alcohol abstinence (HR 0.51[0.31-0.83], ref>30 units), drinking 1-15 units (HR 0.64[0.49-0.85], ref>30 units), Black ethnicity (HR 0.61[0.45-0.83]) and living with children (HR 0.74[0.56-0.99]). InterpretationThe identified risk factors for suicide attempt can help risk formulation and safety planning among patients accessing alcohol treatment services. FundingNational Institute for Health Research Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, Kings College London. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSAlcohol Use Disorder (AUD) is a risk factor for suicide and suicide attempt, and among people with AUD those accessing addiction treatment services are particularly at risk. Effective suicide risk formulation and safety planning requires an understanding of the demographic, clinical and circumstantial factors that are associated with increased or decreased risk of suicide attempt in the population of people accessing treatment for their alcohol use. We searched PubMed using search terms ((("alcohol use disorder") OR ("alcohol depend*") OR ("substance use disorder") AND (("treat*") OR ("service*"))) AND (("suicide attempt") OR ("suicid*"))) as well as Google Scholar and cited reference searching in Web of Science, to identify previous studies of risk factors for suicidal behaviour in cohorts engaged with some form of Substance Use Disorder (SUD) treatment which included alcohol at least to a minimal degree, and which measured a suicide-related outcome after treatment commencement. The impact of the risk factors identified in these studies varied greatly, reflecting heterogeneity in the substance use profiles and settings of the samples used. We found no longitudinal studies which consider risk factors for suicidal behaviour in a purely alcohol-using sample accessing community-based addiction care. The single consistent risk factor for suicidal behaviour across these studies was a previous history of suicide attempt. Added value of this studyOur study uses 14 years worth of structured data from service users accessing Community Drug and Alcohol Team (CDAT) treatment primarily for their alcohol use. A range of risk factors for suicide attempt (measured via contact with crisis care services) or death by suicide in the year following treatment start were identified: predisposing factors included a history of suicide attempt, female sex and White ethnicity; modifiable factors included social isolation, poor mental health, current suicidal ideation or carer concern, and use of drugs other than cocaine, cannabis and opiates; protective factors included abstinence from or relatively low use of alcohol, and children living with the service user. This is the first prospective analysis of risk factors for suicidal behaviour in a purely alcohol-using sample accessing community-based addiction care. This population represent the largest proportion of CDAT service use, with a uniquely elevated suicide risk. Implications of all the available evidenceA wide range of risk factors for suicide and suicide attempt can be identified among people accessing alcohol treatment, providing population-specific contextual knowledge that can aid patient-centred suicide assessment and safety planning, and a potential framework within which potential avenues for intervention can be identified.

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.

Background & AimsLower risk guidelines for safer levels of cannabis use could help to reduce the health burden posed by cannabis use disorder (CUD). We aimed to estimate risk thresholds for CUD based on delta-9-tetrahydrocannabinol (THC) consumption using standard THC units (1 unit = 5mg THC). DesignData from the CannTeen study, a longitudinal observational study consisting of five assessments over a 12-month period. SettingLondon, UK. ParticipantsParticipants were n = 65 adults aged 26-29 (46% female, 70.77% white ethnicity) and n = 85 adolescents aged 16-17 (56% female, 65.48% white ethnicity). All participants reported at least one use of cannabis during the 12-month study period and completed an assessment of DSM-5 CUD symptoms at the final follow up. MeasurementsMean weekly standard THC units were estimated using the Enhanced Cannabis Timeline Followback, a comprehensive assessment of quantity, frequency and potency of cannabis consumed. This was administered at 3-month intervals and averaged over a 12-month period. Past 12-month diagnosis of DSM-5 CUD was assessed at the final follow-up. Receiver operating characteristic curve models estimated the extent to which weekly standard THC unit consumption could discriminate no CUD from any CUD (mild, moderate, or severe), and no CUD from moderate/severe CUD, in adults and adolescents separately. Risk thresholds were selected based on cut-offs that maximised sensitivity and specificity. FindingsDiscrimination accuracy of weekly standard THC units on CUD was good, with area under the curve > 0.70 for all models. Optimal cut-offs for risk of any CUD (versus no CUD) were 8.26 units per week for adults and 6.04 units per week for adolescents. For risk of moderate/severe CUD (versus no CUD) optimal cut-offs were 13.44 units per week for adults and 6.45 units per week for adolescents. ConclusionsStandard THC units show good discrimination accuracy of CUD at different severities and in different age groups. Safer levels of cannabis use, defined by low weekly standard THC unit consumption, could be recommended in lower risk cannabis use guidelines.