Individuals with opioid use disorder (OUD) frequently present with co-occurring mental health conditions such as depression and posttraumatic stress disorder (PTSD), along with other mental health substance use disorders, physical health conditions and social determinants that together comprise 'clinical complexity.' Collaborative care (CC), a primary care-based behavioral health integration model, aims to improve outcomes through coordinated, patient-centered treatment. This study examined heterogeneity in baseline clinical complexity among participants in the CLARO (Collaboration Leading to Addiction Treatment and Recovery from Other Stresses) trial and assessed whether the effects of CC versus enhanced usual care (EUC) differed across clinical complexity groups. Secondary analysis of CLARO, a pragmatic randomized clinical trial (n = 797) of CC versus EUC for adults with OUD and depression and/or PTSD, conducted in 18 low-resourced primary care clinics in New Mexico and California, USA. Latent class analysis of baseline data identified subgroups defined by mental health and substance use as the main characteristics along with physical health and social challenges. Six-month treatment effects were estimated using one-step models that jointly estimated latent class membership and class-specific outcomes, incorporating class × treatment interactions. Outcomes included depression symptom severity, PTSD symptom severity, and buprenorphine utilization and prescribing duration. Three subgroups were identified: (1) low complexity (43%), with relative clinical and social stability; (2) mental health complexity (34%), with high psychiatric symptoms but lower substance use and moderate social adversity; and (3) high dual complexity (23%). Compared with EUC, CC was associated with lower depression severity at follow-up for the low-complexity class, but not for other classes. CC and EUC did not differ statistically significantly with respect to PTSD outcomes in any class. Buprenorphine utilization and prescribing duration outcomes were similar across CC and EUC treatment arms. The effects of collaborative care may vary according to patients' baseline clinical complexity. Collaborative care appears to be associated with more favorable depression outcomes than enhanced usual care among participants with lower clinical complexity but not among those with higher clinical complexity.
Mindfulness-based relapse prevention (MBRP) has been shown to be beneficial to individuals with substance use disorder (SUD) in the West. The current pilot study aimed at testing the feasibility of MBRP in a Chinese population. This pilot study adopted a design of randomized controlled trial comparing MBRP with treatment-as-usual group (TAU). Participants were recruited from residential detox centers, community addiction counseling centers and substance abuse clinics specialized addiction treatment clinics in Hong Kong. A total of 81 adults (85.2% male) with SUD (illicit drugs only) were recruited. The intervention group participants (n = 41) attended a 1-hour orientation session followed by 2-hour weekly MBRP sessions for 8 weeks, delivered by a qualified MBRP teacher. The TAU group participants (n = 40) continued their service received from their referral agency. (After completion of all study assessments they were offered the same 8-week MBRP course.) MEASUREMENTS: Feasibility was measured by attendance, course satisfaction and retention rate. Participants' change in substance use and other related outcomes were captured by self-reported drug use, urine drug tests and a list of psychometric scales at baseline, immediately after MBRP and 3- and 6-month follow-up. The MBRP course satisfaction was high, and the attendance (57.4%) and retention rates (63.4%-85.4%) were comparable to previous trials. No statistically significant differences were observed between the MBRP and TAU groups for any outcomes, including craving, depression, anxiety, mindfulness and health-related quality of life; however, improvement trends were noticed in the MBRP group in self-efficacy in managing high-risk situations at post intervention, as well as in addiction severity and psychological flexibility at the 6-month follow-up. Mindfulness-based relapse prevention was shown to be feasible for substance use disorder treatment in a Chinese population. In this small study there was only limited evidence of abstinence efficacy, and no evidence of a benefit on other secondary outcomes.
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Gambling-related harm is not concentrated solely among individuals meeting criteria for problematic or disordered gambling. Tackling harm at a population level is essential to reducing the total burden of harm and preventing escalation to more severe harms. The public health approach to gambling recognises this and the need to address both individual and systemic factors that shape people's risk of harm. Despite this, research and policy in the field remain largely focused on interventions that target individual responsibility, such as educational messages, warnings, and voluntary tools. Chater and Loewenstein's i-frame (individual-frame) and s-frame (system-frame) distinction provides a compelling basis for reorienting gambling harm prevention efforts. I-frame interventions target individual decision-making and self-regulation, while s-frame interventions seek systemic changes through restrictions and structural reforms. This paper argues that s-frame approaches are better suited to preventing gambling harms, particularly lower-level harms at the population level, because they [1] do not rely on individuals to recognise and effectively navigate the complex mathematical properties and potentially misleading features inherent in many gambling products, [2] apply universally without requiring individual engagement, and [3] can counter commercial interests without depending on consumer self-restraint. Reframing gambling harm prevention through the i-/s-frame lens offers conceptual clarity, highlights the opportunity costs of an overreliance on individual-focused interventions, and exposes incentives that perpetuate the status quo. This paper explains why i-frame approaches have dominated to date and how we can make the shift towards the s-frame. Rather than abandoning i-frame approaches, research priorities should be rebalanced toward understanding, implementing, and evaluating systemic solutions. While i-frame interventions remain valuable for individuals seeking help, preventing population-level harms requires proportionate investment in structural solutions that make gambling products safer by design.
In a randomised open-label trial among hospitalised patients with atherosclerotic vascular disease, motivational smoking cessation counselling with proactive referral to community-based follow-up was more effective than brief cessation advice and written information, with 6-month continuous abstinence rates of 49.5% vs. 24.5%. This study aimed to estimate the cost-effectiveness of this intervention compared with brief cessation advice. Economic evaluation alongside a multicentre, randomised open-label, blinded-endpoint trial with 1:1 randomisation. Three secondary care hospitals in Norway. Recruitment took place from November 2021 to October 2023. Hospitalised patients aged 18 years or older with established atherosclerotic vascular disease who reported smoking at least one cigarette daily before admission were eligible for participation, regardless of whether admission was planned or unplanned. A total of 221 patients were randomised. One participant withdrew informed consent and was excluded from all analyses, leaving 220 participants in the economic evaluation. The cohort comprised 40% women and the mean age was 65.2 years. Intervention costs included staff training, materials and personnel time. Hospital costs during the 16-month follow-up were estimated using Diagnosis-Related Group cost weights. Survival beyond follow-up was extrapolated using national mortality data adjusted for age, sex and atherosclerotic vascular disease. Lifetime costs were estimated using mean costs from the final six months of follow-up. The primary economic outcome was net monetary benefit (NMB), calculated at a willingness-to-pay threshold of €38 346 per life-year gained. The incremental cost-effectiveness ratio was also estimated. Future costs and life-years were discounted at 4%. Uncertainty estimates (UE) were obtained using bootstrapping. During the 16-month follow-up, five patients (4.6%) died in the intervention group and nine (8.1%) in the control group. Discounted life expectancy from baseline was 13.54 years in the intervention group and 12.47 years in the control group, corresponding to an incremental gain of 1.06 life-years (95% UE = -0.72 to 3.31). The incremental discounted lifetime cost was €3280 per patient (95% UE = -€19 457 to €26 436), resulting in an incremental cost-effectiveness ratio of €3094 per life-year gained. At a willingness-to-pay threshold of €38 346 per life-year gained, the NMB was €37 475 (95% UE = -€15 868 to €107 797) and the probability of the intervention being cost-effective was 90.5%. Motivational smoking cessation counselling delivered during hospitalisation with proactive referral to community-based follow-up had a high probability of being cost-effective from a hospital perspective for patients with atherosclerotic vascular disease.
Increased risk of alcohol dependence is recognised following bariatric surgery. Modified gastrointestinal anatomy and neurohormonal profiles lead to altered alcohol metabolism, peak blood alcohol concentrations and enhanced reward circuits and cravings. For patients with metabolic associated fatty liver disease, bariatric surgery has been shown to reduce liver fibrosis; however, the impact of bariatric surgery on alcohol consumption and consequent liver fibrosis has not been well-characterised using validated measures. This study examined the changes in alcohol consumption patterns, alcohol dependence and validated liver fibrosis measures before and after bariatric surgery. A retrospective cohort study assessing patients seeking treatment for alcohol problems with a history of gastric sleeve (GS) or Roux-en-Y Gastric Bypass (RYGB) in a quaternary hospital in Brisbane, Australia. Validated measures of alcohol dependence [Alcohol Use Disorders Identification Test (AUDIT) and brief Michigan Alcohol Screening Test (bMAST)] and non-invasive liver fibrosis (FIB4 and APRI) were compared pre- and post-surgery. Twenty patients were identified with prior GS and 10 patients with RYGB. Following bariatric surgery, body mass index was reduced by 14.5 (±9.39) kg/m2. Metabolic co-morbidities were less frequent post-surgery. Pre-surgery, the mean AUDIT score was 10.2 ± 8.9, with 9 patients having scores indicative of alcohol dependence. Mean AUDIT increased statistically significantly post-surgery (18.1, standard deviation ±11.4; P < 0.001) with 29 patients meeting criteria for alcohol dependence. AUDIT components relating to both consumption (volume, frequency) and harmful consequences of alcohol increased following surgery. Despite surgery lowering metabolic liver fibrosis risk, worsened liver fibrosis was observed [mean FIB4 (0.98 ± 1.8) and APRI (0.41 ± 0.83) increased; P < 0.05]. Within a cohort of adults seeking treatment for alcohol problems, increases in alcohol consumption and alcohol-related harm were observed following bariatric surgery. Despite improvement in risk factors for metabolic-associated fatty liver disease after surgery, non-invasive markers for hepatic fibrosis worsened, likely in the setting of harmful alcohol intake and associated liver injury. This supports the role of bariatric surgery pre-operative assessment and post-operative follow-up to identify and manage alcohol-related problems and associated liver disease risk.
Current medications for alcohol use disorders (AUD) are under-used and of moderate benefit; new or improved treatments are much needed. Preclinical and small clinical studies indicate that pioglitazone, a thiazolidinedione agonist of the peroxisome proliferator-activated receptor gamma, may reduce alcohol use. The primary purpose of this study was to evaluate, in a randomized trial, the effect of pioglitazone on alcohol use and craving in adults with AUD. A double-blind, placebo-controlled randomized trial. Enrollment occurred in the United States at two Veterans Affairs Health Care Centers (VAHCS) from July 2019 to March 2024. One hundred eighty-five Veteran men and women older than 18 years with at least a moderate AUD and current alcohol use. Oral pioglitazone was given at dosages of 0 (placebo) (n = 92), or 45 mg (n = 93) over 14 weeks. All participants received Brief Behavioral Compliance Enhancement Treatment at each visit. The primary outcome measure was the number of heavy drinking days during week 14 as measured by the Timeline Follow Back (TLFB). Secondary measurements included the number of standard drinks consumed per week, the rate of no heavy drinking days over the last 8 weeks of the study, alcohol craving, anxiety, depression and post-traumatic stress disorder symptoms. Exploratory outcome included change in alcohol use based on inflammation (C-reactive protein) at baseline. There was no difference between groups on the primary outcome (pioglitazone mean = 2.43, placebo mean = 2.01, difference = 0.43, 95% confidence interval = -0.25 to 1.10, P = 0.22). No differences were found between groups in secondary alcohol use measures or a measure of craving. Participants with elevated inflammation at baseline treated with pioglitazone had a greater decrease in heavy drinking days over time compared with placebo (z = 2.21, P = 0.03). Pioglitazone was safe and well tolerated. Pioglitazone administered to people with alcohol use disorder at a dose of 45 mg per day appears to be safe although there is no evidence that it is efficacious in reducing alcohol use, alcohol craving or any psychiatric measures.
Substance use disorders are associated with an elevated risk of self-harm. Currently, clinical and structured assessment of self-harm risk typically relies on evidence from the general population samples. The aim of this study was to develop a risk model for self-harm that incorporates predictors specific to individuals with substance use disorders. Using national registers, we identified a population-based cohort of 449 720 individuals with substance use disorders in Sweden between 2006 and 2020. We tested independence and strength of a range of socio-demographic and clinical factors, obtained through linkage of population-based registers, with a Cox proportional hazards model, and estimated the risk of self-harm. For the risk model, 361 120 individuals were allocated to the development sample and 88 600 to external validation based on different geographical regions. We assessed self-harm risk over five predetermined follow-up periods-within 7 days, 1 month, 3 months, 6 months and 12 months-following a healthcare contact for substance use disorders. In the development sample, self-harm rates ranged from 0.6% to 3.5%, and in the validation sample from 0.5% to 3.6%. Ten risk factors were retained in the final risk model. Strongest associations with subsequent self-harm were for clinical factors: previous self-harm [hazard ratio (HR) = 3.17, 95% confidence interval (CI) = 3.08-3.26] and comorbidity of mental disorders (HR = 2.63, 95% CI = 2.50-2.72). Recent psychotropic medication use, including antidepressant (HR = 1.29, 95% CI = 1.23-1.38) and antipsychotic treatments (HR = 1.34, 95% CI = 1.24-1.44), was associated with increased risk, even after adjusting for psychiatric comorbidity, likely reflecting greater clinical severity and complexity. Across follow-up periods, performance was good in terms of discrimination, with area under the curve (AUCs) ranging from 0.73 (95% CI = 0.71-0.76) to 0.79 (95% CI = 0.78-0.80). In relation to calibration, expected-to-observed risk ratios were 1.00 to 1.04 and Brier scores 0.01 to 0.04 across follow-up periods. We used the model to generate a simple web-based risk calculator [Oxford Self-hArM after substance use disorders (OxSAMS)]. Modifiable clinical factors appear to have the strongest associations with increased risk of self-harm in people with substance use disorders. Structured tools, taking account of the different strengths of those factors, could inform clinical decision-making and provide a baseline assessment for training and research.
Opioid use disorder (OUD) treatment guidelines worldwide recommend opioid agonist treatment (OAT) as a long-term, potentially indefinite treatment for managing OUD. However, many individuals express a strong interest in eventually tapering fully off treatment. Current clinical practice guidelines offer relatively limited guidance or evidence on the appropriate timing to initiate a taper. We aimed to determine the safety and comparative effectiveness of different times from completion of OAT induction at which tapering could be considered to maximize the likelihood of taper completion and minimize the risk of mortality. Population-based retrospective observational study and target trial emulation based on nine linked administrative health databases. British Columbia, Canada, from 1 January 2010 to 17 March 2020. Individuals (identified via linkage of nine provincial health administrative databases) completing OAT induction with methadone or buprenorphine/naloxone who were ≥18 years of age with no known pregnancy, no history of cancer or palliative care and not currently incarcerated. We executed both incident-user (no OAT experiences) and prevalent-new-user (no OAT within the past month) analyses. The time between completed OAT induction and taper initiation: <3 months, 3-6 months, 6-12 months, compared with 12-48 months. The primary outcomes were completed taper (reaching a final daily dose of ≤5 mg/day for methadone, or ≤2 mg/0.5 mg/day for buprenorphine/naloxone) and all-cause mortality. A clone-censor-weight approach was used to adjust for informative censoring and balance baseline characteristics between the groups. Logistic regression and pooled logistic regression models were used to estimate odds ratios (ORs) for completed taper and hazard ratios (HRs) for all-cause mortality, respectively, each with 95% compatibility ('confidence') intervals. We included 17 726 incident users (buprenorphine/naloxone: 36.9%) and 49 515 treatment episodes (buprenorphine/naloxone: 31.2%) from 31 231 prevalent new users who completed induction in the analyses. Among prevalent new users, beginning tapering within 3 months, between 3 and 6 months and between 6 and 12 months of completing induction was associated with an increased likelihood of completed taper [methadone: <3 months: adjusted odds ratio (aOR) = 3.09, 95% compatibility interval (95% CI) = 2.58-3.68; buprenorphine/naloxone: <3 months: aOR = 6.90, 95% CI = 5.19-9.16] but a higher risk of mortality [methadone: <3 months: adjusted hazard ratio (aHR) = 1.18, 95% CI = 1.12-1.25; buprenorphine/naloxone: <3 months: aHR = 1.12, 95% CI = 1.05-1.19], compared with initiating a taper between 12 and 48 months. Similar results were found among incident users. Although initiating early tapering off opioid agonist treatment may be associated with a greater likelihood of taper completion, this practice also increases the risk of mortality.
We evaluated whether community-level naloxone distribution, medication for opioid use disorder treatment and retention and incident high-risk opioid prescribing rates were associated with opioid overdose death rates. Observational cohort conducted using 2019 to 2023 community-level data as an exploratory analysis of the HEALing (Helping to End Addiction Long-term®) Communities Study (HCS). Exposures included: (1) community-level naloxone distribution, past 12-months, categorized as ≤1000 units per 100 000 population vs. 1001-3000 units per 100 000 population vs. >3000 units per 100 000 population; (2) individuals treated with buprenorphine per 100 000 adult population in the current quarter; (3) individuals retained on buprenorphine for ≥ 180 days per 100 000 adult population in the current quarter; and (4) incident high-risk opioid prescribing per 100 000 adult population in the current quarter. Population-based study of 67 communities with 8.2 million adults in Kentucky, Massachusetts, New York and Ohio, USA, with required annual opioid overdose death rates of > 25 per 100 000 adult population and at least 30% rural. Across the 67 communities participating in the HCS, the adult population was 31% 18-34 years, 31% 35-54 years, 38% 55 years and over, 52% female, 73% non-Hispanic White, 15% non-Hispanic Black and 7.4% Hispanic. Quarterly community-level opioid overdose death rates from 2020 through 2023. The 2019 annual rates were 40.4 opioid overdose deaths, 1287 naloxone rescue units distributed, 977.7 people received buprenorphine treatment, 546.3 people retained for more than 180 days on buprenorphine and 1266.7 high-risk opioid prescribing incidents per 100 000 population. In models adjusted for state, community age, sex, race/ethnicity, rurality, HCS intervention group assignment, 2019 rates of opioid overdose death, naloxone distribution, buprenorphine and high-risk opioid prescribing, and the ratio of opioid overdose deaths involving fentanyl, an increase in 100 people treated with buprenorphine per 100 000 population was associated with a decrease of 0.92 [95% confidence interval (CI) = -1.30 to -0.55] in the quarterly opioid overdose death rate, while an increase of 100 people retained on buprenorphine for more than 180 days per 100 000 population was associated with a decrease of 1.3 (95% CI = -1.8 to -0. 76). There were no statistically significant associations between naloxone distribution or incident high-risk opioid prescribing with change in quarterly opioid overdose death rates. In this exploratory analysis, increases in both buprenorphine treatment and retention were statistically significantly associated with decreases in opioid overdose death rates, after adjusting for baseline rates of buprenorphine treatment and retention.
Originally developed for clinical screening for hazardous alcohol use, the Alcohol Use Disorder Identification Test - Consumption (AUDIT-C) is also widely used in epidemiological research and monitoring. However, its cutoff values may not suit all purposes, and evidence on its predictive validity is limited. We examined how AUDIT-C scores relate to subsequent register-based alcohol-attributable events across age and sex and identified optimal thresholds for predicting these outcomes. Five general population surveys conducted in 2011-2017, linked to nationwide registers with follow-up until the end of 2023 (total follow-up 879 964 person-years). Nationwide, Finland. Adults aged ≥20 years (n = 103 567). AUDIT-C to assess exposure. incident alcohol-attributable events in any of the registers capturing care, deaths and prescription medicines (n = 1444). The hazard of register-based alcohol-attributable events increased approximately exponentially with increasing AUDIT-C score. It rose more strongly among women than men [hazard ratio (HR) = 1.61, 95% confidence interval (CI) = 1.55-1.67 for women; HR = 1.45, 95% CI = 1.40-1.49 for men; P < 0.001 for the sex × AUDIT-C interaction]. The risk of alcohol-attributable events was statistically significantly raised at 2 points among women and 3 points among men with 1 point as a reference level. The suggested optimal cutoff values were 2 points for women aged ≥80, 3 points for women aged 65-79 and men aged ≥80, 5 points for women aged 20-64 and men aged 65-79 and 6 points for men aged 20-64. Using Alcohol Use Disorder Identification Test - Consumption (AUDIT-C) scores, optimal cutoff values for predicting alcohol-attributable harm may differ by age and sex, with lower cutoffs for older individuals and women. The ≥65 age group appears to be heterogeneous with regard to vulnerability to alcohol-attributable harm, which should be considered when establishing cutoffs or guidelines for alcohol use.
Early initiation to cannabis use in adolescence is linked to cognitive and mental health risks. Having friends who use cannabis is a strong risk factor for initiation, but the mechanisms underlying this relationship are unclear. This study examined the role of perceived ease of access to cannabis in the association between close friends' cannabis use and cannabis initiation. Observational longitudinal investigation using data from the COMPASS study. A convenience sample of 11 high schools in Québec, Canada, from 2017 to 2019. 1768 students who had not initiated cannabis use before 2019. Having ≥1 close friend who uses cannabis and perceived ease of access to cannabis were measured in 2018, while cannabis initiation in the past 12 months was assessed in 2019. Covariates measured in 2017 included sociodemographic factors, substance use history, lifestyle behaviors and school-related variables. We compared the risk of cannabis initiation across groups defined jointly by friends' cannabis use and perceived access. Generalised estimating equations with bootstrap resampling, inverse probability weighting for attrition and multiple imputation for missing data were used to estimate these associations. Natural effect models were then applied to estimate total, direct and indirect effects with initiation as the outcome and perceived access as the mediator. Within the COMPASS cohort, 14% of cannabis-naive adolescents in 2018 initiated use in 2019. Using students with no close friends who use cannabis and who perceive access as difficult as the reference group, the risk difference (RD) for having at least one friend who uses cannabis while still perceiving access as difficult was 3.2 [95% confidence interval (CI) = -3.8 to 10.2]. Perceiving access as easy but having no friends who use cannabis yielded an RD of 8.4 (95% CI = 3.0-13.7). Friends' cannabis use combined with easy access acted synergistically, producing an RD of 21.6 (95% CI = 15.5-27.7). According to the natural effect models, perceived ease of access mediated about 39% of the association between having ≥1 close friend who uses cannabis and subsequent initiation, suggesting a possible explanatory pathway. In Canada, cannabis initiation risk appears to be highest among adolescents with both exposure to close friends who use cannabis and perceived easy access. Perceived access may help explain part of this association. Preventive strategies should address the influence of friends and accessibility through school policies, public education and stricter enforcement of access restrictions to delay adolescent cannabis use.
A minimum unit price (MUP) of AUD$1.30 per standard drink was implemented in 2018 in the Northern Territory (NT), Australia, to reduce the availability of cheap alcohol. Despite evidence of its efficacy in decreasing alcohol consumption and harms, the MUP was repealed on 1 March 2025. This study aimed to determine the immediate impacts of the MUP repeal on the price of off-premises (i.e. takeaway) alcohol in Darwin, NT, assessing the proportion of products available <$1.30 per standard drink after the repeal in March 2025, identifying whether these products were pre-existing or new to market, and analysing any broader shifts in the price distribution across all alcoholic products that could be attributable to the repeal. Observational study of all alcoholic products available from three large alcohol retailer websites. Darwin, NT, between October 2024 and March 2025. Price per standard drink was estimated, and fixed-effects panel quantile regression was used to test for price differences. Within one month of the repeal, no beer or spirits, 5.1% of all wine and 2.5% of all ciders were available <$1.30 per standard drink, including 67.6% of the 37 wine products in vessels ≥1 L. Of the products identified at <$1.30 per standard drink, most had been available in previous months (i.e. not new or restocked). Quantile regression results showed a downward shift in price across the market for all product types, including beer and spirits, which were priced substantially above the $1.30 threshold at all percentiles. The largest reductions were observed for cheaper spirits, beer, cider and wine ≥1 L, ranging from $0.08 at the 20th percentile for spirits to $0.48 for wine ≥1 L at the 10th percentile. The minimum unit price repeal in Northern Territory, Australia, in March 2025 resulted in an immediate increase in the availability of cheap alcohol products and a downward shift in the overall price of alcohol in the off-premises market, particularly for lower-priced products.
Understanding key product characteristics of oral nicotine pouches (ONPs), an emerging nicotine product category, is essential to developing evidence-based regulations that address ONP use among young populations. This experimental trial assessed the effects of variations in nicotine concentration and pH in NPs on two behavioral outcomes of regulatory interest: sensory attributes and appeal. We conducted an in-person, double-blind, within-subject randomized experiment involving standardized self-administration of 4 commercially available NPs (drawn from a pool of 20 ZYN and on! products) varying in nicotine strength (high: 6-8 mg vs. low: 3-4 mg) and pH (high: 8.5-9.3 vs. low: 7.6-8.0). Experimental conditions were not mutually exclusive (i.e., NP with a high pH could either have high or low nicotine concentration, or vice versa), and NPs were randomly assigned without replacement to ensure participants did not receive the same product more than once in each condition. Los Angeles metropolitan area in California, United States (U.S.). Seventy-three young adults (21-35 years, mean[standard deviation] = 23.7[3.1] years; 87.7% males, 49.3% White) who currently use NPs were recruited between October 2024 and July 2025. Participant rated ONP appeal and sensory attributes (sweetness, smoothness, bitterness, harshness) on 0 ('not at all') to 100 ('extremely') scales. Repeated-measures random-intercept models assessed the effects of nicotine concentration and pH on the appeal and sensory attributes. In the sample, high (vs. low) nicotine strength produced statistically significant lower ratings of appeal (b = -8.75, 95% confidence interval [CI] = -15.41, -2.08) and smoothness (b = -7.72, 95% CI = -14.01, -1.44) and higher harshness ratings (b = 7.21, 95% CI = 1.07, 13.36). No statistically significant linear effects of pH on appeal and sensory attributes were observed. Quadratic analyses revealed non-linear associations whereby ONP appeal and sweetness declined at both tails of the pH distribution (inverted U-shape). Statistically significant interactions between nicotine concentration and quadratic pH were observed for appeal and bitterness with stronger quadratic pH effects in high (vs. low) ONPs. In addition, statistically significant pH-sex interactions showed stronger quadratic effects in females (vs. males) for appeal and bitterness. In this double-blind randomized experiment among young adult oral nicotine pouch (NP) users in the United States, exposure to NPs with [1] higher vs. lower nicotine concentrations produced lower appeal and smoothness and greater harshness; [2] varying pH produced non-linear effects, such that appeal and palatability rose at moderate pH levels and then declined at high pH levels, particularly for high-nicotine NPs and among females.
On 9 June 2022, Thailand changed its cannabis legislation, expanding access to individuals aged >18 years. Evidence suggests that such changes could increase the risk of cannabis use and related harms, and could influence patterns of use of other substances among adolescents. This study measured the potential impact of these legislative changes on adolescent substance-related hospital admissions. An interrupted time-series study to assess the impact of cannabis legalisation on substance-related hospitalisations using anonymised admission records from the Thai Health Information Portal. Nationwide study in Thailand spanning from 1 October 2016 to 30 September 2023, with 9 June 2022 marking cannabis legalisation. Adolescents aged 10-19 years in Thailand. Based on International Classification of Diseases, 10th Revision diagnostic codes, hospitalisation records were classified as relevant or irrelevant to each of eight predefined substance categories: stimulants (excluding cocaine), alcohol, cannabis, sedatives (including opioids and narcotics), volatile solvents, nicotine, hallucinogens and cocaine. There were an additional 25.5 weekly cannabis-related hospitalisations (95% prediction interval = 23.5-27.2) compared with counterfactual predictions, resulting in 1762 excess cases over the 68-week post-legalisation period. Statistically significant excess admissions were also observed for stimulants, nicotine, volatile solvents and hallucinogens, corresponding to additional admissions of 9.1, 1.4, 0.5 and 0.5 per week, respectively (95% prediction intervals = 0.3-15.4, 0.4-2.1, 0.3-0.7 and 0.2-0.7, respectively). No statistically significant changes were observed for alcohol-, sedative- or cocaine-related hospitalisations. Cannabis legalisation in Thailand was followed by a marked rise in adolescent hospitalisations related to cannabis, alongside an increase in stimulant-, nicotine-, volatile solvent- and hallucinogen-related hospitalizations. These findings highlight the potential unintended consequences of cannabis legalisation in Thailand and underscore the need for preventive strategies to reduce adolescent exposure and related harm.
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NEET (Not in Employment, Education or Training) youth represent a vulnerable population from a public health perspective, facing multiple health challenges, including elevated substance use. Tobacco and cannabis are the most commonly used psychoactive substances among young people, with early initiation associated with long-term health and social consequences. While evidence suggests associations between NEET status and substance use, data remain limited regarding patterns of use and potential variations across different NEET profiles. This study aimed to characterise tobacco and cannabis use within the NEET population, taking into account the diversity of profiles, and to compare it with that of the general population, including employed youth and students, in order to inform targeted prevention strategies. A systematic review and meta-analysis included observational studies examining tobacco and cannabis use among NEET youth aged 15-29 years. A search was conducted for observational studies available on PubMed, PsycINFO, Cairn and Web of Science databases and published between 1999 and 2025. Analyses studied the variations in use among NEET profiles and compared NEET against employed youth, student and general population controls. Random-effects models generated pooled crude odds ratios. Sensitivity and subgroup analyses were conducted based on study quality, gender and type of comparison population. Twenty-five studies were included and analysed, including a total of 91 085 individuals. A statistically significant association between NEET status and both tobacco use [odds ratio (OR) = 1.92, 95% confidence interval (CI) = 1.46-2.53] and current cannabis use (OR = 2.14, 95% CI = 1.68-2.71) was found. Current smoking was statistically significantly more prevalent among NEET than among students (OR = 3.05, 95% CI = 2.31-4.03), but not statistically significantly different compared with young workers (OR = 1.10, 95% CI = 0.91-1.34). NEET demonstrated statistically significantly higher cannabis use compared with both students (OR = 1.81, 95% CI = 1.34-2.44) and workers (OR = 1.67, 95% CI = 1.21-2.31). A higher prevalence of cannabis use disorder among young people with NEET status (31.93%) was observed compared with their non-NEET peers (12.12%), but no statistically significant association was found. Youth Not in Employment, Education or Training (NEET) appear to show higher tobacco and cannabis use compared with their peers. Given these findings, targeted prevention strategies addressing substance use in NEET populations are essential to reduce social health inequities.
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Memory loss from alcohol use ('blackout') is a prevalent and costly indicator of substance-related harm. While alcohol-induced blackouts can be assessed retrospectively via self-report, no tool exists to identify blackouts objectively in real time, hindering progress in research as well as intervention efforts. This study tested the feasibility and diagnostic accuracy of real-time memory tasks in identifying alcohol-induced blackouts in situ. Prospective diagnostic study. United States. Young adults (18-30 years of age; n = 63) reporting recurrent memory loss as a result of alcohol use were recruited from across the United States between December 2022 and January 2024. Participants completed a baseline survey and orientation interview, followed by 30 days of ecological momentary assessments (EMA). EMA included recall and recognition tests for visual stimuli during drinking events (index tests) and subsequent self-reports of blackout (reference standard). At the end of the protocol, participants also completed a Timeline Followback interview of blackout events during the assessment period. Primary outcomes, which were specified prior to data collection, were (a) feasibility of memory task completion during drinking events and (b) diagnostic accuracy of memory tasks in identifying blackout at the event level. Data were analyzed using Bayesian logistic multilevel models. Of the 63 participants included [mean age = 23.2, standard deviation (SD) = 3.3; 78% female, 51% White], 38 (60%) self-reported a blackout during the assessment protocol. On average, participants completed 85% of memory tests prompted (SD = 16.42). Within days, both greater-than-average number of drinks [odds ratio (OR) = 1.74; 95% confidence interval (CI) = 1.41-2.19] and failure of 1 + recall memory test (OR = 15.53; 95% CI = 5.96-36.27) were associated with increased odds of blackout. In model-predicted probabilities, blackout probability was ~0.01 if a person consumed their average number of drinks, ~0.21 if they had five more drinks than average and ~0.34 if they failed 1 + recall test. Participants self-reported blackout on 39% of the days that they failed 1 + recall memory test (positive predictive value; 95% CI = 30-49); however, they reported not having a blackout on 92% of days that they correctly recalled all memory tests (negative predictive value; 95% CI = 89-95). Objective measures of alcohol-induced blackout can be implemented in real-life contexts. Failing a visual memory test while intoxicated is not necessarily indicative of blackout; however, correct recall indicates that blackout is highly unlikely.