Background and aims: Appetitive responses, such as approach biases, are thought to play a crucial role in smoking. This study aimed to compare responses toward smoking-related stimuli with responses in control conditions (e.g. non-approach or neutral stimuli) using a multi-method approach. By examining associations between response measures and with smoking-related variables, the study sought to extend understanding of their role in abstinence-motivated, non-deprived individuals with chronic tobacco dependence.
Design and setting: Cross-sectional study conducted at a university laboratory and magnetic resonance imaging (MRI) scanner in Munich, Germany.
Participants: 362 chronically smoking individuals (51.38% female; data collection: November 2019-March 2023) with moderate-to-severe tobacco dependence, enrolled in a smoking cessation study, allowed ad libitum smoking prior to assessment.
Measurements: Responses toward smoking-related stimuli were assessed using cognitive-behavioral (reaction-time-based approach biases), psychophysiological (electromyography: corrugator supercilii, zygomaticus major and orbicularis oculi for acoustic startle reflex) and neural (functional MRI: regions relevant to smoking cue-reactivity) measures. Smoking-related variables were cigarettes per day, tobacco dependence severity and craving. Split-half reliabilities were estimated for all measures.
Findings: Participants exhibited a statistically significantly attenuated acoustic startle reflex toward smoking-related versus neutral stimuli (P < 0.001, Rosenthal's r = 0.39), while no statistically significant differences emerged for other psychophysiological or cognitive-behavioral measures. Neural measures showed statistically significantly heightened reactivity toward smoking-related versus neutral stimuli in sensory and motor regions (e.g. precuneus; P < 0.001, Rosenthal's r = 0.44) but reduced activity in reward-related regions (e.g. striatum; P = 0.021, Cohen's d = 0.22). Higher craving was statistically significantly associated with stronger appetitive responses on some measures from all assessment methods (Ps ≤ 0.041), whereas greater tobacco dependence and smoking behavior were linked to reduced neural reactivity toward smoking-related stimuli (Ps ≤ 0.036). No statistically significant associations emerged between measures from different methods (factor loadings ≤ 0.145, Ps ≥ 0.076). Differences scores between conditions (rel. = -0.351 to 0.837) were generally less reliable than their individual components (rel. = 0.619 to 0.964; excluding one exception) CONCLUSIONS: Appetitive responses toward smoking-related stimuli may play a limited role in abstinence-motivated, non-deprived individuals with chronic tobacco dependence, whereas habitual motor responses could be more crucial.
Aim: To conduct a pilot cluster randomised controlled trial (cRCT) of a gambling prevention intervention (PRoGRAM-A) among young people aged 13-15 to determine the utility of conducting a Phase III RCT assessing effectiveness and cost-effectiveness.
Design: Two-arm, pilot cluster randomised controlled trial with an embedded process evaluation, health economic scoping study and social network analysis. Six schools were identified based on Scottish Index of Multiple Deprivation and school roll size. Schools were randomised to either intervention (n = 4) or control (n = 2). The trial was delivered between October 2023 and November 2024.
Setting: Six state funded secondary schools in Scotland (four intervention, two control).
Participants: Students (intervention n = 762, and control n = 352) in secondary school year 3 (aged 13-15 years old).
Intervention and comparator: PRoGRAM-A (Preventing Gambling Related Harm in Adolescents), a peer-led social network intervention to protect young people, their friends and family members from gambling related harm (GRH). Control schools delivered their standard Personal, Social, Health and Education (PSHE) curriculum, which did not include any form of gambling education.
Measurements: The primary outcome of this study was whether progression to a full-scale Phase III cRCT was warranted, using pre-set progression criteria. These criteria sought to address uncertainties in the intervention and cRCT design with thresholds set according to a traffic light system.
Findings: All five progression criteria were met. All schools were recruited and retained in the study with minimal missing outcome data. The process evaluation indicated that PRoGRAM-A was acceptable to multiple stakeholders and delivered with fidelity to the delivery manual. The proposed primary outcome for a future Phase III cRCT was self-reported gambling participation (measured by asking about types of gambling participation 'in the last 4 weeks' and 'in the last 12 months'). This pilot study found no statictically significant differences between the control and intervention groups at follow-up.
Conclusions: The school-based gambling prevention intervention PRoGRAM-A appears to be an acceptable intervention which can be delivered with high fidelity. The trial methods were acceptable with all settings recruited and retained. Progression to a larger randomised controlled trial to test effectiveness and costs effectiveness is warranted.
Background and aims: Substance use disorder (SUD) is a polygenic psychiatric condition characterized by persistent drug use despite negative consequences. Several studies support that higher cognitive performance and educational attainment (EA) are associated with a reduced risk for SUD. Here, we aimed to understand better the genetic relationship between EA and SUD, using a general addiction risk-factor (addiction) as a proxy of SUD.
Method: We used GWAS summary statistics on EA (n = 766 345) and addiction (n = 647 703) and applied a multistep approach to: (i) examinate the genetic overlap between EA and addiction; (ii) test the polygenic contribution of addiction and EA on SUD diagnosis and its clinical heterogeneity in an independent in-house clinical sample (1427 individuals with SUD and 2309 controls); and (iii) dissect the genetic liability of addiction according to its role in EA and assessing its genetic overlap with SUD-related traits, other mental disorders and behavioral traits.
Results: We confirmed a negative genetic correlation between addiction and EA [rg = -0.33, standard error (SE) = 0.02, P = 1.14e-57]. When we dissected the genetic liability of addiction by its relationship with EA we found that the discordant overlapping variation between addiction and EA, highly enriched for the genetic background of addiction (h2 SNP = 2.42%, P = 6.37e-21), showed the strongest effect on SUD (OR = 1.66, 95% confidence interval = 1.54-1.79, P = 2.01e-40) and was associated with worse sociodemographic, health and SUD-related outcomes in individuals with SUD compared with the other genomic partitions studied.
Conclusions: Our results provide new evidence on the shared genetic basis between addiction and educational attainment. By separating the genetic liability of addiction according to its relationship with educational attainment, we were able to clarify its polygenic effects on substance use disorder diagnosis and related outcomes, providing novel insights into the shared genetic signatures between addiction and other comorbid traits.
Conventionally used for its stimulant, empathogenic and entactogenic effects, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) is one of the most commonly used psychoactive drugs, specifically among young adults and in nightlife and recreational party contexts. Often perceived as a safe drug, MDMA can display an array of toxic effects on multiple organs, with hyponatraemia (a low blood sodium concentration that can cause an altered mental state) being increasingly reported. Although hyponatraemia per se is among the most common electrolyte disorders encountered in clinical care, acute MDMA-induced hyponatraemia was first described in 1993 and constitutes a life-threatening condition if left untreated, particularly among women, who present higher incidence rates and increased odds of developing severe clinical effects. The present review outlines the main clinical manifestations and prevalence of MDMA-induced hyponatraemia, its pathophysiological mechanisms and the therapeutical approaches to correct this electrolyte imbalance.
Background and aims: Despite multiple interventions, national-level trends of buprenorphine prescription use plateaued during a period of increasing opioid overdose deaths in the United States; county-level use trends may provide additional insights. We aimed to analyze county-level trends in buprenorphine treatment for opioid use disorder (OUD) and determine factors associated with trends.
Design: In this retrospective study, we used an iterative hierarchical cluster analysis to group counties with similar buprenorphine prescription use trends and then compared characteristics between clusters.
Setting: Retail pharmacy dispensing in the United States from 2018 to 2022.
Participants: Data on prescriptions dispensed for buprenorphine medications labeled to treat OUD.
Measurements: We analyzed standardized mean differences (SMD) and 95% confidence intervals (CI) of county-level characteristics between counties with varying trends in buprenorphine utilization.
Findings: Prescriptions dispensed for buprenorphine significantly increased in 924 counties (28% of US population) from 2018 to 2022 but declined in 839 counties (50%) from 2021 to 2022. Counties with decreasing (versus increasing) use had significantly higher opioid overdose death rates (SMD = -0.23; 95% CI = -0.34 to -0.13) and unemployment (SMD = -0.36; 95% CI = -0.46 to -0.27). Counties with increasing trends had higher percentages of residents in rural areas (SMD = 0.26; 95% CI = 0.16-0.35) and prescribing by nurse practitioners (SMD = 0.39; 95% CI = 0.29-0.48).
Conclusions: From 2018 to 2022, buprenorphine use as treatment for opioid use disorder increased in some United States counties, notably counties with more residents living in rural areas and counties with more prescriptions written by nurse practitioners. However, declining use in other US counties suggest challenges persist in increasing access to medication for treament of opioid use disorder, hindering progress in addressing the opioid crisis.
Aims: To examine age-specific trends in patterns of nicotine use in England between 2014 and 2024, including types of products used, exclusive and dual use of smoking and vaping, smoking frequency and the smoking history of those who vape.
Design: Repeat monthly cross-sectional analysis of data from a nationally representative survey (the Smoking Toolkit Study).
Setting: England, 2014-2024.
Participants: 217 433 adults (≥18y).
Measurements: Prevalence of (non-medicinal) nicotine use overall and by product type (combustible tobacco, e-cigarettes, heated tobacco products and nicotine pouches), exclusive and dual use of smoking and vaping, daily versus non-daily smoking and smoking history among those who vape. Estimates were stratified by age group (18-24, 25-34, 35-44, 45-54, 55-64, ≥65y) and year. Prevalence ratios (PR) with 95% confidence intervals (CI) were calculated to quantify relative changes in prevalence from 2014 to 2024.
Findings: Nicotine use patterns varied markedly by age. Among 18-24-year-olds, vaping prevalence increased fivefold, from 5.0% in 2014 to 25.0% in 2024 (PR = 5.00; 95% CI = 4.18-5.91), surpassing smoking by 2023. This contributed to an overall increase in nicotine use (26.1% to 36.5%; PR = 1.40; 95% CI = 1.29-1.53), despite declining smoking rates (25.3% to 19.9%; PR = 0.79; 95% CI = 0.71-0.88). In this age group, exclusive vaping became the most common mode of nicotine use, while nicotine pouch use also increased. Daily smoking declined substantially among 18-24-year-olds who smoked, with a shift toward non-daily smoking. Similar trends were observed among adults aged 25-44, though changes were smaller with increasing age. In older age groups (≥45), daily smoking declined modestly while vaping rose gradually, but there was little overall change in the prevalence of nicotine use. Most adults who vaped had a history of smoking, but the proportion who had never regularly smoked increased, particularly among 18-24-year-olds (4.3% to 34.3%; PR = 7.98; 95% CI = 4.56-26.2).
Conclusions: Generational shifts in nicotine use are occurring in England. Nicotine use has risen among young adults over the past decade, but they are increasingly moving away from daily cigarette smoking towards vaping or non-daily smoking. While older adults have also shown movement away from daily smoking, traditional smoking patterns remain more prevalent in this group. These trends suggest vaping may gradually replace smoking as the dominant form of nicotine consumption.
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