American Journal of Drug and Alcohol Abuse最新文献

Background: In utero cannabis exposure is associated with deleterious offspring neural development and behaviors that emerge across the lifespan. We explored if brain morphology differed in neonates exposed and unexposed to cannabis in utero in the first month of life.Objective: To evaluate differences in global and subcortical regional brain volume (in the amygdala and hippocampus) in neonates in the first month of life according to in utero cannabis exposure.Methods: Prospective pre-birth prospective cohort study of mother-infant pairs selected on the basis of prenatal cannabis use in the absence of alcohol, tobacco, or illegal drug use. The presence of cannabinoids using ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was quantified in maternal and neonatal biological samples. Neonatal MRI was conducted to evaluate differences in global and subcortical brain morphology between the exposed and unexposed infants (18 exposed, 21 unexposed). Inverse probability of treatment weighting was utilized in a generalized linear model framework to remove structural confounding bias between exposure groups. Clinical Trial Registration: NCT03718520.Results: The sex distribution of neonates was 43% female. Neonates exposed to cannabis in utero had significantly lower total brain volume (estimated effect size = 26,496.90 mm³, p = .02), independent of confounders including maternal stress, compared to unexposed infants. The unadjusted difference in brain volume was 29,159.82 mm³, p = .05). Regional volumetric differences were not detected in the amygdala or hippocampus.Conclusion: Given the evidence of the adverse effects of exogenous cannabinoids on fetal brain development, it is vital to prioritize prevention and cessation efforts targeting pregnant women.

Background: North America is experiencing an unrelenting overdose crisis driven by a volatile and toxic unregulated drug supply. Safer supply programs, which provide individuals with pharmaceutical-grade alternatives to the unregulated drug supply, have been implemented in various Canadian jurisdictions. While most programs provide tablet hydromorphone, the Safer Alternatives for Emergency Response (SAFER) program in Vancouver, Canada, offers pharmaceutical-grade fentanyl, including a powder formulation for witnessed consumption.Objectives: To explore early experiences among SAFER program participants receiving powder fentanyl.Methods: Qualitative one-on-one interviews were conducted with 18 (12 men, 6 women) people prescribed fentanyl powder from the SAFER program. Interview coding and analysis involved a team-based approach to identify common themes related to program experiences, focusing on impacts on unregulated drug use.Results: Most (13/18; 72%) participants reported reducing unregulated drug use since program enrollment. This was largely attributed to the SAFER fentanyl powder being effective for managing withdrawal, thereby limiting their need to access street-purchased drugs. Additionally, some participants, particularly those prescribed higher doses, suggested that SAFER fentanyl powder, unlike other safe supply medications, was a suitable alternative to street-purchased fentanyl. Participants also reported reduced overdose risk. Operating hours and dosing challenges were barriers to program engagement contributing to continued unregulated drug use for some.Conclusion: Our findings demonstrate a number of positive outcomes of the SAFER program and suggest that fentanyl safer supply has the potential to play a useful role in addressing the ongoing overdose crisis.

Background: Illegal opioids can create substantial harms, but the extent depends on multiple factors, including the amount consumed.Objectives: To examine how consumption varies across time and context, with implications for treatment and drug policy.Methods: We searched EBSCOhost and PubMed for literature on individuals: (1) not-in-treatment and purchasing from illegal markets, (2) reporting pre-treatment use at treatment intake, and (3) with opioid use disorder (OUD) receiving medically supplied opioids. A total of 135 articles were deemed relevant.Results: Average consumption intensities vary enormously, from below 100 morphine milligram equivalents (MME) per day for use outside of treatment where prices are high, to ~600 MME in typical illegal markets, and 1,100-1,800 MME per day when supply is free, as in heroin assisted treatment and injectable hydromorphone treatment. MME in methadone programs (190-460) is less than in the traditional British heroin prescribing system (600-1,300). Intensities tended to be higher in recent times, whereas the prices have been lower. Studies during the fentanyl era suggest MMEs per day may be much higher than in the past.Conclusion: The adaptability of consumption has several potential implications. Expansions in supply could have greater effects on quantity consumed than on prevalence. Treatment protocols and overdose prevention strategies may need to adjust for higher baseline consumption. Furthermore, assumptions about health harms from long-term use may need revisiting if they are predicated on lower, historical consumption intensities. These findings are caveated by limitations in reporting of data and variations in methodologies. Hence, greater investments in monitoring consumption intensities are warranted.

Background: Most state policies targeting pregnant people's alcohol use are ineffective, while some broader alcohol availability policies like government monopolies on retail spirits sales are effective. Previous research has not explored interactions of these policies.Objective: Analyze whether there are interactive effects between pregnancy-specific alcohol policies and government monopolies over retail spirits sales on infant and maternal outcomes.Methods: Outcome data were from Merative MarketScan®, a commercial insurance claims database, and included individuals who birthed singletons between 2006 and 2019 (N = 1,432,979 birthing person-infant pairs). We examined interactions between six pregnancy-specific policies and government monopolies. Regression models include (monopolyXpregnancy-specific policy) interaction terms, state and year fixed-effects, state-specific time trends, individual- and state-level controls, and clustering by state.Results: Associations of pregnancy-specific policies were generally stronger, or only present, in monopoly states. However, there was no consistent pattern regarding direction. Conversely, government monopolies consistently related to reduced infant maltreatment, with the largest effect when Priority Treatment for pregnant women policies were also in place [-1.64% (95% CI -1.87, -1.41)]. Protective associations of government monopolies on infant morbidities differed across reporting policies; for example, monopolies were protective without Reporting Requirements for child welfare [-0.28% (95% CI -0.40, -0.17)], but no longer protective with this policy [0.00% (95% CI -0.53, 0.55)].Conclusions: Government monopolies on retail spirits sales generally relate to reduced infant maltreatment and morbidities, although some pregnancy-specific alcohol policies blunt the protective effects of government monopolies. Repealing some ineffective pregnancy-specific policies - e.g. some Reporting Requirements - in monopoly states might improve infant outcomes.

Background: Major depressive disorder (MDD) and substance use disorders (SUDs) frequently co-occur, influenced by sex (biological) and gender (sociocultural) factors. The extent and consistency of these differences across substance types in populations with co-occurring MDD remains unclear.Objectives: This systematic review synthesizes evidence on sex and gender differences in the prevalence, clinical characteristics, and treatment outcomes of individuals with co-occurring MDD and four SUDs: alcohol use disorder (AUD), cannabis use disorder (CUD), opioid use disorder (OUD) and cocaine use disorders (CoUD).Methods: Following PRISMA guidelines, we searched PsycINFO, MEDLINE, and Embase for peer-reviewed studies from inception to present. Eligible studies examined co-occurring MDD and at least one SUD, and disaggregated outcomes by sex or gender.Results: Forty-seven studies were included (N = 648,414), spanning diverse age groups and geographic regions. Women with SUDs were more likely to experience co-occurring MDD, particularly in AUD and OUD; findings were less consistent for CUD and CoUD. Men with MDD were more likely than women to report co-occurring AUD. Co-occurring MDD-SUD conferred increased suicide risk, particularly among women. Treatment-related findings were mixed: some evidence suggested MDD increased relapse risk in men but buffered relapse in women. Common methodological limitations included inconsistent definitions of sex and gender and reliance on cross-sectional designs.Conclusion: Sex and gender shape the risks and treatment trajectories of co-occurring MDD and SUDs, underscoring the need for personalized screening, suicide prevention, and relapse management strategies. Greater conceptual clarity and inclusion of gender-diverse individuals could inform equitable clinical practices and targeted interventions.

Background: Substance-involved suicide and unintentional overdose deaths share risk factors, yet our understanding of how these deaths overlap and differ remains limited. Direct comparisons of substance-involved suicide and unintentional deaths are lacking.Objective: To guide effective prevention and intervention efforts regarding substance-involved suicide, we examined risk factors, demographic and substance-related, of substance-involved suicide and unintentional deaths.Methods: Using logistic and multinomial regression, we used medical examiner records obtained annually (N = 6,467, 72% male) to examine characteristics associated with suicide and unintentional substance-involved deaths in St. Louis, Missouri between 2011 and 2021.Results: Between 2011 and 2021, age-standardized suicide rates slightly decreased (3.55 to 3.33), while unintentional deaths nearly tripled (23.2 to 68.2). Many deaths involved both alcohol and traumatic injury, and almost a fifth of suicides involved prescription opioids. In the logistic model (combining data across 11 years), the following factors were associated with increased odds of suicide, relative to unintentional deaths: White race (OR = 5.42, 95%CI[3.95,7.56]), greater age (OR = 1.01, 95%CI[1.00,1.02]), traumatic injury (OR = 4.40, 95%CI[3.17,6.13]), and presence of not otherwise classified substances (including prescription medications; OR = 4.36, 95%CI[3.11,6.10]). The following were associated with decreased odds of suicide: presence of medical condition (OR = 0.32, 95%CI[0.23,0.45]), fentanyl (OR = 0.04, 95%CI[0.02,0.06]), ethanol (OR = 0.64, 95%CI[0.46,0.88]), cocaine (OR = 0.40, 95%CI[0.24,0.63]), heroin (OR = 0.05, 95%CI[0.03,0.09]), and other stimulants (OR = 0.32, 95%CI[0.20,0.50]).Conclusions: Results suggest a divergence over time in the rates of classified substance-involved suicide and unintentional deaths. A distinctive set of demographic and substance use characteristics differentiated the two manners of death, highlighting potential risk factors to inform further research and targeted interventions.

Background: Unplanned drinking episodes are empirically and conceptually linked with adverse outcomes, though recent research suggests planned drinking episodes may be riskier. Mixed findings may be due to unplanned drinking being operationalized as a dichotomous representation of the phenomenon (e.g. was drinking planned or unplanned) rather than continuous (e.g. the number of drinks beyond one's intended limit). Examining a continuous representation of the number of unplanned drinks consumed (i.e. consumed minus intended drinks) would permit a more nuanced evaluation of unplanned drinking and may be more predictive of consequences.Objectives: The present study aimed to describe the occurrence of unplanned drinking and disentangle the role of dichotomous vs. continuous operationalizations in predicting consequences.Methods: Participants were 104 (81.7% female; M_age = 20.75, SD = 1.99) undergraduate drinkers recruited through a psychology subject pool. Participants completed an online baseline survey followed by 14 brief, daily online surveys. Daily reports yielded an analytic sample of 325 drinking episodes.Results: Results indicated that most drinking episodes were planned but underestimated in quantity (i.e. consumption exceeded intentions). Only the continuous estimate of unplanned drinking was associated with negative consequences after controlling for dichotomous unplanned drinking (b = 0.25, IRR = 1.28).Conclusions: Results shed light on the need for a more nuanced operationalization of unplanned drinking behaviors, as current research utilizing a dichotomous lens may not be fully capturing the risky phenomenon. Results suggest that unplanned drinking, particularly related to consuming more drinks than intended, may be a useful indicator of problematic drinking.

Background: The opioid use disorder Cascade of care (OUD Cascade) is a public health framework used by federal/state/other agencies and researchers to facilitate monitoring and evaluating responses to the opioid epidemic, including surveillance and performance evaluation. As the use of the framework proliferates, there is an urgent need to standardize stage definitions to accurately monitor and improve patient outcomes and to align interpretation of findings across settings.Objectives: Define a taxonomy to uniformly apply the OUD Cascade to improve delivery of OUD services and better compare patient outcomes across settings and populations.Methods: We conducted a narrative review and synthesis focused on research and guidelines defining and measuring four key OUD Cascade stages: OUD identification, service engagement, medication initiation, and retention. Included articles come from peer-reviewed literature and define and/or operationalize OUD Cascade stages and associated measures across six characteristics based on an adaptation of the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist including: 1) settings, 2) specific population, 3) perspective, 4) time horizon, 5) assumptions, and 6) analytic method.Results: Our review (n = 27 articles) and synthesis provide an overview of how OUD Cascade definitions and framework designs have been variously applied. We found considerable heterogeneity in study approaches for all four OUD Cascade stages. We define a taxonomy to guide future research emphasizing standardized definitions to harmonize efforts across settings. In particular, we emphasize the need for clarity in defining criteria for sample construction (i.e. Identification), clear distinctions between receipt of care services generally (i.e. Engagement) from MOUD Initiation specifically, and Retention definitions that use a 30+ day gap in treatment to define discontinuation.Conclusion: Establishing a shared taxonomy for key terms specifying OUD Cascade stages will help the field advance, compare approaches and results across settings, and improve population-level patient outcomes.

Background: Alcohol-associated liver disease (ALD) results from excessive alcohol consumption, leading to liver damage such as steatosis and inflammation. Hypoxia and altered lipid metabolism contribute to ALD pathogenesis. HIF-1α, a key hypoxia regulator, and miR-185, a microRNA associated with ALD, are potential contributors to the disease.Objectives: To explore how HIF-1α and miR-185 regulate SR-BI and HDL metabolism in ethanol-exposed hepatocytes and their role in ALD-related lipid dysfunction.Methods: HL-7702 cells were treated with ethanol (25-200 mm) or hypoxia (1-2% O₂) for 24-72 hours to identify optimal conditions. miR-185 or HIF-1α inhibitors were used to assess SR-BI expression. Co-localization of HIF-1α and SR-BI was evaluated by immunofluorescence, and high-density lipoprotein cholesterol (HDL-C), which is critical in lipid metabolism, and triglyceride (TG) levels were measured by ELISA.Results: Ethanol exposure reduced cell viability in a dose- and time-dependent manner (200 mm for 72 h reduced viability by 43.7% ± 4.1%, p = .003). Exposure to 1% oxygen for 72 hours was confirmed as the optimal hypoxia model. Ethanol (200 mm) or hypoxia significantly increased HIF-1α (p = .002) and miR-185 expression (p = .001). These changes were accompanied by reduced SR-BI expression and elevated HDL-C and TG levels. miR-185 knockdown restored SR-BI expression (p = .003) and normalized HDL-C (p = .004) and TG levels (p = .005).Conclusions: Ethanol-induced HIF-1α and miR-185 upregulation disrupts HDL metabolism by suppressing SR-BI, impairing hepatic HDL uptake in ALD. Targeting this axis may offer new therapeutic strategies for ALD.