The immune system and inflammation have emerged as critical components in alcohol use disorder (AUD). The inflammatory molecule lipocalin-2 (LCN2) has been investigated in alcohol-associated liver disease, and assessment of LCN2 concentrations may aid in prevention and treatment of AUD. However, it is unknown how LCN2 concentrations fluctuate in response to acute and chronic alcohol exposure. We examined plasma LCN2 concentrations in rats made alcohol-dependent via chronic, intermittent alcohol vapor exposure, and in people with AUD after acute alcohol administration. We hypothesized that chronic and/or acute alcohol exposure would alter LCN2 concentrations. Plasma LCN2 concentrations were measured in alcohol-dependent ( = 9) and nondependent ( = 8) male rats. LCN2 concentrations were also examined in two human laboratory studies with cue-reactivity and oral/intravenous alcohol administration in 15 (80% males) and 16 (68.8% males) participants with AUD, respectively. A significant effect of Timepoint (morning versus afternoon;  = .001) but not of chronic alcohol exposure on LCN2 concentrations were found in rats. No significant effects were found after acute alcohol administration in humans. Chronic alcohol exposure in rats or acute alcohol administration in people with AUD had no impact on LCN2 concentrations. In rats, LCN2 concentrations were lower in the morning than in the afternoon, indicating time-related variations in LCN2 concentrations. Together, these findings suggest that LCN2 might play a role in the circadian rhythm, which is often disrupted in people with AUD. However, prospective studies are needed to further examine LCN2's potential clinical relevance in AUD.Clinical Trials Numbers: NCT01751386, NCT01779024.

Substance use disorders are more prevalent in areas of extreme poverty. Few studies have evaluated the differences in quality of addiction treatment associated with persistent poverty status (counties where at least 20% of residents have been in poverty for 20 years or more) and Medicaid access. This study aims to (1) investigate whether there is a difference in the quality of addiction treatment between counties identified as persistent poverty counties and those not and (2) determine the effect of Medicaid expansion on quality. We analyzed data from the National Substance Use and Mental Health Services Survey and the US Census American Community Survey. We performed fixed and random effects regression analysis to determine the likelihood of access to high-quality care, including evidence-based behavioral health services, medications for addiction, staff accreditation, medical treatment, recovery services, increased access to treatment, personalized-treatment plans, and long-term services. Adjusted regression results revealed that persistent poverty county status was associated with a higher likelihood of access to high-quality care in states that expanded Medicaid (OR = 1.37, 95% CI 1.10, 1.70). Persistent poverty counties were also more likely to provide medical services, rapid access to treatment, and personalized treatment plans. However, only access to medical services remained significant in the unadjusted model in states that did not expand Medicaid (OR = 2.10, 95% CI 1.03, 4.30). Substance treatment providers in persistent poverty counties were more likely to provide higher quality care, but Medicaid expansion played an important role. Implications for substance treatment policy and practitioners are discussed.

The Alcohol Use Disorders Identification Test (AUDIT) is a widely used screening tool for assessing problematic alcohol use. While strong cross-sectional psychometric support exists, little is known about its longitudinal performance, particularly within Australian populations and over extended intervals. Most prior studies have relied on short test - retest periods (2-6 weeks), simple correlations, and have not examined whether the AUDIT consistently measures the same constructs over time. This study addresses these gaps by using longitudinal confirmatory factor analysis (CFA) to examine the AUDIT's factorial structure, test - retest reliability, and measurement invariance over a 12-month period. A sample of 276 Australian adults (mean age = 31.86 years; SD = 9.94; 71% male), all current alcohol consumers, completed the AUDIT at two time points (2022 and 2023). Participants reported regular alcohol use, with an average AUDIT score of 7.14 at T1 and 7.78 at T2; 38.9% exceeded the threshold for hazardous drinking. One-, two-, and three-factor models were compared, with the one-factor model showing the best fit (RMSEA = .078). The AUDIT demonstrated moderate test - retest reliability ( = .67) and partial longitudinal measurement invariance. Only a small number of factor loadings and intercepts were non-invariant. Full support was found for latent variance invariance, latent mean equivalence, and structural invariance. These findings offer novel longitudinal evidence for the psychometric stability of the AUDIT over 12 months in an Australian sample, supporting its value for monitoring alcohol use and evaluating treatment outcomes.

Prescription opioid misuse (POM) remains a significant public health concern among college students, yet few studies have examined POM prevalence, misuse behaviors among those with prescriptions, and how students access opioids in college settings. Assessing the prevalence of POM, patterns of opioid sourcing (i.e. prescribed vs. illicit), and the trends of misuse of one's own prescription (i.e. higher dosage and/or frequency) among college students. Data from the 2019-2022 American College Health Association-National College Health Assessment III survey, including responses from 331,156 students (64.4% cisgender female), were analyzed. Descriptive analyses assessed POM prevalence and misuse patterns, while multivariable logistic regression identified factors linked to illicit opioid sourcing and prescribed opioid misuse (higher dosage and/or increased frequency). Lifetime POM was reported among 3.9% ( = 12,983) of students and past three-month POM was reported among 0.7% of all students ( = 2,327). Of participants with recent misuse, 55.5% used opioids that were not prescribed to them, and 44.5% used their own prescriptions. Among those with prescriptions, 26.0% exceeded the recommended dosage, and 22.7% shortened the dosing interval. Illicit sourcing was more common among gender-diverse students (aOR: 2.72, 95% CI: 1.62-4.71,  < .0001) and those with severe psychological distress (aOR: 1.42, 95% CI: 1.11-1.82,  = .0053). Misuse of higher dosages (aOR: 2.92, 95% CI: 2.07-4.32,  < .0001) and increased use frequency (aOR: 1.79, 95% CI: 1.23-2.63,  = .0026) was linked to suicidal risk. Prescription monitoring, substance use education, and harm reduction strategies to mitigate misuse risks are needed.

Timely initiation and continuation of medications for opioid use disorder (MOUD) following a new opioid use disorder (OUD) diagnosis reduces overdose risk. To examine patient- and community-level factors associated with timely MOUD receipt and the association of these factors and MOUD modality (buprenorphine, methadone, naltrexone) with subsequent overdose. This cohort study included Medicaid enrollees in 44 states aged 18-64 with a new OUD diagnosis between April 2016 and December 2019. Multivariable Cox Proportional Hazards models assessed time (in days) to MOUD receipt and medically-treated nonfatal overdose stratified by involvement of heroin/synthetic vs. other (primarily prescription) opioids only. Models adjusted for patient, county, and state-level covariates, and models examining overdose additionally adjusted for time-varying (daily) MOUD receipt. Of 1,172,200 Medicaid enrollees with a new OUD diagnosis, 51.8% were female, 55.8% White, and 42.2% aged 30-44. Most (69.2%) did not receive MOUD within 180 days. MOUD receipt was lower among Black (Hazard Ratio [HR] = 0.68, 95% Confidence Interval [CI] 0.67-0.69) and Hispanic (HR = 0.91, 95%CI = 0.90-0.92) compared to White enrollees. During follow-up, 3.2% of enrollees experienced heroin/synthetic opioid overdose, with reduced risk more strongly associated with methadone (HR = 0.14, 95%CI = 0.12-0.15) and buprenorphine (HR = 0.23, 95%CI = 0.22-0.25) than naltrexone (HR = 0.70, 95%CI 0.64-0.77). Use of methadone and buprenorphine, and to a lesser extent naltrexone, are associated with lower overdose risk among Medicaid beneficiaries newly diagnosed with OUD. State and local policies aimed at increasing timely, equitable, and sustained treatment receipt are needed to address the opioid epidemic and reduce disparities.

Although religious and cultural factors have been related to substance use in various populations, research is needed regarding associations for Arab Americans. We examined how ethnic identity and religiosity relate to the odds and frequency of alcohol and cannabis use in Arab American college students during the COVID-19 pandemic, as well as differences by biological sex and Muslim upbringingArab American college students ( = 173; M = 20.1, range 17-23; 60.7% female; 44.5% Christian upbringing, 43.9% Muslim upbringing) were recruited through electronic flyers and a psychology subject pool in California. Participants reported their ethnic identity affirmation (i.e. feeling positively about being Arab American) and search (i.e. learning about Arab culture), religiosity, and past-year alcohol and cannabis use Greater ethnic identity affirmation was related to less frequent alcohol (OR = .68,  = .046) and cannabis use over the past year (OR = .58,  = .030), whereas greater ethnic identity search was related to lower odds of alcohol (OR = 0.66,  = .025) and cannabis use (OR = 0.68,  = .025). Greater ethnic identity search was also related to less frequent alcohol use among individuals from Muslim upbringings (OR = .37,  = .004). Greater religiosity was related to less frequent alcohol (OR = .61,  = .015) and cannabis use (OR = .44,  = .005). It was also related to lower odds of using alcohol and cannabis, with significantly stronger associations among individuals from Muslim upbringings (OR = .39,  = .040; OR = .40,  = .048) Ethnic identity and religiosity buffered substance use risk. Culturally tailored interventions and supporting cultural experiences may reduce Arab American students' substance use.

Despite the availability of efficacious opioid use disorder (OUD) medications (MOUD), there are racial and ethnic disparities in their use in the general population. Here, we examine the use of MOUD in a racially and ethnically diverse veteran sample. To examine racial and ethnic differences in veterans' 1) likelihood of receiving MOUD and 2) treatment retention, dosage, and abstinence outcomes among veterans receiving buprenorphine treatment. Among 29,502 veterans with OUD, we examined the effects of race and ethnicity on 1) whether methadone or buprenorphine was prescribed as MOUD, and 2) among those prescribed buprenorphine, using multivariable logistic regression to adjust for potential confounders, the likelihood of receiving ≥180 days of treatment and achieving opioid abstinence. Thirty percent of veterans with OUD received MOUD, with race being a significant predictor ( < .01): White veterans were most likely to receive buprenorphine (12%) or both medications (11%), while Black veterans were most likely to receive only methadone (16%). Among 5,768 veterans prescribed buprenorphine, retention was highest among American Indian/Alaska Native (59%), White (59%), and Other race (62%) veterans and lowest among multiracial (47%) and Black veterans (49%). In an adjusted analysis ( = 3,273, 92% male, 8% female), Black veterans had significantly lower odds of opioid abstinence than White veterans (aOR = 0.53, 95% CI = 0.43, 0.67). There are racial disparities in MOUD prescribing and rates of retention, particularly in the rate of abstinence among buprenorphine-treated veterans. Standardized criteria for MOUD selection may help guide clinical decisions and reduce racial disparities in treatment outcomes.

Understanding which subgroups of vocational education students are more likely to use tobacco and/or alcohol is critical for designing interventions. Previous research has not explored important student subgroups. This exploratory study examined tobacco use, risky alcohol consumption not meeting Australian guidelines, and concurrent use by type of vocational training and whether previously unexplored factors were associated with these health behaviors among vocational education students. A cross-sectional online survey was conducted among 1057 students (66% male) attending 14 Technical and Further Education campuses in New South Wales, Australia. Type of vocational training was not associated with tobacco use, risky alcohol consumption, or concurrent use. Participants who were married/living with a partner (adjusted odds ratio (AOR): 0.69; 95% Confidence Interval (CI) 0.48, 0.99), or unemployed (AOR: 0.60; 95% CI 0.36, 0.99) had significantly lower odds of tobacco use. Indigenous students (AOR: 1.82; 95% CI 1.19, 2.80) or those who experienced symptoms of depression (AOR: 1.69; 95% CI 1.12, 2.55) had significantly higher odds of tobacco use. Participants aged ≥25 years (AOR: 0.59; 95% CI 0.40, 0.88), female (AOR: 0.42; 95% CI 0.29, 0.62), or unemployed (AOR: 0.57; 95% CI 0.37, 0.88) had significantly lower odds of risky alcohol consumption. Unemployed participants (AOR: 0.53; 95% CI 0.30, 0.95) had significantly lower odds of concurrent use. Those who experienced symptoms of anxiety (AOR: 1.55; 95% CI 1.02, 2.37) had significantly higher odds of concurrent use. Vocational education institutes could provide tailored and culturally appropriate interventions targeting students at increased risk of tobacco and/or alcohol use to prevent diseases.

People with opioid use disorder (OUD) experienced worse outcomes from the COVID-19 pandemic, which disrupted general medical care. To quantify COVID-19 impact on OUD treatment disengagement among patients in office-based addiction treatment (OBAT) with buprenorphine. We recruited 112 outpatients actively on buprenorphine at enrollment from July 2021 to 2022 for telephone surveys within a prospective cohort study. Exposures were six COVID-19 impact domains: personal or family COVID-19 infection, difficulty accessing healthcare/medications, economic stressors, worsening physical or mental health, social isolation, and conflicts and disruptions in the home. The primary outcome was time to OBAT disengagement. We examined associations between each COVID-19 impact domain score and the composite COVID-19 pandemic impact score (a sum of all scores) with time to disengagement using Cox regression models. Average age was 48 years, 56.3% male, 71.2% white/non-Hispanic, 67% Medicaid insurance and 92.9% housed. The majority (74/112) had started in OBAT prior to the pandemic. Median time to disengagement was 271 days. Neither unadjusted nor adjusted analyses showed significant associations between COVID-19 impact domains and time to disengagement. The adjusted hazard ratio for composite COVID-19 impact score was 1.00 (95% CI: 0.99, 1.02). Negative COVID-19 impacts were prevalent among patients in OBAT, but none were significantly associated with time-to-care disengagement. Most patients had multiple protective factors (male, white/non-Hispanic, housed, and Medicaid insurance) and this OBAT rapidly adopted telemedicine, which may have minimized treatment disruption. Preserving patient insurance access and telehealth may maximize OUD treatment retention despite pandemic stressors.

Healthcare readmissions are often perceived as negative outcomes. However, in the context of substance use disorder (SUD) treatment, they may reflect both systemic gaps and sustained engagement. Despite their frequency, the determinants of SUD readmission remain underexplored, particularly in Latin America, where non-injected drug use is highly prevalent. To identify factors associated with SUD treatment readmission and examine contextual influences shaping readmission risk in Chile. We employed a mixed-methods parallel convergent design. Quantitative analyses included 107,559 treatment episodes (84,978 males; 22581 females) recorded from 2010 to 2019. We estimated Average Hazard Ratios (AHR) using a PWP-GT model. Qualitative data from 14 in-depth interviews explored social, familial, and environmental contributors to readmission. Compared to those who did not complete, completing ambulatory treatment was associated with a lower risk of readmission (AHR = 0.83, 95% CI: 0.78-0.88), while no significant effect was found in residential programs. Women had a higher risk of readmission than men in both ambulatory (AHR = 1.36, 95% CI: 1.31-1.42) and residential settings (AHR = 1.42, 95% CI: 1.33-1.51). Qualitative findings revealed reintegration difficulties post-discharge, especially in high-risk environments. Gender roles pressured women to seek treatment, particularly when they were primary caregivers. Support for caregiving responsibilities may enhance treatment retention and reduce readmissions among women. Clinicians and policymakers should consider implementing structured post-discharge follow-up and community-based support systems, especially after residential treatment, to mitigate environmental risks and sustain recovery.

American Indian communities consistently identify adolescent substance use as a major concern. However, limited empirical work has examined how culturally specific protective factors - such as family disapproval and cultural affiliation - interact to influence substance use behavior. Given the importance of kinship networks and cultural continuity, understanding these dynamics is critical for informing culturally grounded prevention strategies. This study examines the moderating role of cultural affiliation in the association between family disapproval of substance use and actual use among American Indian adolescents, a population often excluded from national health datasets. Secondary analysis was conducted using self-report data from the study, a nationally representative sample of American Indian adolescents attending schools on or near reservations ( = 8,950; 51% female; Mage = 14.64 years, SD = 1.77). Multilevel analyses revealed that family disapproval was negatively associated with lifetime alcohol (b = -0.15,  < .001) and cannabis use (b = -0.34,  < .001), controlling for age. Among adolescents who endorsed use, cultural affiliation moderated the relationship between family disapproval and past-year alcohol and cannabis use. Specifically, family disapproval was significantly associated with lower alcohol use at high (b = -0.01,  = .002) but not low (b = -0.07,  = .48) levels of cultural affiliation. For cannabis use, the association was stronger at high (b = -0.51,  < .001) versus low (b = -0.32,  = .005) levels. Cultural affiliation strengthens the protective effects of family disapproval on substance use among American Indian youth. Findings support culturally responsive, family-based prevention efforts that promote cultural identity and intergenerational communication.

Drug checking is a harm reduction intervention that uses chemical analytical methods to provide information on the composition of illicit drug mixtures. It is necessary to expand the reach of drug checks to fully meet the needs of populations who use drugs who are at risk of overdose. Technical barriers to drug checking, such as software that is challenging to use without extensive training and practice, hinder the expansion of these services. This study describes the development, architecture, and deployment of a custom FTIR-based software framework. Components of this framework are useful across several models of drug checking. A kiosk application controls a spectrometer and uploads the spectral and survey data to a centralized database. An analysis suite facilitates spectral interpretation using libraries, a repository of previous data, and analysis tools. Individual drug checking results are accessible online. Aggregated data are viewed internally via a dashboard. Public-facing reports are tailored to different communities. The software was successfully deployed with a total of 6 remote service sites operating by 2024. Between May 2022 and December 2024, 2673 drug samples were checked for 1926 clients, including hundreds accessing drug checking for the first time. Weekly and monthly reports of aggregate drug data were created. By lowering technical barriers and supporting real-time reporting, our software framework expanded service access and provided actionable data to both communities and public health stakeholders. This method represents a meaningful advancement in the technological infrastructure necessary to sustain and expand drug checking efforts.

Alcohol use disorder (AUD) remains a major global health challenge with limited effective treatments. Ketamine, an NMDA receptor antagonist with rapid anti-craving and neuroplastic effects, has emerged as a promising novel therapy for AUD. To review the literature examining the safety and efficacy of ketamine for treating AUD. PubMed and Embase were searched to identify eligible studies published until December 2024. Studies were screened as per the eligibility criteria. Appropriate Joanna Briggs Institute tool was used for risk of bias assessment. A narrative synthesis of findings from the included studies was done. The review protocol was pre-registered in PROSPERO (CRD42022318120). Six studies comprising a total of 605 patients (528 male) from three different countries (USA, UK, Russia) were reviewed. Five of them reported favorable effects of adjunctive ketamine treatment on a range of different alcohol-related outcomes such as abstinence rates or period, alcohol-related craving, and number of heavy drinking days. However, methodological differences including variations in ketamine dosing strategies (route: oral, IV, IM; dose/session: 0.5 mg/kg IV to 2.5 mg/kg IM; number of sessions: 1-3), treatment duration, sample characteristics, and method used for measuring study outcomes led to significant heterogeneity and limited comparability of results. No study reported any serious adverse event or ketamine misuse following ketamine treatment. This review underscored ketamine's potential as an adjunctive treatment for AUD. While promising, considerable variability in dosing, therapeutic approaches, and study designs limits the certainty of evidence. Future research examining the long-term safety and efficacy of ketamine is needed.

Perceived Substance Use Disorder (SUD) stigma, defined as the awareness of negative societal attitudes toward individuals with SUDs, may discourage treatment-seeking and completion. Unlike self-stigma (negative beliefs about oneself), perceived stigma reflects individuals' perceptions of stigma from the public. While self-stigma has been widely studied, research on perceived stigma's role in shaping treatment outcomes remains limited. This study aimed to examine whether higher perceived stigma at treatment intake predicts premature treatment discontinuation and hypothesized that greater perceived stigma would be associated with increased rates of premature treatment discontinuation. A total of 7,591 participants (70.2% male) from 75 SUD treatment facilities across the United States completed surveys at treatment intake and early in treatment. Perceived stigma was assessed using the Perceived Stigma of Addiction Scale (PSAS). Treatment completion, defined as standard discharge (recommended duration of care), served as the primary outcome. Mixed-effects models evaluated the relationship between perceived stigma and treatment discontinuation while adjusting for demographic, SUD, and mental health-related covariates. Higher perceived stigma significantly predicted an increased likelihood of premature discontinuation (adjusted odds ratio [AOR] = 0.97, 95% CI [0.95, 0.99],  < .001). For each one-unit increase in PSAS score, the odds of treatment completion decreased by 3%. This relationship persisted across all models, even after accounting for covariates. These findings underscore the importance of addressing perceived stigma at treatment intake and its role in predicting treatment retention. Routine screening for stigma and implementing stigma-reduction interventions during care may contribute to better treatment outcomes for individuals with SUDs.

Opioid use disorder (OUD) is a chronic relapsing condition with a high mortality rate. While medications such as methadone are valuable first-line therapies, retention is poor, with the highest dropout rates early in a treatment attempt. Poor outcomes are due in part to the very high rates of co-morbid depression in people with OUD, as depression can drive opioid use. Therefore, administering a rapid-acting antidepressant such as ketamine early in a treatment attempt may be an effective strategy to improve outcomes. Here, we describe a case series of three patients (two males, one female) diagnosed with OUD initiating methadone treatment and endorsing symptoms of depression, who met criteria for a single-arm open-label feasibility trial (NCT05051449) at an opioid treatment program in Baltimore, Maryland. Participants underwent a 2-week ketamine regimen (0.5 mg/kg infusion over 40 min, three times per week for 2 weeks). Ketamine was safe and generally well-tolerated. At 10-day follow-up post-ketamine infusions, participant acceptability ratings were mostly favorable. All three patients remained in treatment through the 3-month timepoint with strong treatment adherence. With treatment, self-reported depression symptoms decreased from severe to mild/moderate in two patients, and from moderate to remission in the third. Randomized controlled trials are warranted to test whether ketamine may be a feasible and safe adjunctive treatment for OUD in patients initiating methadone treatment.

Exposure to (RED) is positively associated with alcohol-related outcomes among Hispanics; however, links between RED and alcohol use are poorly understood, particularly when considering RED in social media. Study aimed to (1) examine the direct and indirect associations between RED on social media and alcohol use severity (i.e., AUDIT total score) via coping drinking motives (a form of negative reinforcement in which an individual uses alcohol to alleviate/regulate negative emotions) among Hispanic emerging adult college students, and (2) examine if psychological resilience moderates the direct and indirect associations of social media discrimination on alcohol use severity. A convenience sample of 423 (women = 300, men = 123) Hispanic college students from Texas and Florida completed a cross-sectional online survey. Data were analyzed by conducting a conditional process analysis. Social media discrimination did not have a direct association with alcohol use severity (β = .05, 95% CI=[-.03, .13], > .05), but it did have a statistically significant indirect association with alcohol use severity via coping drinking motives (β = .08, 95% CI = [.03, .13], < .05). Further, psychological resilience functioned as a moderator that weakened the indirect association between social media discrimination and alcohol use severity (β = -.14, 95% CI=[-.23, -.05], < .001). Our conditional process analysis may help guide etiological studies on RED and alcohol use. The data suggest that psychological resilience and coping drinking motives may be relevant constructs for interventions that aim to mitigate the association between RED and alcohol use.

People with opioid use and opioid use-related problems are highly stigmatized groups. Negative attitudes and perceptions held by healthcare providers and the stigma that results are key barriers to treatment entry and treatment provision. A contemporary measure for assessing the attitudes and perceptions of healthcare providers toward this population is needed. The current study aims to examine the psychometric properties of an adapted person-centered opioid and opioid problems perception questionnaire (PC-OOPPQ). The adapted PC-OOPPQ psychometric properties were assessed using a nationwide online sample of practicing nurses ( = 493, 460 were female nurses). The sample was randomly divided to perform exploratory (EFA;  = 247) and confirmatory (CFA;  = 246) factor analyses. Using the principal axis factoring (PAF) with orthogonal (Varimax) rotation, the EFA indicated a 19-item four-factor structure (without item # 16), which explained 70.2% of the total variance. Meanwhile, the CFA recommended an 18-item five-factor structure (without items # 14 and 16) that had the best model fit (Comparative Fit Index (CFI) = .938, the Tucker-Lewis Index (TLI) = .924, Standardized Root Mean Square Residual (SRMR) = .055, and Root Mean Square Approximation (RMSEA) = .088)). Apart from one item (item # 16), the proposed five-factor structure is consistent with the person-centered drug and drug problems perception questionnaire factor structure. The current study aims to address stigma associated with opioid use among healthcare professionals using language.

The minimum legal age (MLA) for non-medical cannabis use remains a contentious issue. While current regulations range from 18 to 21 years across jurisdictions, some advocates propose raising the threshold to 25, arguing that brain maturation continues until that age. They postulate that even individuals 22 through 25 exhibit increased neurodevelopmental vulnerability to cannabis. This Perspective examines this assertion, discussing the neuroscientific evidence on brain development and its implications for setting legal age limits for cannabis use. While most major macrostructural and microstructural brain development occurs early in life, processes such as synaptic pruning, gene expression, and prefrontal cortical changes persist through adolescence, with more subtle changes extending into the third decade. Nonetheless, there is no empirically defined neurodevelopmental endpoint at age 25. Brain maturation is a nonlinear process, region-specific, influenced by sex and specific physiological processes. Importantly, existing evidence does not demonstrate greater long-term cognitive or neurophysiological harm attributable to cannabis use in individuals aged 18-25 years compared to those older than 25. This Perspective concludes that an MLA between 18-21 years is a scientifically supportable and socially coherent threshold for non-medical cannabis use. Policy decisions should be informed not only by neurobiological evidence but also by legal, justice, sociocultural, psychological, and historical considerations.

Recent studies have quantified the rate of fatal overdoses that involve opioids, stimulants, and other drugs, but the proportion of overdose deaths attributable to these substances - after accounting for polysubstance use - has not been determined. We aim to generate the first estimates of the share of overdose deaths by substance type from 1999 to 2021. By analyzing the National Vital Statistics System's mortality files, we calculated the percent of overdose deaths ( = 1,043,852, 30% female) by substance type in the US for the years 1999 to 2021. We offer and rely on two novel methods: the single-substance method and the apportioned-substance method. In 2021, opioids accounted for 56% (apportioned-substance) to 64% (single-substance) of overdose deaths and stimulants accounted for 30% (single-substance) to 34% (apportioned-substance), which means that opioids and stimulants accounted for 89% to 94% of overdose deaths. From 1999 to 2021, fentanyl became an increasing share of opioid deaths (from 12%-14% to 78%-87%;  < .01) and methamphetamine became an increasing share of stimulant deaths (from 11%-12% to 60%-70%;  < .01). Opioid deaths and stimulant deaths comprised at least 89% of overdose deaths, and methamphetamine and fentanyl represented rising proportions of fatal overdoses. To prevent drug deaths, resources should be directed primarily to therapies and interventions for opioids and stimulants.

Adverse childhood experiences (ACEs) are linked to negative health outcomes. Yet how ACEs patterns are associated with non-fatal overdose among people who use drugs (PWUD) is underexplored, despite disproportionate rates of ACEs among this population. We examined latent classes of ACEs and their associations with non-fatal overdose in PWUD in New York City (NYC). We conducted a latent class analysis based on self-reported exposure to ACEs: emotional/physical neglect; emotional, physical, and sexual abuse; household mental illness; household substance use; domestic violence; parental separation/death; and household incarceration. Multivariable logistic regression assessed associations of ACEs classes with lifetime non-fatal overdose. Of 247 PWUD, 74.9% were men and 43.3% reported a lifetime non-fatal overdose. Identified classes were: 1) no/low ACEs (26.3%), 2) household dysfunction (parental separation/death, household substance use) (25.1%), 3) household dysfunction + emotional, physical, and sexual abuse (19.4%), 4) emotional and physical abuse (16.2%), and 5) experienced all ACEs (13.0%). Compared to no/low ACEs, those in the experienced all ACEs class (aOR 4.92; 95%CI 1.71-14.9) and in the household dysfunction class (aOR 3.14; 95%CI 1.31-7.77) had higher odds of experiencing a non-fatal overdose. Other factors associated with non-fatal overdose included unstable housing (aOR 2.73; 95%CI 1.40-5.42), moderate/high cocaine use disorder (aOR 2.60; 95%CI 1.05-6.71), and moderate/high opioid use disorder (aOR 4.25; 95%CI 2.07-9.14). Findings suggest that those who experience a broad spectrum of ACEs may be at higher risk of non-fatal overdose. Addressing early-life adversity in harm reduction and treatment interventions may help mitigate overdose risk in this population.