Comorbid substance use is common in patients with bipolar disorder (BD) and associated with a more severe illness course and higher mortality rates. We aimed to investigate 1) the prevalence of lifetime comorbid substance misuse in patients with newly diagnosed BD compared with healthy controls (HC), and 2) differences in illness characteristics between patients with and without comorbid substance misuse. We included 376 patients with newly diagnosed BD and 200 HC. Lifetime substance misuse (including alcohol and drug use) was identified through baseline interview and through systematic review of electronic health records. The prevalence of lifetime substance misuse was higher for patients with newly diagnosed BD (43%). Patients with BD had a high prevalence of lifetime comorbid drug misuse (38%) than alcohol misuse (19%). Among patients, lifetime substance misuse was associated with male sex (OR = 2.86 [1.82; 4.55] p < 0.001), childhood trauma (β = 5.33 [2.68; 7.99], p = 0.003), BD type I (OR = 1.71 [1.09; 2.68], p = 0.042), presence of suicide attempts (OR = 2.26 [1.36; 3.75], p = 0.005) and more sick days the preceding year (β = 41.43 [16.90; 65.96], p = 0.012). Information regarding substance use was partly gathered retrospectively using electronic health records. HC were recruited among blood donors and may not be representative of the general population. We found a high prevalence of lifetime comorbid substance misuse, particularly drug misuse in patients with newly diagnosed BD. Lower clinical focus on drug use than alcohol may have contributed to higher observed prevalence of drug use. This highlights the need for early clinical assessment and integrated treatment.
The present study aimed to characterize the prevalence and correlates of legal and illicit substance use, misuse (use of prescription medication other than prescribed), and hazardous use, including alcohol, cannabis, prescription drugs, and illicit drugs, among adults residing in communities that had experienced a mass violence incident (MVI). Using a household probability sample of adults (N = 5,991; 53.5% female; 70.6% White) from six MVI-affected communities, respondents completed surveys assessing sociodemographic characteristics, MVI-related experiences (i.e., degree of exposure), psychological risk factors (e.g., social support), probable mental health diagnoses, legal and illicit substance use, substance misuse, and hazardous use. Weighted prevalence estimates indicated that approximately one in five MVI-affected residents reported past-month binge drinking, with nearly one in ten reporting heavy alcohol use. Illicit substance use, substance misuse, and hazardous use were also prevalent. Several factors were consistently associated with increased odds of substance use outcomes, including high MVI exposure (OR = 2.01, 95% CI [1.30-3.10]), low social support (OR = 1.30, 95% CI [1.08-1.56]), and co-occurring PTSD and depression (OR = 3.95, 95% CI [2.87-5.46]). These associations were generally consistent across past-month binge drinking and heavy alcohol use, as well as cannabis use, illicit substance use, and hazardous use since the MVI. Findings suggest that substance use, particularly heavy alcohol use and hazardous substance use, is prevalent among adults residing in MVI-affected communities. Adults with limited socioeconomic resources, fear of subsequent MVIs, prior criminal victimization, and co-occurring PTSD and depression appear most vulnerable to hazardous substance use and illicit substance use. These results can inform substance use screening and intervention efforts as part of broader community recovery planning.
Substance use disorder (SUD) and substance misuse are commonly reported among survivors of human trafficking. This scoping review identifies current empirical research on substance use treatment, harm reduction, and recovery support services for survivors. Reviewers searched Ovid-Medline All, Embase.com, CINAHL Plus, Scopus, and Web of Science and conducted forward and backward citation searching of studies that included child, adolescent, or adult sex or labor trafficking survivors, tested a specific intervention to promote substance use recovery, and reported substance use disorder or substance misuse-related outcomes. Two reviewers screened title/abstracts, screened full texts, and extracted data. Reviewers coded bibliographic information, participant characteristics, study design, intervention characteristics, and primary substance use-related outcomes. Data elements were narratively summarized. Six studies, published between 2010 and 2025, were included in this review. Two programs were based in specialty courts in the United States for trafficked youth, whereas the other four were multi-modal (housing, health services, basic needs) nonprofit hospital- or community-based programs in the US (n = 3) and Israel (n = 1). Substance use outcomes were defined through self-reported frequency of use (n = 3), case manager-rated measures (n = 2), and case records (n = 1). Few research or evaluation studies were identified that assessed substance use-related outcomes for survivors in treatment programs. Standardized assessments of substance use, context of use, and related problems were not commonly used. Evaluation of evidence-based psychosocial interventions for SUD is warranted to identify potential adaptations that would support substance use recovery among survivors. People who have been exploited or trafficked are at risk for having problems related to using alcohol and other drugs. In this study, the research team reviewed existing studies of alcohol or drug treatment programs for trafficking surivors. The researchers searched scientific databases for studies that reported alcohol or drug use outcomes for trafficking survivors. Although over 400 unique studies were screened, only six studies reported alcohol or drug use outcomes for trafficking survivors. Studies were published between 2010 and 2025 and included 668 participants who were, on average, 16 years old. Nine out of 10 participants were female. Participants were from diverse races and ethnicities. Participants received services though a hospital-based program, two programs were delivered through courts, and three programs were delivered through community organizations. All programs offered case management to support survivors in meeting their health and basic needs. Substance use outcomes were self-reported by participants, rated by case managers, or collected through treatment records. Some programs saw an improvement in substance use outcomes, whereas others did not see any change. However, more research is needed to understand what works to support trafficking survivors who have difficulties with their alcohol or drug use.
A 2017 systematic review and 2021 update identified 114 studies regarding gabapentinoid (gabapentin and pregabalin) misuse, dependence, or overdose. We aimed to update previous systematic reviews and describe new insights regarding gabapentinoid misuse. PubMed was searched from 1 September, 2020 to 24 January, 2025 using the following four searches: "gabapentin [MeSH] OR pregabalin [MeSH] OR gabapentinoid AND" one of the following four substance misuse-related terms: "substance-related disorders [MeSH]," "overdose," "abuse," or "misuse." Additional research was identified by reviewing papers cited by included studies. Studies presenting novel data regarding gabapentinoid misuse, dependence, or overdose were included. Non-English articles, review articles, and animal studies were excluded. One hundred studies (87 observational, 13 case reports/series) were included, from North America (33), Europe (39), Asia (20), Australia (7), and Africa (1). Sixteen studied gabapentin, 20 pregabalin, and 51 both medications. These studies corroborated previous findings that gabapentinoids are misused both for therapeutic and non-therapeutic purposes, often in conjunction with opioids or other substances, and commonly in people with substance use disorders and psychiatric conditions. Recent research built on the previous systematic review, providing more robust evidence that concomitant use with opioids or benzodiazepines increases overdose risks. New studies also highlight a growing body of evidence regarding misuse within the Middle East and North Africa, among adolescents, and in patients with chronic pain. Newly published evidence demonstrated that gabapentinoid misuse remains a significant concern, including in several populations not often highlighted in previous research. It provides more compelling evidence that gabapentinoids increase overdose risk, particularly when used with opioids or benzodiazepines.
Patients with advanced cancer frequently experience pain and psychological distress, often requiring controlled substances such as opioids and benzodiazepines. Although access to these medications increases risk of substance misuse, little is known about how clinicians and patients discuss controlled substance use during cancer care. Understanding these conversations may inform safer prescribing, improve patient outcomes, and support management of substance use disorder (SUD) risk. We aimed to characterize discussions of controlled substance use in oncology visits, including who initiated conversations, clinician responses, and verbalized SUD risk factors. Five coders reviewed 826 audio-recorded oncology visits from a prior clinical trial. Encounters were coded for substance type, initiator (patient, clinician, both, neither), clinician/patient response style (avoidant, concerned/emotional, engaged, neutral, resistant), and substance misuse risk factors. Mean patient age was 59.5 years; most were female (55.8%), White (81.7%), and married (71.7%). Substance-related content appeared in 14.6% of counters (n = 121; 92 unique patients). Mentioned substances included opioids and sedative-hypnotics (benzodiazepines/sleep aids), with oxycodone referenced in 67 visits. Patients initiated discussions more frequently (n = 51) than clinicians (n = 33), though not significantly, χ2(1, N = 95) = 33.00, p = 0.078. For the remaining encounters, neither initiated (n= 24) or both initiated (n=13). Among patient-initiated discussions, clinician response types were engaged (n = 25), neutral (n = 10), avoidant (n = 12), concerned/emotional (n = 1), or resistant (n = 3). Common substance misuse risk factors included inadequate pain management (n = 28), medication concerns (n = 17), dose escalation (n = 11), psychological concerns (n = 11), and substance misuse/drug-seeking (n = 5). Despite widespread prescribing of controlled substances in oncology, discussions remain infrequent, and clinician responses to SUD-related concerns are often insufficient. These findings highlight opportunities to improve communication and risk management in cancer care.
To assess the prevalence, patterns, and consequences of ADHD stimulant medication misuse among adults in the United States. PubMed and PsycINFO were searched for US-based studies from 2004 to 2024. Cross-sectional and longitudinal studies on stimulant medication misuse among adults were included. Risk of bias was assessed using the Joanna Briggs Institute (JBI) checklist for prevalence studies and the Quality in Prognosis Studies (QUIPS) tool for longitudinal designs. Data were summarized narratively. Sixty-four studies met inclusion criteria, including several high-quality federally funded national surveys. Many other incidence and prevalence studies were conducted at universities; these had inconsistent quality due to low response, non-representative samples, or unclear methodology. National surveys show that past-year misuse among adults is declining, with 2023 estimates ranging from 1.4% to 3.7% among young adults and 1.9% among adults of all ages. Misuse is most prevalent among younger, White, metropolitan-dwelling individuals, and among college students. Misuse is primarily oral and infrequent, although a subset of high-frequency users obtain stimulants from physicians or dealers and exhibit higher rates of polysubstance use. Consequences of misuse may include psychiatric admission, emergency department visits, and illicit drug use. Long-term studies do not support a link between prescribed stimulant treatment in adolescence and later substance use disorder; unfortunately, no studies collected data on long-term physical health consequences. ADHD stimulant medication misuse among adults, although declining, remains a public health concern, particularly among high-frequency users. Research gaps remain, especially regarding long-term health outcomes.
Background and objectives Pregabalin, an antiepileptic drug with anxiolytic and analgesic properties, has been increasingly misused for recreational purposes. This article aimed to assess the extent and patterns of pregabalin misuse in India from a global perspective using pharmacovigilance data. Methods A retrospective post-market observational study was conducted using VigiBase reports on pregabalin-related adverse drug reactions between January 2011 to April 2024. Data extraction and analysis were performed between April to May 2024. Relevant reports were identified using MedDRA term and analysed at global and Indian levels. Results Among 40,582,030 adverse drug reactions (ADRs) in VigiBase, 163,476 involved pregabalins globally. Of these, 8,058 pregabalin abuse-related reports were identified, mainly intentional product misuse (n=3,560; 44.17%), intentional product use issue (n=2,203; 27.34%), and drug abuse (n=1,701; 21.11%). Globally, the USA reported the higher number of pregabalins ADRs, (n=96,867; 59.2%), followed by the Republic of Korea 9.4%, Japan 3.8% and France 3.6%. In India, 50 pregabalin-abuse reports were identified; of which drug abuse (n=26, 52%), intentional overdose (n=13, 26%), intentional product misuse (n=13, 26%), intentional product use-issue (n=4, 8%) and substance use disorder (n=1, 2%) were reported in patients within 18-44 yr (n=36, 72%) and predominantly in males (n=45, 90%). About 94% of reports were deemed serious, with 54% (n=27) requiring prolonged hospitalisation. Interpretation and conclusions Pregabalin misuse in India is prevalent, especially among adult men, and is often associated with serious outcomes. These findings emphasise the urgent need for stricter regulation and targeted interventions to limit misuse and reduce associated risks.
Background: Adverse childhood experiences (ACEs) are associated with adolescent substance use. However, the influence of individual ACEs after controlling for concurrent ACEs is understudied. Methods: Using longitudinal data from the Future of Families and Child Wellbeing Study (n = 3200), we evaluated binary logistic models to test associations from 11 individual ACEs at ages 3-9 (physical abuse; emotional abuse; neglect; housing instability; food insecurity; community violence; parental depression, problematic substance use, intimate partner violence [IPV], incarceration, and death) to adolescent cigarette, marijuana and heavy alcohol use at age 15, while controlling for sociodemographic characteristics and co-occurring ACEs. Results: Marijuana use was associated with neglect (aOR = 1.67, 95% CI = 1.08, 2.61) and parental mental illness (aOR = 1.28, 95% CI = 1.01, 1.62). Heavy alcohol use was associated with emotional abuse (aOR = 2.59, 95% CI = 1.23, 5.48). No ACEs were individually associated with cigarette use. Conclusions: Findings suggest a narrow set of ACEs may be driving well-documented associations between composite ACE indices and substance use outcomes. Emotional abuse may be a singularly salient risk factor for adolescent heavy alcohol use. Neglect and parental mental illness may be stronger risk factors for adolescent marijuana use. Findings provide guidance for tailored interventions and suggest composite ACE indices may incorrectly estimate adolescents' risk for substance use.
To systematically map and synthesise the scientific literature on substance use patterns among elite athletes, encompassing recreational substances, performance-enhancing drugs (PEDs) and polysubstance use. This study was a scoping review conducted in accordance with the Joanna Briggs Institute (JBI) methodological framework and reported following the Preferred Reporting Items for Systematic Review and Meta-Analysis extension for Scoping Reviews (PRISMA-ScR) guidelines. The review protocol was prospectively registered on the Open Science Framework. A comprehensive search was conducted in PubMed/MEDLINE, PsycINFO, Scopus and SportDiscus from inception to March 2025. Eligible studies were peer-reviewed original research articles examining substance use, misuse or substance use disorders among elite athletes, including collegiate, professional, Olympic, Paralympic or national-level competitors. Both recreational substances (eg, alcohol, cannabis, nicotine, prescription drugs) and PEDs were included. From 3292 unique records screened, 119 studies met inclusion criteria. Alcohol was the most extensively studied substance, particularly among National Collegiate Athletic Association collegiate athletes, with consistent evidence of heavy consumption in certain sports, especially those with strong social and team-based norms. PED studies revealed marked sport-specific patterns, largely informed by anti-doping surveillance data, but offered limited insight into psychosocial mechanisms. Research on other substances and polysubstance use was heterogeneous, fragmented, and methodologically variable. Across all domains, the literature was dominated by cross-sectional designs, self-reported data and Western populations. The existing evidence base demonstrates substantial substance-related vulnerability among elite athletes but is characterised by significant conceptual, methodological and geographical gaps. Future research should prioritise longitudinal and theory-driven designs, broader representation of professional and non-Western athletes, integration of mental health frameworks and rigorous evaluation of prevention and intervention strategies. The review protocol was prospectively registered on the Open Science Framework (OSF) (DOI: 10.17605/OSF.IO/3PJDN) on 8 January 2025.
Adolescent substance use is a critical public health issue in rural and American Indian communities with disparities persisting into young adulthood. This study examines motivations for nonuse as predictors of substance use trajectories among adolescents in a computerized Screening and Brief Intervention in 10 high schools on and near the Cherokee Nation Reservation. Low-risk students (n = 360) reported their motivations for nonuse during the initial Screening and Brief Intervention session, and substance use outcomes (alcohol, cannabis, prescription opioid misuse, vaping) were assessed in subsequent surveys. Results from longitudinal growth curve models indicated that most motivations for nonuse were not associated with differential trajectories of substance use over time. One notable exception was "having positive people in one's life," which predicted a significantly lower likelihood of nicotine vaping at the initial follow-up, followed by a faster increase in vaping over subsequent semesters. In secondary wave-specific models, this motivation also predicted reduced cannabis use at the first follow-up, whereas endorsing "it makes me feel bad" predicted higher cannabis use. Reinforcing positive social influences and addressing negative feelings may be an important part of prevention strategies like Screening and Brief Intervention. This study offers new evidence on motivations for nonuse to inform the design of digital prevention tools for underserved rural youth.
Sexual minority male adolescents experience disproportionate health risks compared to heterosexual peers, yet anabolic-androgenic steroid (AAS) misuse in this population remains understudied. This scoping review aimed to synthesize existing literature on AAS misuse among sexual minority male adolescents. This scoping review was guided by Joanna Briggs Institute methods and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review extension. In September 2025 and April 2026, PubMed, EMBASE, and APA PsycInfo were searched without date limits. Eligible studies were peer-reviewed, original research published in English that examined AAS misuse among sexual minority male adolescents. For each included study, authorship, publication year, study location, data source, sample size and demographics, measures of sexual orientation, measures of AAS misuse, and key findings were charted. Seven studies met the inclusion criteria, five of which relied on Youth Risk Behavior Survey data collected between 2005 and 2015. Across studies, sexual minority male adolescents consistently reported higher AAS misuse than heterosexual male adolescents, with particularly elevated prevalence among Black and Hispanic/Latino youth. The literature on AAS misuse among sexual minority male adolescents is limited and largely dependent on older surveillance data. Although misuse appears to have declined over time, prevalence remains elevated, especially among racial and ethnic subgroups. Future research should prioritize updated survey statistics and incorporate qualitative and thematic approaches to better characterize the influences shaping AAS misuse among sexual minority male adolescents.
Objective: Mental and behavioral disorders due to psychoactive substance use, as defined by ICD-10 codes F10-F19, include a spectrum of substance use disorders such as acute intoxication, withdrawal, harmful use, and dependence related to alcohol, opioids, stimulants, cannabis, tobacco, and other substances. These conditions significantly increase the risk of suicide, yet national trends in suicide-related mortality among affected individuals remain underexplored. This study aimed to evaluate national trends in suicide and self-harm mortality among individuals with these disorders from 1999 to 2023. Methods: We conducted a retrospective analysis of U.S. death certificate data from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) database (1999-2023). Decedents with mental and behavioral disorders due to psychoactive substance use were identified using ICD-10 codes F10-F19, encompassing acute intoxication, withdrawal, harmful use, and dependence. Suicide and self-harm deaths were defined by ICD-10 codes U03, X60-X84, and Y87. Age-adjusted mortality rates (AAMRs) per million and average annual percentage changes (AAPCs) were estimated using Joinpoint regression. Analyses were stratified by sex, age, race/ethnicity, and metropolitan status. Results: Between 1999 and 2023, 37,473 suicide-related deaths were identified among U.S. individuals with mental and behavioral disorders due to psychoactive substance use. AAMRs increased from 2.2 to 5.7 per million (AAPC: 3.31; p < .01). Males had higher mortality than females (6.6 vs. 2.9), though females had a steeper rate of increase over time. Middle-aged adults had the highest AAMR (8.2), followed by younger (6.9), older adults (3.4) and children and adolescents (1.1). Non-Hispanic (NH) American Indian/Alaska Native individuals (AI/AN) had the highest AAMR (13.5), followed by NH White (6.2), Hispanic/Latino (1.6), NH Black (1.6), and NH Asian/Pacific Islander (API) (1.4). From 1999 to 2000, non-metropolitan areas had higher AAMRs than metropolitan areas (6.5 vs. 4.3), with significant increases in both settings. Conclusions: Suicide-related mortality among individuals with mental and behavioral disorders due to psychoactive substance use has increased significantly increased in the United States from 1999 to 2023, demonstrating substantial disparities by sex, age, race/ethnicity, and geographic region. These findings highlight the critical need for integrated approaches in suicide prevention and substance-related treatment settings.
Background: Cigar/cigarillo smoking and cannabis use frequently co-occur, reflecting overlapping patterns of substance use and shared risk factors. However, little is known about how co-use of cigars/cigarillos and cannabis is associated with sociodemographic factors, as well as preferences for cannabis forms and spending patterns among co-users. Methods: We analyzed data from the second wave of a national longitudinal survey of U.S. adults who reported recreational cannabis use in January 2025 (N = 1,524). The survey included detailed information on past-30-day cigar/cigarillo use, enabling comparisons between cannabis-cigar/cigarillo co-users and cannabis-only users. We compare these two groups by applying logistic regression to examine sociodemographic correlates and product-specific cannabis preferences, and OLS regression to evaluate differences in total cannabis spending. Results: Overall, 8.26% of recreational cannabis adult users also smoke cigars/cigarillos. Compared with White, non-Hispanic cannabis users, Black, non-Hispanic users are five times (p < 0.001) more likely to smoke cigars/cigarillos. Compared with cannabis users with less than high school education, those with some college or a bachelor's degree are less likely to smoke cigars/cigarillos. Cigar/cigarillo smoking among cannabis users is associated with higher use of flowers (OR = 2.16, p < 0.05) and pre-rolls (OR = 2.05, p < 0.01). Cannabis-cigar/cigarillo co-users report significantly $72 higher monthly cannabis expenditures than cannabis-only users. Conclusions: Adult cannabis users who are Black, non-Hispanic and have less than an associate degree are more likely to smoke cigars/cigarillos. Cannabis-cigar/cigarillo co-users are more likely to consume smoking forms of cannabis such as flowers and to spend more on cannabis, suggesting possible increased risks of harm and addiction associated with co-use.
Descriptives and correlates of concept flavor (CF) use across e-cigarettes, nicotine pouches, and other oral nicotine products (ONPs, e.g., nonmedicinal gums/lozenges/mints) were examined among adolescents and young adults (AYAs). AYAs aged 14-25 years old ever having used a tobacco product (N = 987) were surveyed in May-June 2024. AYAs ever using e-cigarettes (n = 684), nicotine pouches (n = 347), or other ONPs (n = 189) completed measures of CF use and other factors for the products they reported using. Analyses included chi-square and t-tests. CF e-cigarette, nicotine pouch, and other ONP use was between 31.8 and 40.2% in AYAs who ever used each respective product; 3.3% reported CF use across all products. Most perceived that CF products used produced non-tobacco sensations (fruity/cooling/minty; 79.5-96.4%). Compared to lifetime nonuse of respective products, lifetime alcohol and cigarette, smokeless, and other tobacco use were associated with CF e-cigarette use; smokeless tobacco use was associated with CF nicotine pouches and other ONPs use. CF e-cigarette use associated with higher e-cigarette use frequency and intensity compared to nonuse. AYA CF use spans several noncombustible nicotine products, produces fruity/cooling/minty sensations, and is associated with higher intensity vaping and substance co-use. Modifying regulatory policies to address CFs might protect AYAs.
Nutritional disorders are common in patients with Alcohol Use Disorder (AUD) or Substance Use Disorder (SUD) and can lead to vitamin deficiencies such as Folate Deficiency (FD). The aim of this study was to investigate folate levels and the presence of FD in AUD or SUD patients by comparing them according to the type of substance used. A total of 633 AUD or SUD patients were included in this retrospective file review study. Patients were divided into four groups based on the substance they used: Alcohol (n = 217), Cannabinoid (n = 71), Methamphetamine (n = 296) and Opiates (n = 49) and analyzed comparatively in terms of sociodemographic data, folate levels and FD status. In AUD or SUD patients, mean folate levels (H = 110.249, p < 0.001), FD status differ according to the type of substance used (χ2 = 31.715, p < 0.001). Mean folate levels were significantly lower (p < 0.0083) in the Methamphetamine group compared to the Alcohol and Cannabinoid groups, while Possible Folate Deficiency (PFD) was significantly higher in the methamphetamine group (p < 0.0083). FD was significantly higher in the Alcohol, Methamphetamine and Opiate groups compared to the Cannabinoid (p < 0.0083). FD status in AUD or SUD patients varies according to the type of substance used. In these patients, especially those in the methamphetamine group and the alcohol and opiate groups, improving nutrition and folic acid supplementation may contribute to recovery.
In 2019, approximately 21 million children in the United States lived with a parent who misused substances, and over 2 million lived with a parent with a substance use disorder (SUD). While parents with SUD are often invested in preventing intergenerational transmission of substance use, there has been little research devoted to addressing this challenge particularly among parents of adolescents. In this narrative review of existing literature, we take a bioecological perspective that includes individual, interpersonal, and societal factors that offer opportunities for intervention. Specifically, we suggest that there is a need to consider key developmental tasks of adolescence-establishing a sense of autonomy, developing personal identity, and cultivating meaning and purpose-in tandem with effective parenting practices and societal considerations to prevent the intergenerational transmission of substance misuse and use disorders among adolescents when a parent has SUD. We offer specific research recommendations and strategies for leveraging impactful preventative interventions.
Substance use disorders and anxiety are clinically heterogeneous, and broad case-control genetic designs can obscure stage- and subtype-specific biology. A recent series of five transcriptome-wide association study (TWAS) preprints by Cheung examined opioid exposure versus dependence progression, alcohol misuse latent classes, cannabis use disorder, anxiety, and aging-related gene sets. Together, these studies suggest a cross-disorder architecture organized around a Pruning-Plasticity-Aging axis. This synthesis is narrative and hypothesis-generating, because the primary cross-disorder evidence comes from preprints and genetically predicted expression rather than measured patient expression. In this model, liability is not distributed along a single psychiatric-risk continuum. Instead, opioid exposure and some lower-risk or internalizing alcohol profiles appear to involve altered neuroimmune pruning and glial-synaptic refinement, whereas opioid dependence progression, heavier alcohol classes, broad-risk alcohol profiles, and cannabis use disorder show stronger involvement of glutamatergic plasticity, presynaptic adaptation, reward-circuit remodeling, AMP-activated protein kinase-mechanistic target of rapamycin (AMPK-mTOR) nutrient sensing, mitochondrial bioenergetics, and selected nicotinamide adenine dinucleotide (NAD)/sirtuin stress-response branches. Anxiety diverges by loading more strongly on inflammatory-apoptotic signaling, complement/sterile alpha and toll/interleukin receptor motif-containing protein 1 (SARM1)-linked axonal stress, and mitochondrial NAD-stress programmes. The most promising findings include stage-specific opposition in opioid TWAS profiles, latent-class plasticity inversion in alcohol misuse, a triggering receptor expressed on myeloid cells 2 (TREM2)-positive cannabis use disorder profile contrasted with a SARM1/complement C1q C chain (C1QC)-positive anxiety profile, and branch-specific rather than global aging biology. This review synthesizes these findings; places them in established addiction, neuroimmune, and aging biology; and outlines validation priorities for colocalization, fine-mapping, cell-type resolution, and functional testing.
Volatile substance abuse (VSA) continues to cause preventable deaths worldwide. In Australia, petrol sniffing has historically been the main form of misuse in remote Indigenous communities. However, coronial and surveillance data suggest an increasing role of gas fuels and aerosol propellants. Twenty-five VSA-related deaths reported to the Northern Territory (NT) coroner over a 21-year period (2002-2022) were reviewed. In the 22 cases where acute volatile substance inhalation was the direct cause of death, the decedents were all male, and predominantly young Aboriginal individuals aged between 12 and 29 years. Furthermore, petrol vapor inhalation was responsible for most fatalities up to 2018, after which no further petrol sniffing-related deaths occurred. Deaths that occurred after 2018 were associated with the use of propane or butane from aerosol cans, such as those used for deodorants. A public health initiative that resulted from this was the keeping of aerosol deodorants in supermarkets within locked cabinets. In conclusion, public health interventions, such as the introduction of Opal fuel in remote communities in the NT, have been effective, with a sharp decrease in petrol sniffing-related fatalities. However, this seemed to have led to a shift towards the use of other inhalants, most commonly butane and/or propane inhaled from aerosol canisters. Forensic practitioners should be alert to non-petrol volatiles, and public health strategies need to broaden beyond petrol substitution to include regulatory and community-level measures addressing gas fuels and aerosols.
Coping strategies and health-related quality of life (HRQoL) are critical psychosocial determinants of substance use risk during emerging adulthood. These factors may be particularly salient among young women due to gendered emotional and interpersonal stressors. However, much substance use research remains gender-neutral, often failing to account for unique developmental factors influencing women. This study aims to identify gender-sensitive coping-well-being profiles associated with alcohol and cannabis co-use among young adult women and examine whether specific coping strategies and HRQoL domains predict hazardous involvement. Participants were 140 community-recruited women (ages 18-30; M = 21.3). Validated self-report measures included the Alcohol Use Disorders Identification Test (AUDIT), Cannabis Abuse Screening Test (CAST), Coping Strategies Inventory (CSI), and the 36-Item Short Form Health Survey (SF-36). Analyses utilized ANOVA/MANCOVA, regression models, and two-step cluster analysis. Alcohol use was prevalent (92.5%), with 25% reporting alcohol and cannabis co-use. Greater cannabis-related risk was associated with higher alcohol involvement, increased self-critical coping, and higher scores on SF-36 Bodily Pain. Three distinct profiles emerged: High-Risk (co-use, elevated self-criticism, low general health, and reduced social support), Protective (strong problem-solving, social support, and higher HRQoL in key psychosocial domains), and Latent Vulnerability (low substance use despite poor coping resources, high self-criticism, and reduced mental well-being). Coping strategies and perceived well-being differentiate women's substance involvement beyond usage frequency. Gender-sensitive prevention should address self-critical coping and HRQoL, even among women with low current use but high psychosocial vulnerability. Psychosocial profiling may improve early identification for co-use risk.
Individuals who engage in illicit or nonmedical opioid use may have elevated risk of health and social consequences, including progression to opioid use disorder (OUD). Preventive interventions to reduce this risk are lacking. This trial tested the impact of a primary care-integrated collaborative care approach for reducing risky opioid use, defined as nonmedical use of prescription opioids or any use of illicit opioids. Cluster-randomized controlled trial randomized primary care providers (PCPs) and their patients into the Subthreshold Opioid Use Disorder Prevention (STOP) intervention or enhanced usual care (EUC). Primary care clinics at 5 U.S. sites. PCPs and their patients were recruited January 2021-May 2023. A total of 119 PCP clusters (STOP = 48, EUC = 51) and 202 patients (STOP = 88, EUC = 114) enrolled. Eligible patients were adults (≥18 years) having current risky opioid use, without moderate-severe OUD. Patient participants were majority female (63.4%), white (70.8%) and non-Hispanic (96.5%), with a mean age of 55.7 [standard deviation (SD) = 12.7] years. At baseline, 63.4% of participants had moderate-severe pain (Brief Pain Inventory) and below average physical (79.2%) and mental (62.4%) health (SF-12). The STOP collaborative care intervention consisted of brief advice from the PCP about reducing risky opioid use, meetings with a clinic-embedded nurse care manager over 12 months and remote health coaching (2-6 sessions). Both groups received primary care treatment as usual and overdose risk reduction materials. The primary outcome was total days of risky opioid use, recorded from 6 monthly electronic surveys. A key secondary outcome was moderate-severe OUD at 6 and 12 months. A total of 77 (87.5%) STOP and 107 (93.9%) EUC participants completed the 6-month assessment period. The primary outcome analysis used the Intention-to-Treat sample with multiple imputations of missing data. Mean days of risky opioid use at 180 days were lower in STOP than EUC [12.2 (SD = 27.73) vs. 15.5 (SD = 32.64)]; the difference between groups adjusted for baseline risky opioid use was not statistically significant (rate ratio 0.95, 95% confidence interval = 0.52-1.74). One STOP participant (1.1%) and 13 EUC participants (11.4%) developed moderate-severe OUD at 6 months, and 3 (3.4%) STOP and 6 (5.3%) EUC participants had moderate-severe OUD at 12 months (P < 0.001). This cluster-randomized controlled trial did not find evidence that the STOP intervention for reducing risky opioid use produced greater reductions over 6 months compared with enhanced usual care, though fewer intervention participants progressed to moderate-severe opioid use disorder. Patients had a high burden of pain and comorbidities that may present challenges to reducing opioid use.