Concurrent use of heroin and cocaine (known as the \"speedball\") prevails among substance use disorder populations, especially in opioid-dependent individuals, with severe consequences and a high fatality rate. Little is known about the patterns and correlations of the concurrent use of heroin and cocaine. It is vital to investigate such a polydrug use in both humans and animals to uncover concomitant toxicity and the cause of fatal overdose (death). In this study, we aimed to shed some light on the role of cocaine in the etiology of heroin-related deaths in the context of molecular pharmacokinetics (PK). For the purpose, a high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of heroin, cocaine, and their metabolites in whole blood was developed and fully validated in accordance with the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. Then, this method was used to analyze heroin, cocaine, and their metabolites in blood from the rats intraperitoneally administered non-lethal 10 mg/kg heroin or 20 mg/kg cocaine alone, or their combination that is lethal with a proximal mortality of 33 %. The obtained results from the rats that experienced the lethal toxicity revealed that the concurrent use of heroin and cocaine significantly increased the risk of fatality from overdose. Heroin significantly slowed down the elimination of cocaine and its main metabolites in blood, while cocaine significantly enhanced heroin metabolism from 6-monoacetylmorphine (6-MAM) to morphine. Similar elimination half-lives for other heroin metabolites were observed. These findings are reported for the first time in this study, facilitating our understanding of the polysubstance metabolism and severe consequences produced by the polydrug use.

BACKGROUND: There are no clinical practice guidelines addressing the treatment of tobacco-cannabis co-use and a dearth of studies to inform treatment for co-use. This narrative review aims to (1) summarize promising intervention components used in published co-use treatment studies, (2) describe key gaps and emerging issues in co-use, and (3) provide recommendations and considerations in the development and evaluation of co-use interventions.
METHODS: We conducted a literature search in June 2024 across several databases to update previous reviews on tobacco-cannabis co-use treatment. We found 9 published intervention studies that specifically addressed treatment for both substances. Data from these studies were manually extracted and summarized.
RESULTS: Most of the 9 included studies (1) focused on acceptability and/or feasibility, (2) provided both psychosocial/behavioral and pharmacotherapy intervention components, (3) were conducted in adults, and (4) were delivered in-person, with some having digital asynchronous components, for a 5-to-12-week duration. The most common psychosocial/behavioral strategies used were Cognitive Behavioral Therapy, Motivational Interviewing, and Contingency Management; while the most common pharmacotherapy was Nicotine Replacement Therapy. There was no evidence of compensatory use of tobacco or cannabis when providing simultaneous treatment for both substances.
CONCLUSIONS: The literature to date provides support for well-integrated multi-component interventions of psychosocial/behavioral and pharmacotherapy strategies for co-use treatment. This review reinforces an urgent need for treatments targeting tobacco and cannabis co-use. Future interventions should address key gaps, including co-use of vaporized products among youth and young adults, tailored interventions for priority populations, and digital applications to increase reach and advance health equity.

BACKGROUND: Most studies examining the simultaneous use of cannabis with other drugs have focused on cannabis and alcohol, with fewer studies examining simultaneous use of cannabis with other drugs. The United States is currently experiencing an upward trend in psychedelic use and there is an increasing need to characterize cannabis and psychedelic drug interactions to best inform public health recommendations.
METHODS: A mixed methods field study design was used to survey participants (N = 128) on their lifetime co-use of cannabis with other drugs. Participants who reported lifetime co-use of cannabis and psychedelics (N = 63) were then asked open-ended questions about their most recent simultaneous co-use experience (i.e., how cannabis enhanced their psychedelic experience and whether they experienced any adverse reactions). We conducted a thematic analysis of responses describing how cannabis enhanced the psychedelic experience (N = 54). However, due to low response rate for participants reporting an adverse reaction (N = 7, 11.1%), responses to this question were not analyzed thematically and are instead presented individually.
RESULTS: Themes included tension reduction and balancing of drug effects (N = 27, 50%), enhancement to psychological processes (N = 11, 20.4%), intensified psychedelic drug effects (N = 12, 22.2%), enhanced psychedelic come-down experience (N = 8, 14.8%), and overall ambiguous enhancement (N = 7, 13%). Among participants reporting an adverse reaction, individual responses included increased anxiety and intensity of the experience, decreased sociability, increased negative affect, sleepiness, disassociation, and confusion.
CONCLUSIONS: Additional research is warranted to better characterize cannabis and psychedelic drug interactions to best inform public health recommendations.

Polysubstance use is associated with myriad short- and long-term health outcomes. Although prior research has documented differences in polysubstance use between lesbian, gay, bisexual, transgender, queer/questioning, and other sexual and gender minoritized (LGBTQ +) youth and their heterosexual/cisgender counterparts, as well as between subgroups of LGBTQ + youth, it is unknown how personal, family, and school factors are associated with substance use patterns among LGBTQ + youth. Using a large, national sample of 9646 LGBTQ + youth ages 13-17, we used latent class analysis to examine patterns of alcohol, tobacco, and marijuana use and to determine whether personal, family, and school factors predict class membership. We identified five classes of substance use: polysubstance use, polysubstance experimentation, dual alcohol and cannabis, alcohol, and no use. Greater depression and LGBTQ + victimization, and an ability to be oneself at school, were associated with greater odds of membership in the polysubstance use class, while higher levels of family connection and having a Gender Sexuality Alliance (GSA) at school were associated with lower odds of membership in the polysubstance use class. Our analysis also revealed sociodemographic differences in class membership. These findings highlight potential mechanisms for intervention to reduce polysubstance use among LGBTQ + youth.

OBJECTIVE: This study assessed the direct and indirect effects (via depressive symptoms) of lifetime use of a broad range of substances on suicide risk among US adolescents.
METHODS: This was a cross-sectional study.
METHODS: Data from the 2021 Youth Risk Behavior Survey were used (N = 12,303, 48.7% female). Associations between five types of substance use (cigarette, e-cigarette, alcohol, marijuana, and prescription pain medicine) and three dimensions of suicide risk (suicidal ideation, suicide plan, and suicide attempt) were measured by multivariate logistic regression models. The role of depressive symptoms was further examined by structural equation modeling.
RESULTS: Almost three in five (57.5%) adolescents had used one or more substances in their lifetime (18.1% one type, 12.2% two types, 13.1% three types, 10.2% four types, and 3.8% five types). Adolescents using five substances were up to 16 times more likely to experience suicidal ideation and behaviors. Depressive symptoms significantly linked the pathway from substance use to suicide risk, resulting in much stronger indirect effects than the direct effects. Collectively, the five substance use behaviors and depressive symptoms explained about 60.4% of variance in suicidal ideation, 53.6% of variance in suicide plan, and 55.0% of variance in suicide attempt.
CONCLUSIONS: Lifetime use of multiple substances is significantly correlated with suicidal ideation and behaviors among adolescents via the pathway of depressive symptoms. Routine screening for a broad range of substance use behaviors is needed to identify adolescents at risk for suicide and accessible mental health services could potentially attenuate the linkage between substance use and suicide risk.

With the continued rise of polysubstance use throughout the country, it has been shown to affect a multitude of organ systems. Drug-induced liver injury (DILI) has been widely documented in its association with salicylates or acetaminophen and the utility of using N-acetylcysteine (NAC) for its hepatoprotective effects. However, DILI caused by illicit drug use and guideline-directed management has had little research. We present the case of a 29-year-old female who presented with altered mental status. She was found to have a concomitant liver injury and was treated supportively without the use of NAC, with gradual improvement.

BACKGROUND: Polysubstance use is associated with adverse health outcomes, yet little research has measured changes in polysubstance use. We aimed to 1) estimate trends in marijuana and heavy alcohol use by cigarette smoking and demographic subgroups, and 2) examine patient factors associated with concurrent use among adults who were smoking.
METHODS: We conducted a repeated cross-sectional analysis of 687,225 non-institutionalized US adults ≥18 years from the 2002-2019 National Survey on Drug Use and Health. Participants were stratified into current, former, and never smoking groups. Main outcomes were prevalence of heavy alcohol use, marijuana use, and concurrent use of both substances.
RESULTS: From 2002-2019, heavy alcohol use declined from 7.8 % to 6.4 %, marijuana use rose from 6.0 % to 11.8 %, and concurrent use of alcohol and marijuana remained stable. Among adults who were smoking from 2005 to 2019, higher education was associated with higher odds of heavy alcohol use, while older ages, female gender, non-White race/ethnicity, and government-provided health insurance were associated with lower odds. The odds of marijuana use decreased in females, older ages, and higher incomes while increasing in people with poorer health status, higher education, government-provided or no health insurance, and serious mental illness. Compared to White adults who were smoking, Black counterparts had higher odds of marijuana use (OR=1.23; 95 %CI: 1.15-1.29), while Hispanic (OR=0.68; 95 %CI: 0.63-0.72) and other racial/ethnic identities (OR=0.83; 95 %CI: 0.77-0.90) had lower odds.
CONCLUSIONS: Our study suggests marijuana use might not be sensitive to changes in the use of tobacco and alcohol.

This study used the National Survey on Drug Use and Health to assess a nationally representative sample (N = 4596) weighted to represent 35.2 million adults with DSM-5 criteria-determined substance use disorders (SUDs). This study explored substance use treatment utilization in 2020, emphasizing populations with high vulnerability (e.g., criminal justice involvement (CJI) through parole or probation, polysubstance use, severe mental illness, and HIV/STI). Substance use treatment was broadly defined (any inpatient, outpatient/doctor\'s office, self-help/other for alcohol/drugs). Our results indicated that among adults with SUDs in 2020, 7 million (20%) had multiple SUDs, 1.75 million (5%) had CJI, 5.3 million (15%) had a severe mental illness, and 1.8 million (5%) had a diagnosis of HIV/STI in the last year. Only 7% of individuals with SUD sought any substance use treatment in the past year. CJI (aOR: 13.39, 95% CI: [7.82, 22.94]), serious mental illness (aOR: 3.27, 95% CI: [1.93, 5.55]), and having both 2 (aOR: 2.10, 95% CI: [1.29, 3.42]) or 3 or more SUDs (aOR: 3.46, 95% CI: [1.82, 6.58]) were all associated with a greater likelihood of receiving treatment. Marriage (aOR: 0.43, 95% CI: [0.25, 0.74]) and having an income twice the poverty threshold (aOR: 0.53, 95% CI: [0.29, 0.94]) were associated with reduced odds of receiving any substance use treatment. Compared to those 18 to 25, older individuals had increased odds (2-4 times) of receiving treatment. Interventions are crucially needed to increase access to treatment among those with SUDs.

BACKGROUND: Acute substance intoxication is associated with traumatic injury and worse hospital outcomes. The objective of this study was to evaluate the association between simultaneous opioids and benzodiazepines (OB) use and hospital outcomes in elderly trauma patients.
METHODS: We performed a retrospective analysis using the American College of Surgeons Trauma Quality Improvement Program (ACS-TQIP) 2017 database. We included trauma patients (age ≥ 65 years) examined by urine toxicology within 24 hours of presentation. The primary outcome was in-hospital mortality. Secondary outcomes included hospital and ICU lengths of stay (HLOS AND ICULOS), in-hospital complications (eg, ventilator-associated pneumonia), unplanned intubation, and duration of mechanical ventilation. Patients were stratified being both positive for opioids and benzodiazepines (OB+) or not (OB-) based on having positive or negative drug screen for both drugs, respectively. A 1:1 propensity score matching was performed controlling for demographics (eg, age and sex), comorbidities (eg, alcoholism), and injury characteristics.
RESULTS: Of 77,311 tested patients, 849 OB+ were matched to OB- patients. Compared to OB- group, OB+ patients were more likely to have unplanned intubation (26 [3.1%] vs 8 [0.9%], P = 0.002) and had prolonged HLOS (≥2 days: 683 [84.0%] vs 625 [77.8%], P = 0.002). There were no differences in all other outcomes (P > 0.05).
CONCLUSIONS: The OB intake is associated with higher incidence of unplanned intubation and longer HLOS in elderly trauma patients. Early identification of elderly trauma patient with OB+ can help provide necessary pharmacologic and behavioral interventions to treat their substance use and potentially improve outcomes.

BACKGROUND: Polysubstance use is a highly prevalent public health issue, particularly among adolescents, and decisions on prevention programming and policies are often made at the local level. While there is a growing literature examining patterns of polysubstance use among adolescents, little is known about differences in those patterns across geographic regions.
METHODS: Using a large, representative sample of high school students from the state of Maryland (n = 41,091) from the 2018 Maryland Youth Risk Behavior Survey, we conducted a latent class analysis (LCA) of adolescent substance use along nine binary indicators, including past 30-day combustible tobacco, e-cigarette, alcohol, and cannabis use, as well as lifetime use of prescription opioids, cocaine, heroin, methamphetamine, and injection drug use. Measurement invariance across counties was examined using the Multiple Indicators and Multiple Causes (MIMIC) procedure.
RESULTS: The results of the LCA show three classes of adolescent substance use for the total sample: (1) low substance use, (2) commonly used substances (i.e., e-cigarette, alcohol, and cannabis use), and (3) polysubstance use. The results from the MIMIC procedure demonstrated geographic differences in students\' endorsement of specific indicators and their class membership.
CONCLUSIONS: These differences demonstrate the need for an examination of local trends in adolescent polysubstance use to inform multi-tiered prevention programming and policy.