Journal: JAMA Network Open, 2026, doi: 10.1001/jamanetworkopen .2026.9842
Authors: C. Austin Zamarripa, Spencer Lin, McKenna Klausner, Kriti Rastogi, Daniel J. O. Roche, Matthew Novak, … Tory R. Spindle
Abstract:
Importance: Simultaneous cannabis and alcohol use (co-use) is a public safety concern. Controlled data on the effects of co-ingestion of oral cannabis products (edibles) with alcohol are lacking, despite an increased prevalence of this behavior.
Objective: To evaluate the individual and interactive effects of cannabis edibles and alcohol on simulated driving and subjective and objective impairment measures.
Design, Setting, and Participants: This within-participant, double-blind, double-dummy crossover study of healthy adults included 7 outpatient sessions, separated by 1 week, at Johns Hopkins University School of Medicine from February 2022 to August 2025.
Intervention: Brownies containing 0 mg, 10 mg, or 25 mg Δ9-tetrahydrocannabinol (THC) combined with placebo drinks or alcohol-containing drinks, calculated to achieve breath alcohol concentrations (BrACs) of 0%, 0.05%, or 0.08%.
Main Outcomes and Measures: Driving outcomes included the global drive score (GDS), a composite index of multiple driving measures, and the standard deviation of lateral position as the main outcomes. Other outcomes included cumulative impairment clues on standardized field sobriety tests (SFSTs), subjective drug effects, cognitive and psychomotor performance (using the DRUID [Driving Under the Influence of Drugs] application), and blood cannabinoid concentrations.
Results: Participants included 25 healthy adults (15 males [60%]; mean [SD] age, 25.6 [4.9] years) who reported recent binge drinking, prior cannabis and alcohol co-use, and fewer than 3 cannabis uses per week. Compared with placebo, all active drug conditions except 10 mg THC negatively impacted driving performance (ie, GDS). Driving impairment from alcohol alone at 0.08% BrAC was comparable with that of 0.05% BrAC and 10 mg THC (mean [SD] GDS, 1.6 [1.6] vs 1.6 [1.4]) and significantly lower than 0.05% BrAC and 25 mg THC (mean [SD] GDS, 2.5 [1.7]; P = .02). Driving impairment and subjective intoxication (eg, confidence to drive) were often greater under co-use conditions compared with cannabis or alcohol alone. Relative to placebo, SFST performance worsened at 0.08% BrAC (mean [SD] score, 2.2 [2.2] vs 0.2 [1.3]; P = .008) but not in several other conditions in which marked driving decrements were observed. THC and metabolite pharmacokinetics were not influenced by alcohol.
Conclusions and Relevance: In this crossover trial of healthy adults who co-used cannabis and alcohol, cannabis edibles combined with alcohol augmented driving impairment. The legal alcohol intoxication limit in most of the US (0.08% BrAC) may be too liberal if a driver has co-used cannabis and alcohol. In this era of expanding cannabis legalization, there is a pressing public health need for improved impairment detection strategies and consideration of cannabis and alcohol co-use in policies dictating access to these substances.
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Journal: Molecular Psychiatry, 2026, doi: 10.1038/s41380-026-03618-z
Authors: Beth Han, Nora D. Volkow, Christopher M. Jones, Deborah Dowell, Grant Baldwin, Emily B. Einstein, … Wilson M. Compton
Abstract:
Polysubstance use disorders ( ≥ 2 substance use disorders (SUDs)) are associated with high morbidity and mortality. We analyzed data from 92,233 adult participants in the 2022–2023 US National Surveys on Drug Use and Health to estimate past-year prevalence of polysubstance use disorders and to examine their associations with age of substance use initiation. Multivariable logistic regression and Poisson regression were applied. Age- and sex-adjusted past-year prevalence of 2 SUDs was 19.2–44.9% (95% CIs=11.1–62.3%) among adults with any SUD. Age- and sex-adjusted past-year prevalence of ≥3 SUDs ranged from 16.4% (95% CI = 14.3–18.6%) among adults with cannabis use disorder, to 32.4–44.7% (95% CIs=29.1–51.3%) among those with opioid use disorder or prescription stimulant or tranquilizer/sedative use disorder, and up to 48.2–72.0% (95% CIs=39.4–81.7%) among those with methamphetamine, cocaine, or hallucinogen use disorder. Overall, compared to adults who initiated substance use before age 18, the number of SUDs was 73–83% lower for those who initiated at age ≥21 (range of incidence density ratios (IDRs)=0.17–0.27, 95% CIs=0.12–0.31). Specifically, compared with corresponding adult counterparts who initiated before age 18, the number of moderate-severe SUDs was 32% lower among those initiating alcohol at ages 21–29 (IDR = 0.68, 95% CI = 0.57–0.83), 21% lower among those initiating cannabis at ages 21–29 (IDR = 0.79, 95% CI = 0.69–0.90), and 45–62% lower (IDRs=0.38–0.55, 95% CIs=0.31–0.76) among adults who never initiated alcohol, cannabis, or nicotine use. The elevated prevalence of polysubstance use disorders associated with early initiation of substance use underscores the critical need for evidence-based strategies to prevent alcohol, cannabis, and nicotine consumption before age 21.
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Journal: medRxiv, 2026, doi: 10.64898/2026.04.14.26349857
Authors: Olivia K. Roberts, Jihyoun Jeon, Evelyn Jimenez-Mendoza, Stephanie R. Land, Neal D. Freedman, Rossana Torres-Alvarez, … Andrew F. Brouwer
Abstract:
Introduction: Monitoring trends in transitions in the use of electronic nicotine delivery systems (ENDS) and cigarettes among youth is important for understanding the potential public health impacts of these products.
Methods: Using a weighted Markov multistate transition model accounting for complex survey design, we estimated transition rates and one-year transition probabilities between never, non-current, ENDS-only, and cigarette use (with or without dual use of ENDS) among 26,744 youth aged 12–17 years who participated in at least two consecutive waves from Waves 2–7.5 (approximately 2015–2023) of the nationally representative Population Assessment of Tobacco and Health (PATH) Study. We also estimated transitions stratified by ages 12–14 and 15–17 years.
Results: The one-year probability of ENDS-only initiation from never use among youth peaked in 2017–19 (Waves 4–5) at 4.0% (95%CI: 3.6–4.3%) and was higher for 15–17-year-olds at 5.8% (95%CI: 5.2–6.4%) than 12–14-year-olds at 2.2% (95%CI: 1.8–2.6%). In the following years, ENDS-only initiation rates declined and plateaued, with 2.6% (95%CI: 2.3–3.0%) initiation in 2022–23. Cigarette initiation from never use decreased over 2015– 23 from 0.8% (95%CI: 0.6–1.0%) in 2015–16 to 0.1% (95%CI: 0.0–0.2%) in 2022–23. There was an increase in the fraction of youth who transitioned from non-current product use to ENDS-only use from 13.7% (95%CI: 7.5–20.0%) in 2015–16 to 35.1% (95%CI: 25.4–44.8%) in 2022–23, paired with a decrease in non-current use to cigarette use from 20.9% (95%CI: 11.8–30.0%) to 6.3% (95%CI: 1.7–10.8%). Transitions from ENDS-only or cigarette use to non-current use remained relatively constant over time at around 25% and 15% per year, respectively.
Conclusion: ENDS-only use initiation has changed over time, peaking around 2019 and subsequently decreasing and plateauing, but cessation rates for both ENDS and cigarettes have remained relatively stable. Thus, interruption of tobacco product initiation may be the most effective approach to reducing tobacco product use among youth.
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Journal: Harm Reduction Journal, 2026, doi: 10.1186/s12954-026-01443-9
Authors: Theresa Anasti, Hilary Thibodeau, Nathaniel A. Dell, Kathleen Preble, Lauren Grimes, & Lindsay B. Gezinski
Abstract:
Background: Drug-related risks such as adverse health outcomes, overdose, and violent victimization vary across populations due to the marginalization of identities, structural inequities, and differing environments. Discrimination and criminalization exacerbate drug-related risks specifically for survivors of sexual exploitation who use drugs. This study aims to understand how survivors who are not currently utilizing intensive treatment services perceive their risk environment, including available resources, and identify possible mechanisms to address health equity. Emphasizing the role of harm reduction and the expertise of lived experience, this paper encourages innovative approaches to supporting survivors.
Methods: A research team conducted seventeen semi-structured interviews with survivors of exploitation who currently or formerly used drugs in a midwestern US state. This project emerged from a larger study exploring how survivors of exploitation navigated substance use treatment services. The team used Deterding and Waters’ twenty-first century flexible coding approach to generate both inductive and deductive codes for data analysis and met weekly to discuss codebook development and code application. The intersectional risk environment framework was used to interpret the findings.
Results: Survivors identified characteristics of the physical, social, policy, and economic risk environments that contributed to increased barriers to obtaining long term health and safety. While most participants had previously accessed intensive services for substance use disorder (SUD), restrictions on geographic mobility, poor medical care, and disproportionate criminal-legal involvement were noted as persistent issues faced by survivors upon leaving SUD services, that contributed to ongoing substance use and health inequities. Barriers across risk environments were compounded by the dual stigmatization of drug use and exploitation and further escalated for those with multiple marginalized identities.
Conclusion: Increasing access to harm reduction for survivors who use drugs requires a multipronged approach that tackles structural drivers of inequities as well as community and individual level stigma and discrimination. Critical, actionable research that accounts for this complexity is needed to advance health equity for this group.
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Journal: Lancet, 2026, doi: 10.1016/S0140-6736(26)00305-3
Authors: Mette Kruse Klausen, Signe Keller Justesen, Julie Niemann Pedersen, Line Rasmussen, Andreas Jensen, Mathias Ebbesen Jensen, … Anders Fink-Jensen
Abstract:
Background: Alcohol use disorder accounts for 5% of deaths worldwide annually, and there is an urgent need for new therapeutic interventions. Preclinical and initial human studies indicate that the GLP-1 receptor agonist semaglutide might reduce alcohol drinking. This study evaluated the efficacy of semaglutide once-weekly in treatment-seeking patients with alcohol use disorder and comorbid obesity.
Methods: In a 26-week, single-centre, randomised, double-blinded, placebo-controlled trial, treatment-seeking participants with moderate to severe alcohol use disorder and comorbid obesity were assigned (1:1) to receive once-weekly semaglutide (2·4 mg subcutaneously) or placebo (saline subcutaneously), in addition to standard cognitive behavioural therapy. The primary endpoint was a reduction in the number of heavy drinking days assessed after 26 weeks of intervention, analysed with an ANCOVA model. Analysis adhered to the intention-to-treat principle, and missing outcome data were addressed using multiple imputations. Safety was assessed in all treated patients. The trial is registered at ClinicalTrials.govNCT05895643, and is complete.
Findings: From June 10, 2023, to Feb 4, 2025, 108 participants (53 women and 55 men) were enrolled, with 54 participants in each of the semaglutide and placebo treatment groups, and all were included in the data analysis. Overall, 88 participants (81%) completed the full intervention. Semaglutide was associated with a reduction in heavy drinking days (-41·1 percentage points from baseline, 95% CI -48·7 to -33·5) compared with placebo (-26·4, -34·1 to -18·6; estimated treatment difference -13·7 percentage points, -22·0 to -5·4; p=0·0015), and had substantial effects on multiple secondary alcohol-related and somatic outcomes. Adverse events were transient, generally mild to moderate gastrointestinal effects, and occurred more frequently in the semaglutide group.
Interpretation: Semaglutide showed robust therapeutic effects in treatment-seeking participants with obesity and alcohol use disorder and this trial supports previous preclinical and clinical findings suggesting GLP-1 receptor agonists as a potential novel treatment target for alcohol use disorder.
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