Research News Roundup: January 15, 2026

Journal: JAMA Network Open, 2026, doi: 10.1001/jamanetworkopen .2025.51563

Authors: Yuji Mizushima, Jonathan Cantor, Ryan K. McBain, Fang Zhang, Alyssa Burnett, Ensheng Dong, … Hao Yu

Abstract:

Importance: Alcohol use disorder (AUD) is a major public health concern; medications for AUD (MAUD) are an effective form of treatment but remain underused. Identifying MAUD access trends and the characteristics of counties with limited availability can inform targeted efforts to expand treatment capacity.

Objective: To examine trends in geographic availability of MAUD at US substance use disorder treatment facilities (SUDTFs) from 2017 to 2023 and assess county characteristics associated with SUDTFs offering MAUD.

Design, setting, and participants: This nationwide cross-sectional study used data from the Mental Health and Addiction Treatment Tracking Repository, which includes longitudinal data on licensed SUDTFs and whether they offer MAUD (acamprosate, disulfiram, or naltrexone), to quantify trends in MAUD availability at SUDTFs from January 2017 to December 2023.

Main outcomes and measures: The primary outcome was a county-year indicator for whether at least 1 SUDTF in the county offered MAUD. Explanatory county variables included rurality, percentage of traffic fatalities involving alcohol, percentage of the population that drank excessively, percentage of uninsured individuals, poverty rate, percentage of individuals over age 65 years, and percentage of non-Hispanic White individuals. Univariate logistic regressions with state and year fixed effects were used to explore associations between county characteristics and the probability that a county had any SUDTFs offering MAUD.

Results: Across 22 000 county-years in a total of 3153 counties, the mean (SD) percentage of counties with at least 1 SUDTF offering MAUD increased from 34.12% (47.42%) in 2017 to 43.88% (49.63%) in 2021, but growth plateaued after 2021. Lower MAUD presence in a county was associated with rural-adjacent (difference, -22.40 percentage points [pp]; 95% CI, -24.43 to -20.38 pp) and rural-remote (-23.64 pp; 95% CI, -25.72 to -21.56 pp) relative to metropolitan county status as well as with a higher poverty rate (-0.66 pp; 95% CI, -0.93 to -0.38 pp), greater percentage of individuals aged 65 years or older (-2.33 pp; 95% CI, -3.02 to -1.65 pp), and higher proportion of non-Hispanic White individuals (-0.58 pp; 95% CI, -0.71 to -0.46 pp), whereas greater prevalence of binge drinking (difference, 1.90 pp; 95% CI, 1.26-2.54 pp) and a higher percentage of college-educated individuals (1.28 pp; 95% CI, 1.13-1.43) were associated with higher MAUD presence.

Conclusions and relevance: In this cross-sectional study, the proportion of SUDTFs offering MAUD increased from 2017 to 2021, but growth then plateaued. Policies supporting the expansion of MAUD-providing facilities, particularly in underserved counties, may be needed to address persistent gaps in access.

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Journal: Journal of Comparative Effectiveness Research, 2026, doi: 10.57264/cer-2025-0171

Authors: Madhusudan Kabra, Tushar Srivastava, Raju Gautam, Janharpreet Singh, Juha Oksanen, Tim MacDonald, … Shijie Ren

Abstract:

Aim: Opioid use disorder (OUD) leads to significant morbidity and mortality. While opioid agonist therapies like transmucosal buprenorphine and methadone are effective, they face challenges such as poor adherence, diversion risk and suboptimal abstinence rates, prompting the development of long-acting injectable (LAI) buprenorphine. However, comparative evidence among LAIs and versus standard treatments remains limited. The aim of this study is to provide comparative evidence among buprenorphine LAIs and versus oral opioid agonist treatments.

Materials & methods: We conducted a systematic literature review and network meta-analysis (NMA) evaluating the effectiveness and safety of LAI buprenorphine treatments (extended-release buprenorphine [BUP-XR; monthly injection] and other BUP-LAI [weekly and monthly injection]) versus transmucosal buprenorphine, methadone and buprenorphine implants in adults with OUD. The review included randomized controlled trials (RCTs) and non-RCTs for LAIs (January 2012 and March 2025). Primary outcomes were treatment discontinuation and illicit opioid use. Secondary outcomes were safety and health-related quality of life. Data were synthesized using univariate NMAs, bivariate NMA with surrogate end point modelling. Studies with limited data and single-arm designs were incorporated by using study-level matching techniques.

Results: Ninety-eight studies met the inclusion criteria. BUP-XR demonstrated the highest probability of achieving treatment retention and opioid abstinence across analyses. In combined evidence (RCTs and non-RCTs), BUP-XR showed significantly lower risk of illicit opioid use versus transmucosal buprenorphine (rate ratio [RR] 1.99; 95% credible interval [CrI]: 1.29-3.11) and methadone (RR: 2.66; 95% CrI: 1.40-3.56). BUP-XR showed borderline significantly lower risk of illicit opioid use versus other BUP-LAI (RR: 1.81; 95% CrI: 0.97-3.55) and buprenorphine implant (RR: 2.28; 95% CrI: 0.98-5.38). Treatment discontinuation rates were similar between OUD treatments. Safety outcomes were generally comparable across treatments. Health-related quality of life indicated better recovery among patients treated with BUP-XR.

Conclusion: BUP-XR may enhance treatment retention and abstinence over other OUD therapies, supporting its integration into clinical pathways. The results may help guide future updates to OUD treatment guidelines and policies aimed at optimizing the use of long-acting formulations. Additional research is needed to better define the comparative effectiveness of LAIs.

To read the full text of the article, please visit the publisher’s website.

Journal: Journal of Neurophysiology, 2026, doi: 10.1152/jn.00504.2025

Authors: Eugene A. Kiyatkin, Feonil G. Limiac, Michael R. Noya, Juan L. Gomez, Michael Michaelides, & Yavin Shaham

Abstract:

Naloxone is the prototypical opioid receptor antagonist, whereas naloxone-methiodide, a quaternary naloxone analog, is widely used as a peripherally restricted antagonist based on the assumption that it does not cross the blood-brain barrier. This assumption has been central to arguments that peripheral opioid receptors contribute to fentanyl-induced respiratory depression. However, mass spectrometry studies show that although naloxone-methiodide has very limited permeability, it is detectable in brain tissue at an ∼1:50 concentration ratio compared with naloxone. Even such small amounts may be sufficient to act on brain receptors, raising the possibility of central involvement. To test this hypothesis, we used oxygen sensors coupled with amperometry in freely moving rats to examine the roles of central versus peripheral opioid receptors in fentanyl-induced brain hypoxia. We compared naloxone with naloxone-methiodide on oxygen responses in the brain and subcutaneous space following intravenous fentanyl administration (30 µg/kg). Naloxone-methiodide at a dose of 2.0 mg/kg (but not 0.2 mg/kg) blocked fentanyl-induced hypoxia. Naloxone-methiodide’s effect was weaker and shorter than that produced by 0.2 mg/kg naloxone. In addition, naloxone at doses 50- and 250-times lower (0.04 and 0.008 mg/kg), but not 1,000-times lower (0.002 mg/kg), also blocked fentanyl-induced hypoxia, mimicking the effect of 2.0 mg/kg naloxone-methiodide. These findings suggest that naloxone-methiodide is not a strictly peripheral antagonist. At moderate to high doses, naloxone-methiodide’s ability to reverse fentanyl-induced hypoxia may be partially mediated by the drug’s action on central opioid receptors.

NEW & NOTEWORTHY It is widely believed that opioids cause brain hypoxia through direct central nervous system action. This was challenged using naloxone-methiodide, which is believed to not cross the blood-brain barrier. However, mass-spectrometry data show limited brain entry, sufficient to block fentanyl-induced hypoxia. Our data reveal that naloxone is effective at 40 and 8 μg/kg doses, whereas naloxone-methiodide is not selective for peripheral opioid receptors. Its effects at higher doses arise mainly from central opioid receptor blockade.

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Journal: Journal of Racial and Ethnic Health Disparities, 2026, doi: 10.1007/ s40615-025-02830-x

Authors: Sunday Azagba, Todd Ebling, & Galappaththige S. R. de Silva

Abstract:

Introduction: Alcohol, cannabis, and e-cigarettes are among the most commonly used substances among U.S. high school students. This study examines the associations between the intersection of school belonging, perceived racial mistreatment, and substance use.

Methods: Data were drawn from the 2023 Youth Risk Behavior Survey of high school students. An analysis was conducted using a novel composite measure combining school belonging (closeness to people at school) and perceived racial mistreatment (unfair treatment due to race/ethnicity). Multivariable logistic regression analyses, adjusted for demographics and sexual identity, examined associations between the composite score and past 30-day use of alcohol, cannabis, and e-cigarettes.

Results: Higher composite scores, indicating more school belonging and lower perceived racial mistreatment, were associated with lower odds of using alcohol (OR = 0.93, 95% CI = 0.88–0.99), cannabis (OR = 0.87, 95% CI = 0.83–0.92), and e-cigarette (OR = 0.87, 95% CI = 0.82–0.91). Sex-stratified analyses revealed that higher composite scores were significantly associated with protective odds for females across all substances (alcohol, OR = 0.91, 95% CI = 0.85–0.97; cannabis, OR = 0.87, 95% CI = 0.81–0.94; and e-cigarette, OR = 0.86, 95% CI = 0.81–0.92). For males, significant protective associations were observed for cannabis and e-cigarette use, though the association for alcohol use was not statistically significant.

Conclusion: The findings suggest that greater school belonging and lower racial mistreatment are associated with lower odds of substance use among adolescents. Efforts to improve school climate and reduce racial mistreatment may be beneficial.

To read the full text of the article, please visit the publisher’s website.