Open research questions in Opioid Use Disorder Treatment

What the literature leaves open

• Additionally, given the limited data identified and the legal and medical risks associated with OUD, further consideration of safety and privacy is warranted.

  Digital mental health tools for use by individuals in opioid use recovery: An academic scoping and commercial review · 2026 · DOI

• While prior literature has consistently demonstrated a positive relationship between ACSs and MOUD initiation, there have been mixed results on the relationship with read- missions and length-of-stay.

  Association Between Hospital-Based Addiction Consult Service Implementation and Hospital Length-of-Stay and 30-Day Readmission Rates for Patients with Opioid Use Disorder · 2026 · DOI

• , 2007, Krupitsky & Blokhina, 2010), this study affirms that non-compliance may not be limited to the oral preparation of these medications, as previously suggested. This falls in line with the mixed findings from prior research on MOUD and mortal- ity, which demonstrates a clearer relationship between MOUD and non-fatal health events such as overdoses (see Strange et al.

  The effects of offering treatment with injectable naltrexone during reentry on long-term mortality · 2026 · DOI

• The current study has several important limitations, and the results should be considered with them in mind. These include a relatively small sample size (n = 94), which has implications for statistical power, and a low degree of treatment 1 3The effects of offering treatment with injectable naltrexone during… compliance. Additionally, there are divergences within the demographics of the pilot study population and the complete standing carceral population. For example, the pilot had a meaningful overrepresentation of female individuals (i.e., 40% of the study participants were identified as female, though only about 6% of the carceral population was similarly identified at that time) due to the nature of the participating facilities. A reliance on agency administrative records limits the scope of data available; any individual in the study could have sought other treatment options, including but not limited to MOUD. Though balanced within the research design, outcome data are restricted to mortality in Pennsylvania and so do not reflect the prevalence of events that took place outside of this jurisdiction or where the identity of the deceased individual was not recorded. Temporal and geographic variations in the opioid crisis, particularly as they relate to levels of fentanyl penetration and the resultant impact on overdose risk during the study period (2015–2017), are not cap- tured here but represent an important consideration for future research that employs larger and more temporally and geographically variable samples. Concerning health and mortality, the currently available data do not include records of non-fatal overdoses and other, drug-related harms that did not result in death. These are key outcomes and should be explored to better understand the impact.

  The effects of offering treatment with injectable naltrexone during reentry on long-term mortality · 2026 · DOI

• Importance Although US opioid overdose deaths have recently declined, mortality remains higher than before the COVID-19 pandemic, and the role of naloxone in opioid-associated out-of-hospital cardiac arrest (OA-OHCA) remains uncertain.

  Naloxone and Clinical Outcomes in Suspected Opioid-Associated Out-of-Hospital Cardiac Arrests · 2026 · DOI

• Importance: Due to the impact of high-potency synthetic opioids on medication for opioid use disorder (MOUD) initiation, hospital-based addiction clinicians adapted their practice to improve care, with decisions often guided by limited evidence.

  Best Practices for Hospital-Based Initiation of Medications for Opioid Use Disorder · 2026 · DOI

• Because validated screening tools for suicide risk are insufficient for detecting intentional opioid overdose risk, a screening tool developed specifically for this purpose using validated psychometric methods is necessary to identify and intervene in the morbidity and mortality associated with intentional opioid overdose.

  Detecting Suicidality in Opioid Use Disorder Requires an Understanding of Intentional Opioid Overdose · 2026 · DOI

• While opioid injection is a major risk factor for IE, the risk associated with specific prescription opioids, such as hydromorphone, remains unclear and is inconsistently reported, despite a hypothesized pathway whereby the insolubility of controlled-releaseformulations may promote injection equipment reuse and bacterial contamination.

  Recent hydromorphone injection and risk of incident infective endocarditis among people who inject drugs in Toronto, Canada: a cohort study · 2026 · DOI

• This evaluation focused on publicly available dashboards and emphasized opioid-related mortality. It did not include dashboards centered on nonfatal overdose, prescribing, or clinical outcomes. Some states group opioid data with broader substance use measures, which limits direct com- parison. Some states may report data at broader geographic or temporal resolutions not due to limited dashboard capa- bilities, but due to privacy regulations and data suppression policies. The framework assigns equal weight to all features, which may not reflect their relative importance for specific users. While the framework demonstrated reasonable inter- rater consistency through dual review by both authors and a single external reviewer, further testing across additional reviewers would strengthen confidence in its reproducibil- ity. Even with these limits, the framework offers a clear and Page 5 of 6 85 reusable starting point for future refinement and use across public health surveillance systems.

  A Standardized Framework for Evaluating State Opioid Surveillance Dashboards: A Health Informatics Assessment · 2026 · DOI

• This study is among the first to apply SNA to opioid-related discourse on Twitter/X, and one of its key contributions is the discovery of emerging dynamics that set it apart from earlier research. Contrary to the previous studies, our results indicate that AI accounts are increasingly becoming active contributors to opioid discussions. By documenting this transformation and spotlighting the rise of AI-driven accounts, the analysis underscores the dynamic evolution of social media content. This finding enhances our understanding of communication patterns and shows new opportunities for integrating AI with healthcare professionals. The dominance of AI in opioid discussions is significant, leading to two key implications. First, http://z.umn.edu/INNOVATIONS 2026, Vol. 17, No.

  Innovating opioid research with social media data: A social network analysis of Twitter conversations · 2026 · DOI

• This study has limitations. Time-varying factors not accounted for in our study may have influenced the study outcomes, such as evolving harm reduction initiatives. As CPSBC released a policy allowing wider prescribing of buprenorphine/naloxone shortly after introducing pre- scribing standards related to opioid analgesics, this may have affected some of our findings regarding the prescribing standards. To account for this, we have considered both policies in our interpretation when rele- vant. As our definitions of rapid vs gradual tapering and discontinuation may have affected our results, we conducted sensitivity analyses varying our outcome definitions to help the reader consider to what extent our findings related to definitions used. Our findings may also have been affected by the interrelation of study outcomes, which was not accounted for in our study design. For example, in cases where a policy was associated with a short-term increase in rapid discontinuation, this might have influenced other study outcomes such as the frequency of longer-term gradual discontinuation. The administrative health data used in our study included information in prescription drug dispensa- tions, but this may differ from patients’ actual use of prescription drugs and we lacked information about use of unregulated drugs. In addition, it was unclear whether changes in tapering and discontinuation re- flected changes in prescriber or patient responses to policies and events or shared decision-making. While we analyzed cohorts by OUD and OAT status, we did not investigate whether policy impacts differed for sub- groups defined by demographic or other patient characteristics. Future research could investigate whether other groups were disproportion- ately affected by impacts of these or similar policies and events on opioid tapering and discontinuation.

  Impact of health policies on opioid tapering and discontinuation among patients receiving long-term opioid therapy for chronic noncancer pain · 2026 · DOI

• The subjective group who underwent toxicology tests may also change over the years, which may lead to biased proportions, as not all ED admissions were screened for toxicology. Another limitation is that physician deci- sions for toxicology screening may include other non- opioid substances as well, influencing results. The trend of other substances is not part of the current manuscript. However, benzodiazepines were reduced, and cannabis increased during the “fentanyl-tested” 2023–2024 period compared with the earlier period 2019–2022. Another limitation is the small duration of the follow-up since the introduction of the fentanyl test in the ED. The regula- tions published regarding opioid prescriptions, which particularly restrict fentanyl, parallel to the fentanyl screening in ED, may change the opioid increase trend in ED, and it is unknown how it would affect users. Another limitation is that while the studied ED is a large tertiary medical center in the biggest municipal city in Israel, treating diverse populations, this is still only a single hos- pital study, which may have limited relevance for other EDs throughout the country. Another limitation is the possibility that naloxone was administered empirically in some cases that weren’t opioid-related. Lastly, the analy- sis is based on de-identified electronic data, with the lim- itation of no possibility to be sure that all patients tested were included.

  The positivity rate of opioid drug urine testing in an emergency department between 2016 and 2024, before and after the introduction of fentanyl testing · 2026 · DOI

• This study is further limited by a small sample size and lack of a contemporary control group to evaluate how the LDI protocol compares directly to a traditional induc- tion strategy, although data from our SSP indicate a 59% 3-month retention rate on buprenorphine [14].

  Implementation of low-dose buprenorphine induction at a syringe services program · 2026 · DOI

• The study aims to establish an annual session to reinforce resident confidence and increase clinical utilization of POCUS for pediatric head trauma, but effectiveness of repeated training interventions has not been evaluated.

  An Addiction Medicine Program for Emergency Medicine Residents · 2025 · DOI

• Using data from Proyecto SALTO, a 15-year follow-up study of a cohort of Mexican American women in a low-income community in San Antonio, Texas, this study examines emerging patterns of current methamphetamine (MA) use, including opioid co-use, among this understudied population.

  Correlates of Current Methamphetamine Use and Opioid Co-Use Among Latina Women in a Low-Income Community · 2024 · DOI

• Importance: Previous studies on the comparative effectiveness between buprenorphine and methadone provided limited evidence on differences in treatment effects across key subgroups and were drawn from populations who use primarily heroin or prescription opioids, although fentanyl use is increasing across North America.

  Buprenorphine/Naloxone vs Methadone for the Treatment of Opioid Use Disorder · 2024 · DOI

• <h3>Interpretation:</h3> Although additional research is needed, this preliminary evidence indicates that SOS programs can play an important role in the expansion of treatment and harm-reduction options available to assist people who use drugs and who are at high risk of drug poisoning.

  Clinical outcomes and health care costs among people entering a safer opioid supply program in Ontario · 2022 · DOI

• Introduction: Although a substantial body of research documents a relationship between traumatic stress in childhood and the initiation of substance use later in the life course, only limited research has examined potential linkages between adverse childhood experiences (ACEs) and the initiation of non-medical prescription opioid use and other opioid use behaviors.

  Adverse Childhood Experiences Predict Early Initiation of Opioid Use Behaviors · 2021 · DOI

• The rates of such multimorbidities are likely to vary between men and women with OUD and may have important implications for treatment within the VHA but have not yet been studied.

  Sex Differences in Opioid Use Disorder Prevalence and Multimorbidity Nationally in the Veterans Health Administration · 2021 · DOI

• Based on the mechanism of action of low-doses of naltrexone, which is not fully known, researchers are trying to confirm reports concerning the efficacy and safety of the therapy in many diseases, including autoimmune disorders (including Crohn's disease, multiple sclerosis), fibromyalgia and chronic pain, cancer or dermatological diseases.

  Low Dose Naltrexone - Efficacy and safety of off-label use therapy. · 2020 · DOI

• This study attempts to fill this gap in the literature by assessing provider-based stigma toward opioid-using persons among a sample of 208 police officers working for departments located in the Northeastern Region of the United States.

  Police officers, stigma, and the opioid epidemic · 2020 · DOI

• Although systematic patterns of geographic variation in OUD and opioid overdose have been identified, the factors that explain why opioid-related hospitalizations increase in certain areas are not well understood.

  Investigating the Social Ecological Contexts of Opioid Use Disorder and Poisoning Hospitalizations in Pennsylvania · 2018 · DOI

• Whereas American Indians/Alaska Natives (AI/AN) have experienced larger increases in drug overdose mortality than have other racial/ethnic groups in the United States (2), little is known about the regional impact of opioids in tribal and urban AI/AN communities.

  Drug, Opioid-Involved, and Heroin-Involved Overdose Deaths Among American Indians and Alaska Natives — Washington, 1999–2015 · 2018 · DOI

• BACKGROUND: Research has demonstrated that patients with opioid use disorders (OUD; including both opioid abuse and/or dependence) have poorer neuropsychological functioning compared to healthy controls; however, the pattern and robustness of the findings remain unknown.

  Neuropsychological functioning in opioid use disorder: A research synthesis and meta-analysis · 2018 · DOI

• While buprenorphine and naltrexone are both used for adolescents and young adults with opioid use disorder (OUD), the extent of such use has not been studied on a national basis, until the publication in JAMA Pediatrics in July of a study by Scott E.

  Only 1 in 4 teens/young adults with OUDs get naltrexone or buprenorphine: Study · 2017 · DOI

Most-cited papers in Opioid Use Disorder Treatment

• Drug and Opioid-Involved Overdose Deaths — United States, 2017–2018 · MMWR Morbidity and Mortality Weekly Report · 2020 · 984 citations
• Trends and Geographic Patterns in Drug and Synthetic Opioid Overdose Deaths — United States, 2013–2019 · MMWR Morbidity and Mortality Weekly Report · 2021 · 944 citations
• Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use — United States, 2006–2015 · MMWR Morbidity and Mortality Weekly Report · 2017 · 843 citations
• Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain · JAMA · 2018 · 796 citations
• Opioid Dose and Drug-Related Mortality in Patients With Nonmalignant Pain · Archives of Internal Medicine · 2011 · 467 citations
• The economic burden of opioid use disorder and fatal opioid overdose in the United States, 2017 · Drug and Alcohol Dependence · 2020 · 449 citations
• Persistent Opioid Use Among Pediatric Patients After Surgery · PEDIATRICS · 2017 · 401 citations
• Signal of increased opioid overdose during COVID-19 from emergency medical services data · Drug and Alcohol Dependence · 2020 · 367 citations
• Association Between Mental Health Disorders, Problem Drug Use, and Regular Prescription Opioid Use · Archives of Internal Medicine · 2006 · 360 citations
• A Single-Question Screening Test for Drug Use in Primary Care · Archives of Internal Medicine · 2010 · 354 citations

Most recent work

• Detecting Suicidality in Opioid Use Disorder Requires an Understanding of Intentional Opioid Overdose · Journal of Addiction Medicine · 2026
• Does 6.7% Reflect Reality? Response to “Precipitated Withdrawal Following Emergency Department-initiated Buprenorphine: A Retrospective Study” · Journal of Addiction Medicine · 2026
• Best Practices for Hospital-Based Initiation of Medications for Opioid Use Disorder · JAMA Network Open · 2026
• Naloxone and Clinical Outcomes in Suspected Opioid-Associated Out-of-Hospital Cardiac Arrests · JAMA Network Open · 2026
• Treatment Initiation and Retention Among Medicaid Enrollees Diagnosed With Opioid Use Disorder in South Carolina · Journal of Addiction Medicine · 2026
• Too Many Pills, Too Little Attention: Emphasizing Psychotropic Polypharmacy in the Overdose Conversation · Journal of Addiction Medicine · 2026
• Postpartum Buprenorphine: A Descriptive Analysis of Dose Adjustments and Treatment Retention · Journal of Addiction Medicine · 2026
• The positivity rate of opioid drug urine testing in an emergency department between 2016 and 2024, before and after the introduction of fentanyl testing · Substance Abuse Treatment, Prevention, and Policy · 2026
• Implementation of low-dose buprenorphine induction at a syringe services program · Addiction Science & Clinical Practice · 2026
• Amputation Rates Among Opioid-Related Hospitalizations in the United States, 2016 to 2022 · Annals of Internal Medicine · 2026

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