Friends Research Institute

In 2018, the National Institutes of Health (NIH) launched the Helping to End Addiction Long-Term ® (HEAL) Initiative to advance addiction and pain research and clinical practice. The NIH-HEAL Initiative supports investigator-initiated research across diverse focus areas, allowing scientists discretion in selecting research topics, methodologies, and outcomes while still remaining subject to NIH's peer review process. This study aims to answer the research question: what do investigators of NIH-HEAL funded studies define as important knowledge, particularly in relation to growth in empirical studies and clinical policy? By examining how pain and addiction researchers define what knowledge is important to produce, this study offers novel insight into how research priorities take shape and why this matters for science and clinical practice. To answer this research question, we conducted a directed content analysis of 1,068 NIH-HEAL funded study abstracts published on the NIH RePORTER website. Our findings suggest that while the scope of the NIH-HEAL funded studies is broad, there are common identifiable patterns that exist within the funded research portfolio such as a preference for treating pain and addiction conditions with prescription medication (33.80% of pain studies, 34.17% of opioid use disorder studies) and a narrow focus on intervention efficacy (43.21% of pain studies, 39.22% of opioid use disorder studies). This analysis is important for the scientific enterprise and clinical practice as prior literature has painted research as inherently influenced by the values of a scientist and of their discipline. By identifying what social and empirical problems NIH-HEAL funded investigators identify, their proposed solutions, and the outcomes they prioritize, this study carries important implications for grant-funding agencies, scientists, and the people who need and receive treatment for pain and addiction conditions.

Human milk is critical for maternal-infant health, yet concerns about cannabis exposure through milk may discourage breastfeeding. We examined the relationship between breastfeeding and developmental outcomes among infants with prenatal cannabis exposure. We used a regional perinatal data repository from an academic hospital system with universal maternal urine drug testing. Breastfeeding status was obtained from birth certificates. Developmental delay was identified through ICD-9/10 billing codes for delayed milestones or speech disorders. Infants whose mother tested positive for cannabis at delivery were included. Descriptive statistics compared demographic characteristics by breastfeeding status, and logistic regression estimated the odds of developmental delay. Among 1,520 infants born from 2013 to 2019 with a maternal positive drug test for cannabis at delivery, 818 (54%) were not breastfed, and 702 (46%) were breastfed. In unadjusted analysis, not breastfeeding was associated with increased odds of developmental delay (OR: 1.32, 95% CI: 1.00-1.76). After adjusting for maternal tobacco use, prematurity, and birth year, this association was no longer statistically significant (OR: 1.24, 95% CI: 0.93-1.67). In this study, developmental outcomes did not differ by breastfeeding status among infants with prenatal cannabis exposure. These findings support current guidance from professional organizations that cannabis use is not a contradiction to breastfeeding. Further research with larger sample sizes and detailed longitudinal data is needed to better assess the potential protective role of breastfeeding against developmental delay and safety in the context of maternal cannabis use.

ObjectiveMaternal morbidity and mortality (MMM) rates from drug overdoses have increased, especially among pregnant and postpartum women aged 35–44. However, there is limited understanding of how current toxicology testing practices are implemented in hospital settings and how well they support, or undermine, linkage to care. The goal of the study is to understand variations in toxicology testing use among pregnant and postpartum women, explore hospital- and individual-level differences, and assess outcomes.MethodsUsing the Socio-cultural Framework for the Study of Health Service Disparities (SCF-HSD) we will perform a mixed-methods study to understand testing policies and practices in NY State.Aim 1 will employ multilevel statistical models using New York State Medicaid claims data (2021–2024) to identify predictors of perinatal toxicology testing and characterize hospital-level variation across hospitals. Aim 2 will involve one-on-one interviews with hospital administrators and clinical staff to document and analyze testing policies and practices, capturing diverse perspectives on testing rationales, attitudes, and adherence. Aim 3 will integrate quantitative and qualitative evidence through a mixed-methods design, incorporating perspectives of individuals with lived experience, via focus group sessions to inform and refine hospital policy recommendations.DiscussionOur findings will inform how to improve disparities in toxicology testing for pregnant and postpartum women. Addressing these challenges requires shifting emphasis toward standardized, evidence-based toxicology testing protocols, strengthening pathways to supportive services, and advancing policy reforms that reduce stigma and inequities in care.

Maternal morbidity and mortality (MMM) rates from drug overdoses have increased, especially among pregnant and postpartum women aged 35-44. However, there is limited understanding of how current toxicology testing practices are implemented in hospital settings and how well they support, or undermine, linkage to care. The goal of the study is to understand variations in toxicology testing use among pregnant and postpartum women, explore hospital- and individual-level differences, and assess outcomes. Using the Socio-cultural Framework for the Study of Health Service Disparities (SCF-HSD) we will perform a mixed-methods study to understand testing policies and practices in NY State. Aim 1 will employ multilevel statistical models using New York State Medicaid claims data (2021-2024) to identify predictors of perinatal toxicology testing and characterize hospital-level variation across hospitals. Aim 2 will involve one-on-one interviews with hospital administrators and clinical staff to document and analyze testing policies and practices, capturing diverse perspectives on testing rationales, attitudes, and adherence. Aim 3 will integrate quantitative and qualitative evidence through a mixed-methods design, incorporating perspectives of individuals with lived experience, via focus group sessions to inform and refine hospital policy recommendations. Our findings will inform how to improve disparities in toxicology testing for pregnant and postpartum women. Addressing these challenges requires shifting emphasis toward standardized, evidence-based toxicology testing protocols, strengthening pathways to supportive services, and advancing policy reforms that reduce stigma and inequities in care.

Medetomidine, a veterinary α2-adrenergic agonist, has recently emerged as an adulterant in the non-medical opioid supply, yet human exposure has remained poorly characterized. We conducted a pragmatic retrospective cohort analysis utilizing chart review and liquid chromatography–tandem mass spectrometry (LC-MS/MS) toxicology testing on available urine samples from patients presenting to two hospitals in Philadelphia, PA, who fit two clinical phenotypes, intoxication or withdrawal. Samples also underwent glucuronidase pre-treatment to assess impact on the yield of medetomidine and xylazine metabolite detection. Testing identified universal exposure to medetomidine (58/58 samples) via the 3-hydroxy-medetomidine (3-OH-M) metabolite, post glucuronidase treatment and variable xylazine exposure (40/58 samples). Importantly, 32% of medetomidine exposures would have been missed without enzymatic pre-treatment. Patients exhibited two distinct clinical phenotypes: intoxication, characterized primarily by sedation; bradycardia; and often hypotension, and withdrawal, presenting with life-threatening tachycardia; hypertension and often encephalopathy. Notably, clinical phenotype correlated with urinary concentrations of 3-OH-M but not xylazine. These findings underscore the critical need for heightened clinical awareness and need for contemporaneous toxicologic screening mechanisms for medetomidine exposure, emphasizing its distinct clinical presentations and the potential public health implications posed by its widespread adulteration in illicit opioids.

Background The culturally responsive cognitive behavioral therapy mobile app, Getting Off, was developed to reduce methamphetamine use and improve sexual health among sexual minority men (SMM). Methods From May 2021 to May 2023, 226 SMM were enrolled and randomized into 1 of 2 conditions: Immediate Delivery (ID) of the Getting Off app or Delayed Delivery (DD) after a 30-day period. Participants in both conditions received the same app and were given 30 days to complete the 24 in-app sessions. Analyses described in-app session utilization/engagement/completion and identified factors associated with session utilization/engagement/completion. Results App utilization was non-normally distributed, with most participants either accessing/completing zero sessions, 1–6 sessions, or all 24 sessions. Participants in the ID condition accessed and completed significantly more sessions than those in the DD condition. Participants reporting higher education, higher annual income, and an STI in the past 12 months utilized and completed more sessions. Adjusting for covariates and randomization group, participants facing unstable housing were less likely to access any sessions (OR = 0.44, p = 0.0393), while those with polysubstance use in the past 12 months were more likely to access at least one session (OR = 4.87, p = 0.0003). Those making higher than $60,000 annual income had higher odds of completing all 24 sessions than those making $15,000 or below (OR = 4.81; p = 0.0148). Conclusions Social determinants of health, such as unstable housing, can hinder utilization and engagement in app-based behavioral interventions. Additional health challenges, such as polysubstance use, may enhance engagement in app sessions.

Background/Objectives: Philadelphia has experienced a surge in illicit fentanyl adulterated with alpha-2 agonist sedatives. Initially, xylazine (“tranq”) was the predominant adulterant, and a novel multimodal withdrawal protocol was effective at mitigating symptoms. However, since mid-2024, medetomidine—a more potent sedative—has largely supplanted xylazine. Clinicians have reported more severe, treatment-resistant opioid withdrawal during this transition. To assess whether a previously effective withdrawal management protocol retained efficacy after the emergence of medetomidine as the primary fentanyl adulterant in a community. Methods: We conducted a retrospective cohort study of patients receiving protocol-based opioid withdrawal treatment at two emergency departments in Philadelphia between September 2022 and April 2025. Patients were divided into the xylazine era (September 2022–July 2024) and medetomidine era (August 2024–April 2025). The primary outcome was a change in Clinical Opioid Withdrawal Scale (COWS) score from pre- to post-treatment. Secondary outcomes included rates of discharge against medical advice (AMA) and ICU admission, as well as the impact of a revised treatment protocol. Results: Among 1269 encounters with full data, 616 occurred during the xylazine era and 770 during the medetomidine era. Median COWS reduction was greater in the xylazine group (−9.0 vs. −4.0 points, p < 0.001), with more patients achieving symptom relief (COWS ≤ 4: 65.6% vs. 14.2%, p < 0.001). ICU admission occurred in 8.5% of xylazine era patients and 16.8% of medetomidine era patients (p < 0.001). Rates of AMA were higher during the medetomidine era as well (6.5% vs. 3.6%) (p = 0.038). Revision of treatment protocols showed promise. Conclusions: The protocol was significantly less effective during the medetomidine era, though a protocol change may be helping. Findings highlight the need to adapt withdrawal treatment protocols in response to changes in the illicit drug supply.

In this viewpoint, we explore the use of big data analytics and artificial intelligence (AI) and discuss important challenges to their ethical, effective, and equitable use within opioid use disorder (OUD) treatment settings. Applying our collective experiences as OUD policy and treatment experts, we discuss 8 key challenges that OUD treatment services must contend with to make the most of these rapidly evolving technologies: data and algorithmic transparency, clinical validation, new practitioner-technology interfaces, capturing data relevant to improving patient care, understanding and responding to algorithmic outputs, obtaining informed patient consent, navigating mistrust, and addressing digital exclusion and bias. Through this paper, we hope to critically engage clinicians and policy makers on important ethical considerations, clinical implications, and implementation challenges involved in big data analytics and AI deployment in OUD treatment settings.

People experiencing homelessness (PEH) face a high risk of opioid-related deaths, yet there is limited qualitative data on the barriers encountered when accessing buprenorphine treatment for opioid use disorder (OUD). To address this gap, we interviewed 28 clinicians, outreach workers, and administrators from organizations serving PEH with OUD. Our goal was to understand the barriers and facilitators at the patient, clinic, and institutional levels and gather recommendations for improvement. Interviews, conducted via Zoom and analyzed through thematic analysis, revealed several barriers. At the patient level, themes related to barriers included knowledge and experience (e.g., limited knowledge about buprenorphine options; rejection of buprenorphine due to prior experience with precipitated withdrawal); concerns about the medication and its administration (e.g., distrust of injectable medications; concerns about treatment control, and a prolonged informed consent process for extended-release injectable buprenorphine); and challenges due to homelessness (e.g., identification requirement to access medication at pharmacies, difficulties managing buprenorphine while unsheltered). At the clinic level, themes centered around staffing (e.g., lack of training and experience in treating PEH and staffing shortages) and health care-related stigma (e.g., discriminatory attitudes toward PEH with OUD). Institutional-level themes included state-regulatory factors (e.g., practice regulations limiting clinical pharmacists’ ability to prescribe buprenorphine) and access factors (e.g., stigmatization of buprenorphine prescribing, limited low-barrier buprenorphine access, and care system complexity). Recommendations included educational programs for patients and clinicians to increase understanding and reduce stigma, integrating buprenorphine treatment into non-traditional settings, and providing housing with treatment.

The primary objective of this study is to conduct a systematic review of the scientific literature on the practice of methadone split-dosing, where the total daily dose is divided into 2 or more doses taken 10-12 hours apart rather than administered as a single daily dose. The review aims to evaluate the perinatal effects of this dosing regimen on maternal, fetal, and neonatal outcomes. A systematic review was conducted by searching 6 databases, including APA PsycInfo, the Cochrane Library, CINAHL, Embase, PubMed, and Scopus, through the last search date of June 13, 2023. We included studies that reported maternal, fetal, or neonatal outcomes. Multiple researchers screened references. Data were extracted using a standardized spreadsheet, including study details and outcomes, and included studies were assessed for bias independently by 2 researchers using JBI Critical Appraisal Tools. The systematic search yielded 612 unique references, of which 8 studies met the criteria. These studies focused on investigating the pharmacokinetics of methadone during pregnancy, fetal responses to maternal methadone administration, variables related to maternal substance use disorder treatment, and outcomes related to birth or neonatal health. The findings demonstrated significant alterations in methadone metabolism during pregnancy due to increased methadone metabolism as a result of enhanced hepatic enzyme activity (CYP3A4 and CYP2B6), resulting in lower plasma methadone levels and requiring dose adjustments. Neonatal outcomes were favorable, including higher birth weights, reduced preterm birth risk, improved intrauterine growth, and reduced neonatal abstinence syndrome (NAS). The evidence suggests that pregnancy significantly alters methadone metabolism, subsequently impacting both maternal and neonatal outcomes. These findings demonstrate that split-dosing of methadone is associated with more favorable outcomes compared with once-daily dosing.