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Introduction: The initiation of buprenorphine for patients with opioid use disorder (OUD) in the emergency department (ED) has been associated with improved outcomes including reduced ED visits and increased treatment engagement. Though both standard-dose (8 mg buprenorphine equivalent) and high-dose (24 mg buprenorphine equivalent) strategies to initiate buprenorphine have been used in the ED, no prospective trials comparing outcomes among patients receiving these treatments have been reported.

Methods and analysis: This multisite randomised clinical trial (CTN-0145) is a multisite double-blind, double-dummy, randomised clinical trial enrolling 360 emergency department patients with moderate-to-severe OUD. Enrolled patients will be randomised to one of two study arms: standard-dose induction or high-dose induction, both provided in the ED. This study will engage, train and provide resources to five EDs throughout the US to recruit patients with untreated OUD into a randomised clinical trial. The primary aim is to evaluate the effects of the standard-dose induction and high-dose induction on rates of OUD treatment participation within 10 days post-randomisation. The secondary aims are to evaluate differences between standard-dose induction and high-dose induction on the outcomes of opioid craving, opioid withdrawal symptoms and illicit drug use assessed during 10 days post randomisation and evaluate the effects between treatment arms on rates of OUD treatment participation within 30 days post randomisation.

Ethics and dissemination: This study is funded by the National Institute on Drug Abuse and has been approved by the WCG Instutitional Review Board. It has been registered at clinicaltrials.gov. This study will inform the strategy for treatment initiation with buprenorphine among diverse ED settings and will provide ongoing evidence to support the safety and efficacy of initiating treatment for OUD in the ED.

Related protocols: CTN-0145

Purpose: Emergency Departments (ED) are important settings for initiating care following a non-fatal opioid overdose (NFOO). While ED-based interventions, including peer-led recovery support and initiation of medications for opioid use disorder (MOUD), are promising methods for reducing subsequent overdoses and mortality, randomized trials of ED-based overdose prevention or treatment- linkage interventions demonstrate that a substantial proportion of patients decline participation. The current secondary analysis is designed to characterize individuals who declined to participate in one such study.

Methods: Data were used from the Peer Intervention to Link Overdose Survivors to Treatment (PILOT) trial (CTN-0107), which was a multi-site study conducted in three US-based EDs that randomized participants to a 6-month peer-led overdose prevention intervention or treatment as usual in the ED. Demographics and clinical characteristics of those enrolled in PILOT (n = 150) were compared to those who declined to participate but completed a screening exit survey (ScrES; n = 46).

Results: Among those who declined study participation, 76% had experienced a prior overdose preceding the current overdose that brought them into the ED (58.7% within the past 72 h), 56.5% were not currently engaged in substance use treatment and among those, 65.4% expressed a desire for treatment. Odds of declining study participation decreased with age by 6% per year (OR = 0.94, 95% CI: 0.9, 0.99); those with any college experience had odds of declining at 3 times greater than those without a high school diploma (OR = 3.4, 95% CI: 1.2, 10.1). Those without health insurance had odds of declining nearly 3 times those with insurance (OR = 2.9, 95% CI: 1.2, 7.0). Frequently cited reasons for declining were a desire to leave the ED or feeling unwell (39.1%), lack of interest in research (30.4%) and a belief the intervention would not be helpful (17.4%).

Conclusions: Results from this analysis characterize ED patients declining to participate in peer-led overdose prevention research with the goals of enhancing future recruitment strategies and enrolling more representative samples to reduce subsequent overdoses. Future work is needed to determine how to better engage priority populations at critical touch points, while ensuring that interventions are flexible, patient-centered, and potentially offer remote access.

Related protocols: CTN-0107

This editorial in JAMA describes the outcomes and implications of the primary outcomes paper for CTN-0099, the ED-INNOVATION trial, which compared the use of a 7-day extended-release buprenorphine injection to 7 days of sublingual buprenorphine for patients in the ED presenting with opioid use disorder and found no difference in treatment engagement at 7 days or 30 days among the two groups. They also reported low rates of precipitated withdrawal in both groups, despite a high rate of fentanyl use.

In the context of an ongoing public health emergency related to drug toxicity deaths, emergency department visits are undeniably important opportunities to identify people with high-risk opioid use and engage them in care. Increasing access to evidence-based harm reduction and treatment options for people with OUD in EDs is a crucial aspect of the response to this public health emergency.

Increasing the choices of opioid agonist therapies available in EDs is important. Providers should be careful to monitor their own biases regarding which approach might work best for an individual patient (for example, many providers might assume an injection is the easiest or best approach for a patient, while the patient may feel differently).

This study provides further evidence that EDs can and must lead ED-specific studies and initiatives that confirm best practices and increase access to lifesaving opioid agonist therapies. The way forward requires that clinician-scientists continue to foster a discussion of what is possible in EDs, while prioritizing patient-centered decision-making and consent, and clearly establishing both safety and benefit of interventions prior to implementation.

Related protocols: CTN-0099

This is the primary outcomes article for CTN-0099.

Importance: Extended-release injectable buprenorphine may expand the reach of initiating medications for opioid use disorder in high-risk and hard-to-reach individuals who visit the emergency department (ED) and can be administered in low levels of withdrawal.

Objective: To compare the effect of ED-initiated 7-day extended-release injectable buprenorphine vs sublingual buprenorphine on treatment engagement at 7 days.

Design, Setting, and Participants: Multicenter randomized clinical trial enrolling adult patients presenting to the ED with untreated opioid use disorder and a Clinical Opiate Withdrawal Scale (COWS) score of 4 or higher across 29 EDs in the US from July 12, 2020, to August 21, 2024. Final follow-up was completed on October 24, 2024.

Interventions: Patients were randomized to receive a 24-mg injection of extended-release buprenorphine (equivalent to 16 mg/d) or sublingual buprenorphine, which included either self-administration instructions if the COWS score was less than 8 or administration of 8 mg of sublingual buprenorphine in the ED if the COWS score was 8 or higher. All sublingual buprenorphine group patients received a 7-day prescription for 16 mg/d. Both groups were provided referral for ongoing medication with a scheduled appointment within 7 days.

Main Outcomes and Measures: Engagement in opioid use disorder treatment on day 7 was the primary outcome. Secondary outcomes included engagement at 30 days, precipitated withdrawal and overdose events, craving scores, days of illicit opioid use, and patient satisfaction with treatment.

Results: Among 2000 patients randomized, 6 who were enrolled twice were excluded, resulting in 991 in the extended-release group and 1003 in the sublingual group. The median age was 37 (IQR, 30-47) years, 68% were male, 31% had an initial COWS score of 4 to 7, and 76% tested positive for fentanyl. The adjusted proportion of engagement in opioid use disorder treatment at 7 days was 40.5% with extended-release buprenorphine vs 38.5% with sublingual buprenorphine (adjusted difference, 1.6%; 95% CI, −2.8% to 6.0%). Engagement at 30 days was similar, with adjusted proportions of 43.8% with extended-release buprenorphine vs 44.9% with sublingual buprenorphine (adjusted difference, −1.5%; 95% CI, −6.2% to 3.2%). Precipitated withdrawal was rare: 6 (0.6%) with extended-release buprenorphine and 8 (0.8%) with sublingual buprenorphine. Overdose events within 30 days occurred in 18 participants (2.3%) in each group. Patients receiving extended-release buprenorphine reported lower mean craving scores at 7 days vs those receiving sublingual buprenorphine (scale, 0-100; mean score, 26.5 vs 30.2, respectively; adjusted mean difference, −3.85; 95% CI, −7.08 to −0.63), fewer days of illicit opioid use in the past 7 days (adjusted ratio of means, 0.77; 95% CI, 0.68-0.95), and better treatment satisfaction scores (scale, 1-5; adjusted mean difference, 0.13; 95% CI, 0.01-0.25).

Conclusions and Relevance: No difference was detected in opioid use disorder treatment engagement on day 7 between the 7-day extended-release and sublingual buprenorphine groups. Both buprenorphine formulations were well tolerated; precipitated withdrawal was rare despite a high prevalence of fentanyl.

Related editorial: Moe J, et al. Buprenorphine in the ED — Balancing access, safety, and autonomy. JAMA 2026 (in press).

Related protocols: CTN-0099

Randomized clinical trials (RCTs) typically report patient-oriented outcomes. However, site engagement in RCTs requires substantial investment in personnel, training, and institutional resources, which may have lasting effects on personnel and institutional culture. Additionally, engagement in research has been associated with improved health care performance at the institutional level, including in prior studies at substance use treatment centers within the National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN). Nonetheless, little has been reported about downstream effects of site participation for emergency department (ED)-based studies, including investigator professional advancements and institution-wide improvements in clinical practice. This commentary piece describes individual- and site-level benefits associated with participation in the Emergency Department-Initiated Buprenorphine and Validation Network Trial (ED-INNOVATION, CTN-0099).

Related protocols: CTN-0099

Background: Adoption of ED-initiated buprenorphine for opioid use disorder has been slow despite evidence of its effectiveness. Implementation facilitation (IF) is an evidence-based implementation strategy to promote adoption of new practices within clinical settings. The Clinical Trials Network (CTN)-0069 Project ED Health” study evaluated whether provision of ED-initiated buprenorphine with referral for community-based medication for opioid use disorder (MOUD) increased after IF. We identified the health system resources required to conduct IF and sustain ED-initiated buprenorphine with referral for community-based MOUD and then calculated the financial costs associated with using those resources.

Methods: We estimated costs using nationally representative employee values of the formative evaluation and other IF-related resources (e.g., focus groups, clinician education, and academic detailing), using microcosting analysis to capture quantitative data and assign nationally-representative costs based on Drug Abuse Treatment Cost Analysis Program (DATCAP). The study data was collected from 2017 to 2020 from four sites. We calculated costs per site for three distinct phases: pre-implementation, IF, and sustainment.

Results: The mean, per-site, costs were: pre-implementation = $27,753 (range: $25,859$27,821), IF = $53,558 (range: $48,417-$59,468) and annual sustainment = $226,822(range: $104,871-$339,100), which resulted in a mean per-patient cost of $115 assuming an average of 195 patients identified with untreated OUD, per-month, across sites.

Conclusions: The microcosting analysis revealed the resources and costs involved in implementing ED-initiated buprenorphine programs at various sites. Understanding the different ways each site customized the IF strategy can improve adoption to this initiative. Interpreting the costs during the intervention and what it takes to sustain it will help decision makers address uncertainty and promote increased acceptance of implementing these practices in the context of potential benefits that this approach can provide.

Related protocols: CTN-0069

In this webinar for the CTN Translation & Implementation SIG, Gail D’Onofrio, MD, MS, and David A. Fiellin, MD, shared their study approach and results for CTN-0069: Opioid Use Disorder in the ED (Project ED Health), as well as considerations for integrating implementation outcome evaluations in efficacy/effectiveness protocols.

Study objective(s): To evaluate the cost-effectiveness of implementation facilitation compared with a standard educational strategy to promote emergency department (ED)-initiated buprenorphine with linkage to ongoing opioid use disorder care in the community, from a health care-sector perspective.

Methods: A prospective cost-effectiveness analysis was conducted alongside “Project ED Health” (CTN-0069), a hybrid type 3 implementation-effectiveness study conducted at 4 academic EDs. Resources were gathered and valued according to the health care-sector perspective. Three effectiveness measures were evaluated: quality-adjusted life-years, opioid-free years, and patient engagement in community-based opioid use disorder care on the 30th day following the index ED visit. An incremental cost-effectiveness ratio was calculated for each measure of effectiveness. Likelihood of cost-effectiveness was evaluated across a wide range of “value” thresholds through cost-effectiveness acceptability curves.

Results: The mean, per-person, health care-sector cost associated with ED-administered buprenorphine following implementation facilitation did not differ significantly from that of standard education ($3,239 versus $4,904), whereas the mean effectiveness for all 3 measures significantly favored the implementation facilitation strategy. Implementation facilitation has a 74% to 75% probability of being considered cost-effective from a health care-sector perspective at the recommended value range of $100,000 to $200,000 per quality-adjusted life-year. Incremental cost-effectiveness ratios estimated using secondary effectiveness measures had a 75% probability of being considered cost-effective at $25,000 per opioid-free year and $38,000 per engagement.

Conclusion: Implementation facilitation, relative to a standard educational strategy, has a moderate-to-high likelihood of being considered cost-effective from a health care-sector perspective, depending on decisionmakers’ willingness to pay for units of effectiveness.

Related protocols: CTN-0069

The increase in opioid-related overdoses has caused a decrease in average life expectancy, highlighting the need for effective interventions to reduce overdose risk and prevent subsequent overdoses. Peer support specialists (PSSs) offer an appealing strategy to engage overdose survivors and reduce overdose risk, but randomized controlled trials are needed to formalize peer-led interventions and evaluate their effectiveness.

Objective: This National Institute on Drug Abuse Clinical Trials Network (CTN) study is a multisite, prospective, pilot randomized (1:1) controlled trial (CTN protocol 0107) that aims to evaluate the effectiveness of an emergency department (ED)–initiated, peer-delivered intervention tailored for opioid overdose survivors (Peer Intervention to Link Overdose survivors to Treatment [PILOT]), compared with treatment as usual (TAU).

Methods: This study evaluates the effectiveness of the 6-month, PSS-led PILOT intervention compared with TAU on the primary outcome of reducing overdose risk behavior 6 months after enrollment. Adults (aged =18 years; N=150) with a recent opioid-related overdose were identified and approached in the ED. Participants were screened and enrolled, either in the ED or within 7 days of ED discharge at research offices or in the community and then asked to complete study visits at months 1, 3, 6 (end of intervention), and 7 (follow-up). Participants were enrolled at 3 study sites in the United States: Greenville, South Carolina; Youngstown, Ohio; and Everett, Washington. Participants randomized to the PILOT intervention received a 6-month, PSS-led intervention tailored to each participant’s goals to reduce their overdose risk behavior (eg, overdose harm reduction, housing, medical, and substance use treatment or recovery goals). Participants randomized to TAU received standard-of-care overdose materials, education, and services provided through the participating EDs. This paper describes the study protocol and procedures, explains the design and inclusion and exclusion decisions, and provides details of the peer-led PILOT intervention and supervision of PILOT PSSs.

Results: Study enrollment opened in December 2021 and was closed in July 2023. A total of 150 participants across 3 sites were enrolled in the study, meeting the proposed sample size for the trial. Primary and secondary analyses are underway and expected to be published in early 2025.

Conclusions: There is an urgent need to better understand the characteristics of overdose survivors presenting to the ED and for rigorous trials evaluating the effectiveness of PSS-led interventions on engaging overdose survivors and reducing overdose risk. Results from this pilot randomized controlled trial will provide a description of the characteristics of overdose survivors presenting to the ED; outline the implementation of PSS services research in ED settings, including PSS implementation of PSS supervision and activity tracking; and inform ED-initiated PSS-led overdose risk reduction interventions and future research to better understand the implementation and efficacy of these interventions.

Related protocols: CTN-0107

The US overdose epidemic is an escalating public health emergency, accounting for over 100,000 deaths annually. Despite the availability of medications for opioid use disorders, provider-level barriers, such as negative attitudes, exacerbate the treatment gap in clinical care settings. Assessing the prevalence and intensity of provider stigma, defined as the negative perceptions and behaviors that providers embody and enact toward patients with substance use disorders, across providers with different specialties, is critical to expanding the delivery of substance use treatment.

Objective: To thoroughly understand provider stigma toward patients with substance use disorders, we conducted a nationwide survey of emergency medicine and primary care physicians and dentists using a questionnaire designed to reveal how widely and intensely provider attitudes and stigma can impact these providers’ clinical practices in caring for their patients. The survey also queried providers’ stigma and clinical practices toward other chronic conditions, which can then be compared with their stigma and practices related to substance use disorders.

Methods: Our cross-sectional survey was mailed to a nationally representative sample of primary care physicians, emergency medicine physicians, and dentists (N=3011), obtained by American Medical Association and American Dental Association licensees based on specified selection criteria. We oversampled nonmetropolitan practice areas, given the potential differences in provider stigma and available resources in these regions compared with metropolitan areas. Data collection followed a recommended series of contacts with participants per the Dillman Total Design Method, with mixed-modality options offered (email, mail, fax, and phone). A gradually increasing compensation scale (maximum US$250) was implemented to recruit chronic nonresponders and assess the association between requiring higher incentives to participate and providers stigma. The primary outcome, provider stigma, was measured using the Medical Condition Regard Scale, which inquired about participants’ views on substance use and other chronic conditions. Additional survey measures included familiarity and social engagement with people with substance use disorders; clinical practices (screening, treating, and referring for a range of chronic conditions); subjective norms and social desirability; knowledge and prior education; and descriptions of their patient populations.

Results: Data collection was facilitated through collaboration with the National Opinion Research Center between October 2020 and October 2022. The overall Council of American Survey Research Organizations completion rate was 53.62% (1240/2312.7; physicians overall: 855/1681.9, 50.83% [primary care physicians: 506/1081.3, 46.79%; emergency medicine physicians: 349/599.8, 58.2%]; dentists: 385/627.1, 61.4%). The ineligibility rate among those screened is applied to those not screened, causing denominators to include fractional numbers.

Conclusions: Using systematically quantified data on the prevalence and intensity of provider stigma toward substance use disorders in health care, we can provide evidence-based improvement strategies and policies to inform the development and implementation of stigma-reduction interventions for providers to address their perceptions and treatment of substance use.

Related protocols: CTN-0104

As overdose rates rise among non-White Americans, understanding barriers to substance use disorder (SUD) treatment access by race and ethnicity is important. This study explores self-reported barriers to SUD treatment by race and ethnicity in emergency department (ED) populations.

We conducted a secondary, exploratory analysis of a randomized trial of patients not seeking SUD treatment who endorsed active drug use at six academic EDs (CTN-0047). Responses to the Barriers to Treatment Inventory were compared by race, ethnicity, and drug severity, using 2 tests (N = 858), followed by adjusted logistic regression models.

Absence of a perceived drug problem (39% non-Hispanic Black, 38% Hispanic, 50% non-Hispanic White; p = .001) was the most prevalent barrier to SUD treatment. Non-Hispanic Black participants were less likely to state that they could handle their drug use on their own (OR = 0.69, CI = 0.50-0.95), and were more likely to report disliking personal questions than non-Hispanic White participants (OR = 1.49, CI = 1.07-2.09). Non-Hispanic Black participants were less likely than Hispanic participants to agree that treatment availability (OR = 0.46, CI = 0.28-0.76) and family disapproval (OR = 0.38, CI = 0.16-0.91) were treatment barriers.

Conclusions: Screening and counseling may help address the barrier, common to all groups, that drug use was not seen as problematic. Expanding access to diverse treatment options may also address the range of barriers reported by our study population. This study is one of the first in the U.S. to examine both individual and structural barriers to accessing treatment and to examine the association with drug use severity by race/ethnicity.

Related protocols: CTN-0047

Patients with opioid use disorder (OUD) have increased emergency and hospital utilization. The PROUD trial showed that implementation of office-based addiction treatment (OBAT) increased OUD medication treatment compared to usual care, but did not decrease acute care utilization in patients with OUD documented pre-randomization (clinicaltrials.gov/study/NCT03407638). This paper reports secondary emergency and hospital utilization outcomes in patients with documented OUD in the PROUD trial.

This cluster-randomized implementation trial was conducted in 12 clinics from 6 diverse health systems (March 2015-February 2020). Patients who visited trial clinics and had an OUD diagnosis within 3 years pre-randomization were included in primary analyses; secondary analyses added patients with OUD who were new to the clinic or with newly-documented OUD post-randomization. Outcomes included days of emergency care and hospital utilization over 2 years post-randomization. Explanatory outcomes included measures of OUD treatment. Patient-level analyses used mixed-effect regression with clinic-specific random intercepts.

Among 1988 patients with documented OUD seen pre-randomization (mean age 49, 53% female), days of emergency care or hospitalization did not differ between intervention and usual care; OUD treatment also did not differ. In secondary analyses among 1347 patients with OUD post-randomization, there remained no difference in emergency or hospital utilization despite intervention patients receiving 32.2 (95% CI 4.7, 59.7) more days of OUD treatment relative to usual care.

Conclusions: Implementation of OBAT did not reduce emergency or hospital utilization among patients with OUD, even in the sample with OUD first documented post-randomization in whom the intervention increased treatment.

Related protocols: CTN-0074

Buprenorphine is an effective yet underused treatment for opioid use disorder (OUD). The goal of this study, part of CTN-0099 (Emergency Department-INitiated bupreNOrphine and VAlidaTIOn Network Trial: ED-INNOVATION), was to evaluate the feasibility (acceptability, tolerability, and safety) of 7-day injectable extended-release buprenorphine in patients with minimal to mild opioid withdrawal.

This nonrandomized trial comprising 4 emergency departments in the Northeast, mid-Atlantic, and Pacific geographic areas of the US included adults aged 18 years or older with moderate to severe OUD and Clinical Opiate Withdrawal Scale (COWS) scores less than 8 (minimal to mild), in which scores range from 0 to 7, with higher scores indicating increasing withdrawal. Exclusion criteria included methadone-positive urine, pregnancy, overdose, or required admission. Outcomes were assessed at baseline, daily for 7 days by telephone surveys, and in person at 7 days. Patient recruitment occurred between July 13, 2020, and May 25, 2023.

The intervention was injection of a 24-mg dose of a weekly extended-release formulation of buprenorphine (CAM2038) and referral for ongoing OUD care. Primary feasibility outcomes included the number of patients who (1) experienced a 5-point or greater increase in the COWS score or (2) transitioned to moderate or greater withdrawal (COWS score =13) within 4 hours of extended-release buprenorphine or (3) experienced precipitated withdrawal within 1 hour of extended-release buprenorphine. Secondary outcomes included injection pain, satisfaction, craving, use of nonprescribed opioids, adverse events, and engagement in OUD treatment.

A total of 100 adult patients were enrolled (mean [SD] age, 36.5 [8.7] years; 72% male). Among the patients, 10 (10.0% [95% CI, 4.9%-17.6%]) experienced a 5-point or greater increase in COWS and 7 (7.0% [95% CI, 2.9%-13.9%]) transitioned to moderate or greater withdrawal within 4 hours, and 2 (2.0% [95% CI, 0.2%-7.0%]) experienced precipitated withdrawal within 1 hour of extended-release buprenorphine. A total of 7 patients (7.0% [95% CI, 2.9%-13.9%]) experienced precipitated withdrawal within 4 hours of extended-release buprenorphine, which included 2 of 63 (3.2%) with a COWS score of 4 to 7 and 5 of 37 (13.5%) with a COWS score of 0 to 3. Site pain scores (based on a total pain score of 10, in which 0 indicated no pain and 10 was the worst possible pain) after injection were low immediately (median, 2.0; range, 0-10.0) and after 4 hours (median, 0; range, 0-10.0). On any given day among those who responded, between 29 (33%) and 31 (43%) patients reported no cravings and between 59 (78%) and 75 (85%) reported no use of opioids; 57 patients (60%) reported no days of opioid use. Improving privacy (62%) and not requiring daily medication (67%) were deemed extremely important. Seventy-three patients (73%) were engaged in OUD treatment on day 7. Five serious adverse events occurred that required hospitalization, of which 2 were associated with medication.

Conclusions: This nonrandomized trial of the feasibility of a 7-day buprenorphine injectable in patients with minimal to mild opioid withdrawal (COWS scores, 0-7) found the formulation to be acceptable, well tolerated, and safe in those with COWS scores of 4 to 7. This new medication formulation could substantially increase the number of patients with OUD receiving buprenorphine.

Related protocols: CTN-0099

Emergency departments (ED) are incorporating Peer Support Specialists (PSSs) to help with patient care for substance use disorders (SUDs). Despite rapid growth in this area, little is published regarding workflow, expectations of the peer role, and core components of the PSS intervention. This study describes these elements in a national sample of ED-based peer support intervention programs.

A survey was conducted to assess PSS site characteristics as part of site selection process for a National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) study evaluating PSS effectiveness (CTN-0107). Surveys were distributed to clinical sites affiliated with the 16 CTN nodes. Surveys were completed by a representative(s) of the site and collected data on the PSS role in the ED including details regarding funding and certification, services rendered, role in medications for opioid use disorder (MOUD) and naloxone distribution, and factors impacting implementation and maintenance of ED PSS programs. Quantitative data was summarized with descriptive statistics. Free-text fields were analyzed using qualitative content analysis.

A total of 11 surveys were completed, collected from 9 different states. ED PSS funding was from grants (55%), hospital funds (46%), peer recovery organizations (27%) or other (18%). Funding was anticipated to continue for a mean of 16 months (range 12 to 36 months). The majority of programs provided “general recovery support (81%) Screening, Brief Intervention, and Referral to Treatment (SBIRT) services (55%), and assisted with naloxone distribution to ED patients (64%). A minority assisted with ED-initiated buprenorphine (EDIB) programs (27%). Most (91%) provided services to patients after they were discharged from the ED. Barriers to implementation included lack of outpatient referral sources, barriers to initiating MOUD, stigma at the clinician and system level, and lack of ongoing PSS availability due to short-term grant funding.

Conclusions: The majority of ED-based PSSs were funded through time-limited grants, and short-term grant funding was identified as a barrier for ED PSS programs. There was consistency among sites in the involvement of PSSs in facilitation of transitions of SUD care, coordination of follow-up after ED discharge, and PSS involvement in naloxone distribution.

Related protocols: CTN-0107

Used as a veterinary sedative and not approved for human use, xylazine has been increasingly linked with opioid overdose deaths in the United States. A growing number of people have been exposed to xylazine in the illicit opioid supply (especially fentanyl) or in other drugs, particularly in some areas of the Northeast. Xylazine is an a-2 adrenergic agonist that decreases sympathetic nervous system activity. When combined with fentanyl or heroin, it is purported to extend the duration of the opioid’s sedative effect and to cause dependence and an associated withdrawal syndrome; however, data to support these concerns are limited. Despite the escalating frequency of detection of xylazine in people with nonfatal and fatal opioid overdose, direct links to these outcomes have not been identified. Because the strongest causal link is to fentanyl coexposure, ventilatory support and naloxone remain the cornerstones of overdose management. Xylazine is also associated with severe tissue injury, including skin ulcers and tissue loss, but little is known about the underlying mechanisms. Nonetheless, strategies for prevention and treatment are emerging. The significance and clinical effects of xylazine as an adulterant is focused on 4 domains that merit further evaluation: fentanyl-xylazine overdose, xylazine dependence and withdrawal, xylazine-associated dermal manifestations, and xylazine surveillance and detection in clinical and nonclinical settings.

This report reflects the Proceedings of the National Institute on Drug Abuse Center for the Clinical Trials Network convening of clinical and scientific experts, federal staff, and other stakeholders to describe emerging best practices for treating people exposed to xylazine-adulterated opioids. Participants identified scientific gaps and opportunities for research to inform clinical practice in emergency departments, hospitals, and addiction medicine settings.