Abstract This administrative supplement will fund the central pharmacy and urine drug screening activities reassigned to Lead Investigators at Yale University and not previously supported in the original funded application described as follows. Drug overdoses in the U.S. increased to over 107,000 in the year ending January 2022 including > 80,000 involving opioids, representing a 24% increase from the prior year. Despite improved outcomes and decreased all-cause mortality among individuals with opioid use disorder (OUD) who receive opioid agonist treatment, only 11% of individuals with OUD receive medications for opioid use disorder. Narrowing the treatment gap by expanding access to treatment beyond specialized drug treatment settings is a public health priority, and the Emergency Department (ED), offering access 24 hours, 7 days a week, 365 days a year, is a logical point of intervention. ED patients have a disproportionately high prevalence of OUD, and for many, the ED is the primary or only access point in the healthcare system. There are currently no controlled, prospective studies comparing dosing strategies for buprenorphine induction in the ED. We propose a multisite randomized double-blind, double-dummy, clinical trial of ED patients with moderate to severe OUD (N=360) from 4 geographically diverse EDs to compare Standard ED Dose Induction (SDI; 8 mg) with High Dose Induction (HDI; 24 mg) to evaluate AIM 1: Engagement in continuing OUD treatment at 10 days and AIM 2: Differences in outcomes of craving, tolerability, withdrawal symptoms, and use of illicit drugs. We hypothesize that patients assigned to the HDI group will be more likely to be engaged in OUD treatment at 10 days post ED enrollment (primary outcome), and will describe less craving, less withdrawal symptoms and less use of illicit drugs during the 10 days post ED buprenorphine induction. Additional outcomes will be the development of ED protocols, and evaluation of safety, feasibility, and acceptability. The primary outcome of engagement in treatment at 10 days as well as treatment at day 30 will be verified by the treating clinician. Assessment of craving, withdrawal symptoms and use of illicit drugs will be obtained by daily Qualtrics phone surveys. The planned study sample and the proposed analytical methods will allow for additional meaningful exploratory evaluations of potential differential effects of gender, race, ethnicity, housing instability, insurance status, and use of fentanyl, and other polysubstance use such as stimulants, sedatives, and alcohol. An accelerated induction typical engagement process that achieves t herapeutic buprenorphine levels in less than 3-4 hours compared to the 2-3 days could potentially increase safety during the crucial gap between ED discharge and in continuation treatment by limiting illicit opioid use and encouraging follow up visits for OUD treatment.

Project Narrative This administrative supplement will fund the central pharmacy and urine drug screening activities reassigned to Lead Investigators at Yale University and not previously supported in the original funded application described as follows. The emergency department (ED) provides an opportunity to care for patients with opioid use disorder (OUD) and initiate treatment 24 hours, 365 days a year. This project will test two dosing strategies of buprenorphine, standard ED dosing versus a high dose accelerated induction process, in engaging patients with ongoing addiction treatment while evaluating treatment engagement, craving, withdrawal symptoms and use of illicit drugs.