Project Summary Abstract An estimated 15 million Americans have an alcohol use disorder (AUD), resulting annually in 95,000 deaths from alcohol-related causes and 250 billion dollars in economic burden. Yet, epidemiologic studies have consistently found that the vast majority of those with AUD are not receiving any evidence-based treatments. One of the consequences of an untreated AUD is the need for medical treatment to address the acute and chronic effects of heavy drinking, which has resulted in the number of alcohol-related emergency department (ED) visits to increase by 61.6% from 3.1 million to 5.0 million. This makes the ED an important and timely setting to engage individuals with AUD to enter addiction treatment as evidenced by the success of behavioral interventions like Screening, Brief Intervention and Referral to Treatment (SBIRT). However, SBIRT has not been as impactful for those with severe AUD, and it has been difficult for many EDs to successfully implement and sustain brief interventions. As such, more effective strategies that can be implemented in the ED setting to address AUD are critically needed. Ketamine has emerged as a potential treatment option for AUD. Ketamine has garnered interest due to its potential in treating psychiatric disorders, rapidly diminishing depressive and suicidal symptoms among individuals with treatment-resistant depression. Sub-anesthetic doses of ketamine administered in either single or multiple sessions in conjunction with psychotherapy has shown beneficial effects for patients with alcohol, opioid, and cocaine use disorders. A major advantage of ketamine is that it is already an accepted pharmacotherapy used routinely in the ED for procedural sedation, agitation, and acute pain. If ketamine could be used as an effective pharmacotherapy for AUD in the ED, the approach would be consistent with Screening, Treatment Initiation, and Referral (STIR) which may be more beneficial for patients with severe AUD than the traditional SBIRT approach. However there remains a significant gap in understanding the safety of ED-initiated ketamine in improving AUD-related outcomes for those who seek detoxification. To fill this need, we propose to conduct a pilot double-blind placebo-controlled randomized clinical trial with the primary aim of assessing the safety of administering ketamine in the ED to AUD patients seeking admission to an inpatient detoxification unit. All participants will receive the hospital’s standard detoxification treatment which also includes intensive psychosocial support. Participant selection will focus on ensuring the exclusion of those with potential medical and psychiatric co-morbidities that pose a risk when administered ketamine. Eligible participants will be randomly assigned to receive either a single infusion of ketamine or saline placebo in the ED. Vital signs, adverse effects, alcohol withdrawal, and craving for alcohol and ketamine will be monitored closely throughout the tria...