Routine use of prescribed medications for OUD (5+ days/week) for longer than the 14 days leading up to clinic intake

Pregnant and/or breastfeeding

**Stage 2 Hypertension, defined by a systolic blood pressure (SBP) > 140mmHg or a diastolic blood pressure (DBP) > 90 mmHg

Abnormal oxygen saturation or abnormal heart rate (i.e. O2 saturation <95%, or HR <60 or >100bpm)

Clinically significant abnormal findings for which study participation is deemed unsafe

Severe mental illness or psychiatric disorder for which study participation is deemed unsafe (except for depression, PTSD, and substance use disorder)

**ALT/AST > 3 x Upper Limit of Normal (ULN), ALP 2 x ULN, or total bilirubin > 1.5 x ULN. Source: Labs

History of hypersensitivity to ketamine

Suicidal ideation with a plan or intent or suicidal behaviors as reflected in Columbia-Suicide Severity Rating Scale (C-SSRS)

Recent homicidal ideation or violent behaviors

Concomitant daily use of medications with significant CYP2B6 and CYP3A4 inhibition or induction effects that can interfere with metabolism of ketamine

Advanced cardiopulmonary disorders, including stroke, cardiac arrest, and myocardial infarction in the past year

History of aneurysmal vascular disease or dissection (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation

**Clinically significant EKG abnormalities.

Current significant use (>3 days/week) of barbiturates, sedative hypnotics, benzodiazepines, ketamine, or PCP (prescribed or illicit)

• NOTE: Due to time constraints in the study design, these exclusion criteria do not need to be met before the initial consent to participate. This criterion only needs to be established prior to the first ketamine session. Individuals that are initially enrolled and subsequently do not qualify due to severe hepatic impairment will be considered screen failures and withdrawn from the protocol.