Inclusion Criteria  From NHS prescreen (no contact, Study Day 0): Between the ages of 18 to 65 years old From NHS prescreen (no contact, Study Day 0): Daily use of illicit opioids From NHS prescreen (no contact, Study Day 0): Fulfillment of DSM-5/ICD-10 criteria for moderate-to-severe opioid or heroin use disorder From NHS prescreen (no contact, Study Day 0): Acceptance into methadone maintenance care for treatment of opioid or heroin use disorder From screening for study eligibility (Study Contact Day 1): A total of 10 or more points on the PHQ-9 From screening for study eligibility (Study Contact Day 1): A total of 3 points or less on the PC-PTSD-5 From screening for study eligibility (Study Contact Day 1): Have had no prior sustained experience/dependence on ketamine (i.e., must answer "no" to all four questions on the ketamine screen)  Exclusion Criteria  From NHS prescreen (no contact, Study Day 0): Patients transferring from another program of opioid agonist treatment From NHS prescreen (no contact, Study Day 0): Electrocardiogram (ECG) findings of tachycardia, prior myocardial infarction, myocardial ischemia, or aberrant conduction From NHS prescreen (no contact, Study Day 0): Baseline urine drug test positive for ketamine, benzodiazepine, psychostimulants (cocaine, amphetamine, methamphetamine, or methylene-dioxymethamphetamine [MDMA]), phencyclidine (PCP), methadone, or buprenorphine From NHS prescreen (no contact, Study Day 0): Self-report of recent prescribed or illicit benzodiazepine use ("Xannies", or "bars") From NHS prescreen (no contact, Study Day 0): Urine screen positive for pregnancy From NHS prescreen (no contact, Study Day 0): Stage 2 hypertension, defined by a systolic blood pressure (SBP) > 140 mmHg or a diastolic blood pressure (DBP) > 90 mmHg From NHS prescreen (no contact, Study Day 0): Clinically significant abnormal laboratory values, physical exam findings or self-reported medical conditions for which a transient increase in blood pressure could be significantly detrimental (e.g., cardiovascular disease), as determined by the evaluating intake physician From NHS prescreen (no contact, Study Day 0): Any clinically significant abnormal findings from intake health and physical examination From NHS prescreen (no contact, Study Day 0): Any indication of serious mental illness or psychiatric disorder from the attending's evaluation notes From Liver Function Screen (Study Contact Day 2): Baseline alkaline phosphatase > 2.5 times the upper limit of normal From Liver Function Screen (Study Contact Day 2): Baseline aspartate aminotransferase > 3 times the upper limit of normal From Psychiatric Evaluation (Study Contact Day 2) Current or previous recreational use of ketamine or PCP From Psychiatric Evaluation (Study Contact Day 2): Subjects who meet DSM-5 criteria for current bipolar disorder From Psychiatric Evaluation (Study Contact Day 2): Past or current presence of psychotic symptoms, or diagnosis of a lifetime psychotic disorder including schizophrenia or schizoaffective disorder Subjects who meet DSM-5 criteria for current or history of psychotic spectrum disorders