Understanding the Role of the Kappa Opioid Receptor in Ketamine's Attenuation of Suicidal Thoughts

Inclusion Criteria: * DSM5 unipolar major depressive episode * Persons of child-bearing potential must agree to use an acceptable method of birth control throughout the study. Exclusion Criteria: * Current or past ketamine abuse or dependence ever (lifetime) * Any medical contraindication to ketamine, including prior ineffective trial of or medically significant adverse reaction to ketamine. * Clinically significant EKG abnormality in terms of ketamine administration (e.g., Ventricular tachycardia, evidence of myocardial ischemia, symptomatic bradycardia, unstable tachycardia, second degree (or greater) AV block). * Lifetime schizophrenia, schizoaffective illness, bipolar disorder, current psychotic depression; mild drug or alcohol use disorder in past 2 months; moderate or severe drug or alcohol use disorder in past 6 months; suicidal ideation with plan and/or intent within 6 months; suicide attempt in the past month. * A first-degree family history of schizophrenia if the subject is less than 33 years old (mean age of onset for schizophrenia plus two standard deviations). * Current or recent use of antidepressants within 14 days or benzodiazepines within 1 day. Use of fluoxetine or other long-acting antidepressant within 6 weeks. * Current or recent use of medications known to affect brain biology of interest such as competing for binding sites of PET tracer within 1 month. * Uncontrolled moderate or severe hypertension (≥160 mmHg systolic or ≥100 mmHg diastolic\[41\]), …