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]), history of Raynaud's phenomenon, seizures, an open cut, sore, or bone fracture on or near the hands to be used for the cold pressor test.
• Use of more than incidental NSAIDs (including aspirin), anti-inflammatories, immune suppressants or other pain medications.
• Significant active physical illness, particularly if it may affect the brain biology being studied; including chronic pain syndrome and medically compromising eating disorders or epilepsy.
• Lacks capacity to consent
• Aggressive behavior that is a significant threat to others such as physically assaultive behavior (in the last month).
• Pregnancy, abortion or miscarriage in the previous two months or plans to conceive during the course of study participation.
• Currently lactating
• Previous head injury with evidence of cognitive impairment. Subjects who endorse a history of prior head trauma and score 1.5 standard deviations below the mean on Trail-making A or B will be excluded from study participation.
• Any condition or material in the body that is a contraindication for MRI procedures.
• Current, past or anticipated exposure to radiation except if the exposure was at our PET center where the precise exposure is known
• ECT within past 6 months
• For A-Line Subjects: Unstable relevant medical condition (i.e., condition not adequately stabilized for 3 months). Including bleeding disorders, the need to take medications that affect blood clotting, and certain platelet and hemoglobin cutoffs
• Blind or with visual impairment that cannot be corrected with corrective lenses (glasses or contact lenses)
• No emergency contact