Endogenous Opioid Modulation by Ketamine

Endogenous Opioid Modulation by Ketamine

Demonstrate the acute effects of ketamine on endogenous µ-opioid neurotransmission in humans.

This study will test the hypothesis that the rapidly-acting antidepressant ketamine improves core depressive symptoms by acutely activating the brain's endogenous µ-opioid system.

Inclusion Criteria:

• Age 18-65
• DSM-5 major depressive disorder
• Current moderate-to-severe, treatment-resistant, depressive episode
• Patient Health Questionnaire (PHQ-9) total score ≥ 10
• PHQ-9 item score ≥ 2 on "Little interest or pleasure" item
• PHQ-9 item score ≥ 2 on "Feeling down, depressed, or hopeless" item
• Medical documentation of depression for at least 2 months
• Inadequate response to at least one adequate antidepressant medication trial in the current episode

Exclusion Criteria:

• Current episode duration >5 years
• Moderate-to-severe DSM-5 substance use disorder (past year)
• Cognitive disorder (past year)
• Post-traumatic stress disorder (past year)
• Obsessive compulsive disorder (past year)
• Personality disorder (past year)
• Positive urine drug screen
• Psychotic symptoms
• Mania
• Significant neurologic disorder or injury
• Breastfeeding or pregnancy
• Imminent suicide risk
• Current use of CYP3A4 inhibitors (e.g., ketoconazole or erythromycin)
• Other unstable psychiatric or medical condition requiring a higher level of care
• Contraindication to ketamine, MRI, or PET