Glutamatergic Mechanisms of Psychosis and Target Engagement (SA1)

50 healthy volunteers (HV) will participate in 2 identical ketamine-induced pharmacoBOLD (phBOLD) sessions at least 7 days apart. On both days, clinical assessments will be performed following removal of the subject from the scanner. HV will be discharged home after clearance by the study physician. This study will assign ketamine doses in successive 10 subject cohorts. The ketamine dose for the 1st cohort will start at 0.08 mg/kg. For subsequent cohorts, the bolus will be successively reduced or increased by 0.02 mg/kg (n=10/dose) to determine the lowest dose of ketamine that still produces a robust phBOLD response. The study will be subject and rater blind, i.e. subjects and raters, will be blinded to the treatment (ketamine dose) group. The study physician will be aware of the ketamine dose, and ketamine dose will be the same for both sessions. Subjects will not be told what the exact ketamine dose they will receive, but it will be based on their weight and will be no higher than 0.08 mg/kg.

NCT Number	NCT04589208
Lead Sponsor	New York State Psychiatric Institute Collaborators: National Institute of Mental Health (NIMH)
Conditions	Healthy
Enrollment	35 participants
Start Date	2021-01-01
Primary Completion	2027-01-01 (estimated)
Study Completion	2027-04-01 (estimated)
Updated on ClinicalTrials.gov	2026-07-13