Glutamatergic Mechanisms of Psychosis and Target Engagement (SA1)

Inclusion Criteria:

1. Age between 18-55
2. Medically healthy, as assessed by study physician
3. Capable of understanding the study procedures and able to provide informed consent
4. Eligible men and women must agree to use a reliable method of birth control (for example, use of oral contraceptives or Norplant; a reliable barrier method of birth control diaphragms with contraceptive jelly; cervical caps with contraceptive jelly; condoms with contraceptive foam; intrauterine devices; partner with vasectomy; or abstinence) during the study. Women who are post-menopausal or otherwise not of childbearing potential are also eligible.

Exclusion Criteria:

1. Current or past Axis I psychiatric history (including Substance Use Disorder/Alcohol Use Disorder, with the exception of nicotine use disorder)
2. Positive urine toxicology
3. History of recreational ketamine use, recreational PCP use, or an adverse reaction to ketamine. Subjects who have participated in prior research ketamine studies will be eligible. Subjects can have infusions not more frequently than biweekly, and not more than 1/month on average, therefore subjects entering the study will need to wait one month if they had a single infusion and 6 weeks if they have had two closely spaced infusions.
4. History of first-degree relative with schizophrenia
5. Pregnancy or breast-feeding. This exclusion criterion applies only to females of child-bearing potential (not surgically sterilized and between menarche and 1 year postmenopausal). Must test negative for pregnancy at the time of screening based on a serum pregnancy test.
6. History of violence, including any history of using a gun, knife, or other weapon with intent to harm someone, as well as a more than one physical fight without a weapon after the age of 18 years old (not including fights that happen during sports competition).
7. Presence or positive history of significant medical illness, including renal problems (GFR\<60), high blood pressure (defined as systolic blood pressure (SBP) \> 140 or diastolic blood pressure (DBP) \> 90), low blood pressure (SBP \< 100, DBP \< 60), orthostatic blood pressure at baseline (change in mean arterial pressure \[1/3 systolic + 2/3 diastolic\] of \> 20%), cardiac illness, or clinically significant abnormal screening labs, as determined by the site physician.
8. Subjects with suicidal ideation with intent or plan (indicated by affirmative answers to items 4 or 5 of the Suicidal Ideation section of the baseline C-SSRS) in the 6 months prior to screening or subjects who represent a significant risk of suicide in the opinion of the investigator.
9. Presence or positive history of neurological illness, including seizures, mental retardation or any other disease/procedure/accident/intervention associated with significant injury to or malfunction of the central nervous system (CNS), or history of significant head injury.
10. Metal implants, pacemaker, other metal (e.g., shrapnel or surgical prostheses) or paramagnetic objects contained within the body which may present a risk to the subject or interfere with the MR scan.
11. Medicinal patch, unless removed prior to the MR scan
12. Claustrophobia
13. Currently taking any psychotropic medication, including antidepressant medications, benzodiazepines, antipsychotic medications, mood stabilizers, anti-epileptic medications, and stimulants. We will exclude any subject who requires treatment with any psychotropic medication from one of these classes.