Stanford Regulating Circuits of the Brain Study- Ketamine

Mapping the Influence of Drugs of Abuse on Risk and Reward Circuits

This study is a biomarker study designed to characterize how ketamine impacts the reward circuits of the human brain.

The investigators will assess the effect of acute ketamine modulation on the functioning of reward-related human brain circuits. Reward-related brain circuits will be assessed using functional magnetic resonance imaging.

Participants will include volunteers who report more than two prior uses of ketamine (also known as "Special K"), when they were 18 years or older.

The investigators will recruit individuals who have previously tried ketamine rather than those who are ketamine-naïve.

Participants will receive an IV infusion of ketamine (~.05mg/kg and 0.5mg/kg) or placebo (saline). Following established procedures, these three sessions will be randomized in a blinded protocol in order to limit expectancy effects.

Throughout each session, participants will be monitored. Functional imaging will commence after the drug has reached peak levels, following previously established time courses for ketamine infusion. Participants will also be monitored after the functional imaging session. Secondary effects of ketamine on behavior and self-reported experience will be assessed.

In the assessment of the acute effects of ketamine, the investigators will take into account the cumulative effects of prior drug exposure.

Inclusion Criteria:

• Ages 18-55 years
• At least 2 prior uses of ketamine when aged 18+
• BMI within healthy range (18-30)
• Ability to speak, read, or understand English

Exclusion Criteria:

• Current active suicide ideation or history of suicide attempts
• Current mood, anxiety, eating, psychotic, or substance use disorder
• Lifetime psychotic or bipolar disorder
• Schizophrenia in a first degree relative
• Current use of psychotropic medication
• Prior adverse ketamine response
• Allergy or hypersensitivity to ketamine
• Use of ketamine in past 7 days
• Cannabis use in the past 7 days, illicit recreational drug use in the 48 hours prior to sessions, and/or alcohol use in the 24 hours prior to sessions
• Concurrent use of any medications that might increase the risk of participation (e.g., drug interactions)
• History of epilepsy, convulsions, seizures, LOC >10 min
• Renal/hepatic impairment
• Hypertension (Stage 1 defined as systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg on 2 of 3 measurements at least 15 min apart at initial screening; systolic blood pressure >155 mmHg or diastolic blood pressure >99 mmHg on 2 of 3 measurements at least 15 min apart during infusion visits)
• Heart rate <50 bpm or >150 bpm at initial screening
• Chronic congestive heart failure, tachyarrhythmias, myocardial ischemia assessed via EKG at initial screening
• EKG QTcF intervals >430 ms for men and >470 ms for women
• Direct physical access to or routine handling of addicting drugs in the regular course of work duties
• MRI contraindication
• Pregnant or nursing females