An observational study in Healthy, sponsored by Stanford University. Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2026-01-02.
Sponsored by Stanford University · Observational
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.
Healthy volunteers with prior exposure to ketamine
Exclusion Criteria:
Participants will receive an IV infusion of ketamine (\~.05mg/kg and 0.5mg/kg) or placebo. Ketamine is an FDA-approved dissociative anesthetic. The study doses are in the subanesthetic range. During the infusion, an ACLS-certified psychiatrist or anesthesiologist will provide continuous monitoring. Afterwards, patients will be monitored on-site by an ACLS-certified MD or highly skilled research nursing staff, and an on-call emergency response team for 4 hours (ketamine's half-life is 15 min; 4 hrs= 16 half-lives).
Drug: Ketamine
Acute administration
Also known as: "special k"
Circuit activation as assessed by functional magnetic resonance imaging
During functional magnetic resonance imaging the reward and negative affect circuits will be engaged by reward and related emotional tasks, and circuit activation will be quantified by blood flow in regions of interest and the extent of functional connectivity between them
Time frame: Up to 2 weeks after infusion of ketamine or placebo
Behavioral responses on the WebNeuro computerized test battery assessing cognitive capacity
Accuracy data are quantified as number of errors and lower values indicate better performance
Time frame: Up to 5 hours after infusion of ketamine or placebo
Self-reported responses as assessed by the 21-item Depression, Anxiety and Stress Scale (DASS)
Responses are quantified on a 4-point scale and summed for total DASS score and for each Depression, Anxiety and Subscale score. Higher scores indicate more severe symptoms of depression, anxiety and stress
Time frame: Up to 5 hours after infusion of ketamine or placebo
Level of subjectively experienced intoxication, dissociation, and mood and feelings as assessed by rating scale.
Responses will be quantified in intervals of 10 on a visual analogue of 1 to 100
Time frame: Up to 5 hours after infusion of ketamine or placebo
Self-reported responses as assessed by the 29-item Rotter's Locus of Control (RLoC)
Responses are quantified as a summed score from 0 to 23 and determine the degree to which a person perceives an outcome as being contingent on their own actions or those of external forces. Higher scores indicate greater levels of external locus of control.
Time frame: Up to 5 hours after infusion of ketamine or placebo
Self-reported responses as assessed by the 15-item Mini Brief Risk-Resilience Index for Screening (BRISC).
Responses are quantified on a 5-point Likert scale and is a measure of emotional self-regulation. Scores measure three core domains: negativity bias, emotional resilience, and social skills. Higher scores indicate higher functioning and better coping.
Time frame: Up to 5 hours after infusion of ketamine or placebo
Self-reported responses as assessed by the 14-item Snaith-Hamilton Please Scale (SHAPS).
Responses are quantified on a 4-point scale and measures anhedonia, the inability to experience pleasure. Scores measure domains of social interaction, food and drink, sensory experience, and interest/pastimes. An "abnormal" score is defined as 3 or more.
Time frame: Up to 5 hours after infusion of ketamine or placebo
Self-reported responses as assessed by the 24-item Dimensional Apathy Scale (DAS).
Responses are quantified on a 4-point scale and measure demotivation in three domains: executive apathy, emotional apathy, and initiation apathy. Higher scores indicate higher apathy level.
Time frame: Up to 5 hours after infusion of ketamine or placebo
Self-reported responses as assessed by the 18-item Motivation and Pleasure Scale Self-Report (MAP-SR).
Responses are quantified on a 5-point Likert scale and assesses an individual's motivation and pleasure. Higher scores indicate higher levels of motivation and pleasure.
Time frame: Up to 5 hours after infusion of ketamine or placebo
Self-reported responses as assessed by the 17-item Dimensional Anhedonia Rating Scale (DARS).
Responses are summed on a 5-point scale. Scores assess interest, motivation, effort, and consummatory pleasure across four domains: hobbies, food/drink, social activities, and sensory experiences. Lower scores represent a higher level of anhedonia.
Time frame: Up to 5 hours after infusion of ketamine or placebo
Self-reported responses as assessed by the 94-item 5-Dimensional Altered States of Consciousness Rating Scale (DASC).
Responses are recorded on a sliding scale with one side reading 'No, not more than usually' and the opposite reading 'Yes, much more than usually'. More agreeance to the statements represents that the individual is experiencing higher levels of altered states of consciousness.
Time frame: Up to 5 hours after infusion of ketamine or placebo
Self-reported responses as assessed by the 23-item Clinician Administered Dissociative States Scale (CADSS).
Responses are summed on a 5-point scale in rating one's agreeance to the dissociative statements as 'not at all' to 'extreme'. Scores assess individual's dissociative state. A higher score represents more dissociation.
Time frame: Up to 5 hours after infusion of ketamine or placebo
Self-reported responses as assessed by a clinician on the 18-item Brief Psychiatric Rating Scale (BPRS).
Responses are summed on a 7-point scale in rating one's severity to the statements as 'not assessed' to 'extremely severe'. Scores assess psychiatric symptoms like anxiety, depression, and psychoses. A higher score means the individual is presenting more extreme symptoms.
Time frame: Up to 5 hours after infusion of ketamine or placebo
Steroid hormone assay via saliva collection
At 5 different time points throughout infusion visits the participant chews on a cotton swab for 30 seconds to collect saliva. A steroid hormone assay is conducted to collect data on cortisol, testosterone, progesterone, and estradiol levels.
Time frame: Up to 5 hours after infusion of ketamine or placebo
Plan to share: No
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Stanford University