Stanford Regulating Circuits of the Brain Study- Ketamine

Primary Outcomes

• Circuit activation as assessed by functional magnetic resonance imaging Up to 2 weeks after infusion of ketamine or placebo

  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

Secondary Outcomes

• Behavioral responses on the WebNeuro computerized test battery assessing cognitive capacity Up to 5 hours after infusion of ketamine or placebo

  Accuracy data are quantified as number of errors and lower values indicate better performance

• Self-reported responses as assessed by the 21-item Depression, Anxiety and Stress Scale (DASS) Up to 5 hours after infusion of ketamine or placebo

  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

• Level of subjectively experienced intoxication, dissociation, and mood and feelings as assessed by rating scale. Up to 5 hours after infusion of ketamine or placebo

  Responses will be quantified in intervals of 10 on a visual analogue of 1 to 100

• Self-reported responses as assessed by the 29-item Rotter's Locus of Control (RLoC) Up to 5 hours after infusion of ketamine or placebo

  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.

• Self-reported responses as assessed by the 15-item Mini Brief Risk-Resilience Index for Screening (BRISC). Up to 5 hours after infusion of ketamine or placebo

  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.

• Self-reported responses as assessed by the 14-item Snaith-Hamilton Please Scale (SHAPS). Up to 5 hours after infusion of ketamine or placebo

  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.

• Self-reported responses as assessed by the 24-item Dimensional Apathy Scale (DAS). Up to 5 hours after infusion of ketamine or placebo

  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.

• Self-reported responses as assessed by the 18-item Motivation and Pleasure Scale Self-Report (MAP-SR). Up to 5 hours after infusion of ketamine or placebo

  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.

• Self-reported responses as assessed by the 17-item Dimensional Anhedonia Rating Scale (DARS). Up to 5 hours after infusion of ketamine or placebo

  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.

• Self-reported responses as assessed by the 94-item 5-Dimensional Altered States of Consciousness Rating Scale (DASC). Up to 5 hours after infusion of ketamine or placebo

  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.

• Self-reported responses as assessed by the 23-item Clinician Administered Dissociative States Scale (CADSS). Up to 5 hours after infusion of ketamine or placebo

  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.

• Self-reported responses as assessed by a clinician on the 18-item Brief Psychiatric Rating Scale (BPRS). Up to 5 hours after infusion of ketamine or placebo

  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.

• Steroid hormone assay via saliva collection Up to 5 hours after infusion of ketamine or placebo

  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.