HealthyRBRAIN-KETNCT03475277
Stanford Regulating Circuits of the Brain Study- Ketamine
An observational study of Healthy, run by Stanford University at 1 site in United States.
Trial summary
This study is a biomarker study designed to characterize how ketamine impacts the reward circuits of the human brain. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Healthy
- What is being tested?
- Ketamine
- Type of treatment
- Injection or infusion
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Aug 2019to 1 Jul 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Adult
Study population: Healthy volunteers with prior exposure to ketamine
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the detailed description
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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called "special k"
Acute administration
| Study group | Role | What they receive |
|---|---|---|
| Volunteers | 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). Receives: Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 2 weeks after infusion of ketamine or placebo
Secondary outcomes (13)
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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 5 hours after infusion of ketamine or placebo
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2018
- Study start19 Aug 2019
- Primary completion30 Nov 2022
- Study completion1 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Other
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Leanne Williams, Stanford University
- Investigators
- Leanne M Williams, PhD, Principal investigator, Study PI
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03475277
- Sponsor's protocol ID
- 41173
- Other IDs
- 1P50DA042012-01A1
- Acronym
- RBRAIN-KET
- Status last verified
- Dec 2025
- First submitted
- 1 Mar 2018
- Last updated
- 2 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Hack LM, Zhang X, Heifets BD, Suppes T, van Roessel PJ, Yesavage JA, Gray NJ, Hilton R, Bertrand C, Rodriguez CI, Deisseroth K, Knutson B, Williams LM. Ketamine's acute effects on negative brain states are mediated through distinct altered states of consciousness in humans. Nat Commun. 2023 Oct 19;14(1):6631. doi: 10.1038/s41467-023-42141-5.
PubMed 37857620
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mapping the Influence of Drugs of Abuse on Risk and Reward Circuits
- ClinicalTrials.gov ID
- NCT03475277
- Acronym / sponsor ID
- RBRAIN-KET / 41173
- Conditions
- Healthy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 19 Aug 2019 (actual)
- Primary completion
- 30 Nov 2022 (actual)
- Study completion
- 1 Jul 2024 (actual)
- First posted
- 23 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a biomarker study designed to characterize how ketamine impacts the reward circuits of the human brain.
Detailed description
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.
Study design
- Observational model
- Other
- Time perspective
- Other
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Volunteers | – | Drug: KetamineParticipants 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). |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Age groups
- Adult
- Study population
- Healthy volunteers with prior exposure to ketamine
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineAlso: "special k"Acute administration | Drug | Volunteers |
Primary outcome
Circuit activation as assessed by functional magnetic resonance imaging
Time frame: 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
13 secondary outcomes
Behavioral responses on the WebNeuro computerized test battery assessing cognitive capacity
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)
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.
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)
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).
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).
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).
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).
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).
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).
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).
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).
Time frame: Up to 5 hours after infusion of ketamine or placebo
Steroid hormone assay via saliva collection
Time frame: Up to 5 hours after infusion of ketamine or placebo
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2026.
- Results publication: PubMed 37857620Hack LM, Zhang X, Heifets BD, Suppes T, van Roessel PJ, Yesavage JA, Gray NJ, Hilton R, Bertrand C, Rodriguez CI, Deisseroth K, Knutson B, Williams LM. Ketamine's acute effects on negative brain states are mediated through distinct altered states of consciousness in humans. Nat Commun. 2023 Oct 19;14(1):6631. doi: 10.1038/s41467-023-42141-5.
- Link to results referenceLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Leanne M Williams, PhD principal investigator
Study PI
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Healthy, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Circuit activation as assessed by functional magnetic resonance imaging (time frame: Up to 2 weeks after infusion of ketamine or placebo). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03475277, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jan 2026.