Clinical trial NCT03475277: Stanford Regulating Circuits of the Brain Study- Ketamine
Official title: Mapping the Influence of Drugs of Abuse on Risk and Reward Circuits
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Healthy
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2018-03-23
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Observational model: OTHER
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Healthy volunteers with prior exposure to ketamine

Brief summary: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Circuit activation as assessed by functional magnetic resonance imaging
timeFrame: Up to 2 weeks after infusion of ketamine or placebo
Secondary outcomes:
measure: Behavioral responses on the WebNeuro computerized test battery assessing cognitive capacity
timeFrame: Up to 5 hours after infusion of ketamine or placebo
measure: Self-reported responses as assessed by the 21-item Depression, Anxiety and Stress Scale (DASS)
timeFrame: Up to 5 hours after infusion of ketamine or placebo
measure: Level of subjectively experienced intoxication, dissociation, and mood and feelings as assessed by rating scale.
timeFrame: Up to 5 hours after infusion of ketamine or placebo
measure: Self-reported responses as assessed by the 29-item Rotter's Locus of Control (RLoC)
timeFrame: Up to 5 hours after infusion of ketamine or placebo
measure: Self-reported responses as assessed by the 15-item Mini Brief Risk-Resilience Index for Screening (BRISC).
timeFrame: Up to 5 hours after infusion of ketamine or placebo
measure: Self-reported responses as assessed by the 14-item Snaith-Hamilton Please Scale (SHAPS).
timeFrame: Up to 5 hours after infusion of ketamine or placebo
measure: Self-reported responses as assessed by the 24-item Dimensional Apathy Scale (DAS).
timeFrame: Up to 5 hours after infusion of ketamine or placebo
measure: Self-reported responses as assessed by the 18-item Motivation and Pleasure Scale Self-Report (MAP-SR).
timeFrame: Up to 5 hours after infusion of ketamine or placebo
measure: Self-reported responses as assessed by the 17-item Dimensional Anhedonia Rating Scale (DARS).
timeFrame: Up to 5 hours after infusion of ketamine or placebo
measure: Self-reported responses as assessed by the 94-item 5-Dimensional Altered States of Consciousness Rating Scale (DASC).
timeFrame: Up to 5 hours after infusion of ketamine or placebo
measure: Self-reported responses as assessed by the 23-item Clinician Administered Dissociative States Scale (CADSS).
timeFrame: Up to 5 hours after infusion of ketamine or placebo
measure: Self-reported responses as assessed by a clinician on the 18-item Brief Psychiatric Rating Scale (BPRS).
timeFrame: Up to 5 hours after infusion of ketamine or placebo
measure: Steroid hormone assay via saliva collection
timeFrame: Up to 5 hours after infusion of ketamine or placebo
Other outcomes:
Locations:
city: Palo Alto
country: United States
facility: Stanford Psychiatry
state: California
Study officials:
affiliation: Study PI
name: Leanne M Williams, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.