Mapping the Influence of Drugs of Abuse on Risk and Reward Circuits
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- Circuit activation as assessed by functional magnetic resonance imaging
研究概览
简要总结
This study is a biomarker study designed to characterize how ketamine impacts the reward circuits of the human brain.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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).
干预措施: Ketamine (Drug)
结局指标
主要结局
Circuit activation as assessed by functional magnetic resonance imaging
时间窗: 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
次要结局
- 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)
- 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)
- Behavioral responses on the WebNeuro computerized test battery assessing cognitive capacity(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)(Up to 5 hours after infusion of ketamine or placebo)
- Self-reported responses as assessed by the 14-item Snaith-Hamilton Please Scale (SHAPS).(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).(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).(Up to 5 hours after infusion of ketamine or placebo)
- Self-reported responses as assessed by the 17-item Dimensional Anhedonia Rating Scale (DARS).(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).(Up to 5 hours after infusion of ketamine or placebo)
- Steroid hormone assay via saliva collection(Up to 5 hours after infusion of ketamine or placebo)
- Self-reported responses as assessed by the 24-item Dimensional Apathy Scale (DAS).(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).(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).(Up to 5 hours after infusion of ketamine or placebo)
研究者
Leanne Williams
Professor of Psychiatry and Behavioral Sciences
Stanford University