An Electrophysiological Examination of CB1 and NMDA Receptors in Humans
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- EEG Measures 2
研究概览
简要总结
The aim of the research protocol is to evaluate cannabinoid-glutamate interactions in humans. As part of this aim the investigators will assess the safety and tolerability of the combination of NMDA antagonist, ketamine, and the cannabinoid, delta-9-tetrahydrocannabinol (THC), in healthy adult subjects, and characterize the interactive effects of ketamine and THC on various electrophysiological (EEG), cognitive, and behavioral outcomes.
详细描述
The investigators will examine the contributions of the cannabinoid receptor (CB1R) and N-methyl D-aspartate receptor (NMDAR) systems to psychosis in healthy humans beings using THC and ketamine respectively (both alone and in combination). Healthy subjects (n=21) will receive THC (active or placebo) followed by ketamine (active or placebo) in a double blind, randomized, crossover (2x2) design. Psychotomimetic effects will be assessed before and at various time points after the drug infusions. EEG indices of information processing, specifically neural oscillations, will be assessed during peak drug effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •18 to approximately 45 years old
- •Good physical and mental health as determined by history, the Structured Clinical Interview for DSM-5 TR (SCID-NP) and collateral information, physical and laboratory examinations, ECG and vital signs.
- •Weight of 100 kg (220.46 lbs.) or less (inclusive).
排除标准
- •Unstable serious medical conditions. At the discretion of the investigator, subjects with unstable medical conditions that may necessitate changes in medical treatment and hence influence study outcomes will be excluded.
- •Uncontrolled hypertension, long QT syndrome, and seriously abnormal EKG results. EKG abnormalities will be reviewed by the PI and eligibility decisions will be made at the discretion of the PI.
- •A hearing deficit in greater than one band in an ear detected using a Welch-Allyn audioscope (500, 1000, 2000 and 4000 Hz threshold will be evaluated)
- •Positive pregnancy test
研究组 & 干预措施
Active Delta-9-THC and Placebo Ketamine
Active IV Delta-9-THC and Placebo Ketamine
干预措施: Active Delta-9-THC (Drug)
Active Delta-9-THC and Placebo Ketamine
Active IV Delta-9-THC and Placebo Ketamine
干预措施: Placebo Ketamine (Drug)
Active Delta-9-THC and Active Ketamine
Active IV Delta-9-THC and Active Ketamine
干预措施: Active Delta-9-THC (Drug)
Active Delta-9-THC and Active Ketamine
Active IV Delta-9-THC and Active Ketamine
干预措施: Active Ketamine (Drug)
Placebo Delta-9-THC and Placebo Ketamine
IV Placebo Delta-9-THC and Placebo Ketamine
干预措施: Placebo Delta-9-THC (Drug)
Placebo Delta-9-THC and Placebo Ketamine
IV Placebo Delta-9-THC and Placebo Ketamine
干预措施: Placebo Ketamine (Drug)
Placebo Delta-9-THC and Active Ketamine
IV Placebo Delta-9-THC and Active Ketamine
干预措施: Placebo Delta-9-THC (Drug)
Placebo Delta-9-THC and Active Ketamine
IV Placebo Delta-9-THC and Active Ketamine
干预措施: Active Ketamine (Drug)
结局指标
主要结局
EEG Measures 2
时间窗: 0-60 minutes after the onset of drug infusion
The primary EEG outcome 2 will be EEG event related potential latency (milliseconds).
EEG Measures 5
时间窗: 0-60 minutes after the onset of drug infusion
The primary EEG outcome 5 will be neural noise (Lempel Ziv Complexity).
Neurochemical Measures: THC levels
时间窗: -30, +25, +60, +120 minutes after start of drug infusion (0)
THC blood levels (ng/mL) will be assayed to determine the relationships between blood levels and EEG measures (outcomes 1-5) and behavioral measures (outcomes 10-12). Blood sampled at 4 time-points will be centrifuged and the resultant plasma will be aliquoted into appropriate vials and stored at -80 degrees C until the time of the assay.
Neurochemical Measures: THC-COOH levels
时间窗: -30, +25, +60, +120 minutes after start of drug infusion (0)
THC-COOH blood levels (ng/mL) will be assayed to determine the relationships between blood levels and EEG measures (outcomes 1-5) and behavioral measures (outcomes 10-12). Blood sampled at 4 time-points will be centrifuged and the resultant plasma will be aliquoted into appropriate vials and stored at -80 degrees C until the time of the assay.
EEG Measures 4
时间窗: 0-60 minutes after the onset of drug infusion
The primary EEG outcome 4 will be Intertrial Coherence (phase locking factor).
Neurochemical Measures: ketamine/norketamine levels
时间窗: -30, +25, +60, +120 minutes after start of drug infusion (0)
Ketamine/norketamine blood levels (ng/mL) will be assayed to determine the relationships between blood levels and EEG measures (outcomes 1-5) and behavioral measures (outcomes 10-12). Blood sampled at 4 time-points will be centrifuged and the resultant plasma will be aliquoted into appropriate vials and stored at -80 degrees C until the time of the assay.
Genetics
时间窗: Collected at the screening visit.
Blood samples for DNA extraction will be collected to examine whether any of the genes e.g., calcyon, BDNF, neuregulin-1, dysbindin, NOTCH4, COMT and the 22q11 PRODH2/DGCR6 locus that have been associated with schizophrenia, modify the effects of delta-9-THC, ketamine or the combination.
EEG Measures 1
时间窗: 0-60 minutes after the onset of drug infusion
The primary EEG outcome 1 will be EEG event related potential voltage amplitude (microvolts).
EEG Measures 3
时间窗: 0-60 minutes after the onset of drug infusion
The primary EEG outcome 3 will be spectral power (microvolts squared).
次要结局
- Positive and Negative Symptoms Scale (PANSS)(-60, +70, +120, +240 from baseline (0) (units in minutes).)
- Perceptual Alterations(-60, +70, +120, +240 from baseline (0) (units in minutes).)
- Cannabis Subjective Effects(-60, +70, +120, +240 from baseline (0) (units in minutes).)
研究者
Rajiv Radhakrishnan, MD
Assistant Professor
Yale University