Understanding Effects of Cannabis Use and Abstinence on Neural Glutamate Homeostasis
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Change in Metabotropic Glutamate Receptor 5 (mGluR5) Availability
研究概览
简要总结
This study will be the first in vivo human multimodal neuroimaging study exploring the relationship between mGluR5 availability (PET), neural oscillations (EEG), and cognitive function in people with CUD. The goal is to test the overall hypothesis that mGluR5 availability is higher in people with CUD compared with HC. In Aim 1, the investigators will determine differences in mGluR5 availability between people with CUD and HC in the fronto-limbic brain circuit. Aim 2 examines the associations between mGluR5 availability, CUD severity, neural oscillations, and cognitive function in CUD subjects. Aim 3 will determine how prolonged abstinence from chronic cannabis use affects mGluR5 availability, neural oscillations, and cognitive function in CUD subjects.
详细描述
Cannabis use and availability continue to rise significantly in the US. It is critical to expand our knowledge of the negative and positive effects of cannabis to "catch up" to the current reality of widespread and growing use. Cannabis and tetrahydrocannabinol (THC), its primary psychoactive chemical, have widespread effects on neural glutamate homeostasis, and specifically metabotropic glutamate receptor 5 (mGluR5). mGluR5 regulates transmission of glutamate and plays a critical role in neural plasticity (i.e., long-term potentiation; LTP), memory, learning, mood, and addiction. Specifically, it is thought that mGluR5 activation by glutamate initiates production of endocannabinoids (i.e., 2-AG) that bind retrograde to presynaptic cannabinoid receptor 1. This pathway inhibits further glutamate release and modulates synaptic plasticity diffusely in the brain. However, cannabis use disrupts this normal mechanism of glutamate homeostasis. While the relationship between cannabis use and glutamate regulation has been explored in preclinical models, it has not been well-characterized in humans, and particularly in people with cannabis use disorder (CUD).
The goal is to test the overall hypothesis that mGluR5 availability is higher in people with CUD compared with HC. This study will advance our understanding of cannabis effects on the neural glutamate system in humans and may lead to the development of novel therapeutics and biomarkers to treat people with CUD. Aim 1 will determine differences in mGluR5 availability between people with CUD and HC in the fronto-limbic brain circuit. Aim 2 examines the associations between mGluR5 availability, CUD severity, neural oscillations, and cognitive function in CUD subjects. Aim 3 will determine how prolonged abstinence from chronic cannabis use affects mGluR5 availability, neural oscillations, and cognitive function in CUD subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •HC and CUD Group:
- •Voluntary, written, informed consent
- •Physically healthy by medical history, physical, neurological, ECG and laboratory exams
- •No personal or first-degree relative history of psychiatric disorders (outside of cannabis use for CUD group)
- •Full scale and verbal IQs > 80 (Wechsler Adult Intelligence Scale, Fourth Edition; WAIS-IV).
- •Cannabis use disorder as determined by DSM-5 structured interviews
- •Urine toxicology evidence of cannabinoid use
- •lifetime cannabis exposure less than 20 times
- •no cannabis use in the past 2 years by self-report
- •a negative urine drug screen.
排除标准
- •Other substance use disorder within 1 year, except for nicotine
- •Another primary DSM-5 Axis I major psychiatric disorder (e.g., schizophrenia, bipolar disorder, major depression, etc.) per SCID-5
- •Urine toxicology results positive for other drugs such as opiates / opiate metabolites (e.g., methadone, buprenorphine, etc.)
- •A history of significant medical (cardiac, infectious, metabolic) or neurological illness (e.g., cerebrovascular disease, traumatic brain injury)
- •A history of seizures/epilepsy
- •Current use of psychotropic and/or potentially psychoactive prescription medications
- •Medical contraindications to MRI imaging (e.g., ferromagnetic implants/foreign bodies, claustrophobia, etc.)
- •Pregnancy or breastfeeding (women).
- •Subjects will be excluded for major medical or neurological illness or laboratories consistent with these illnesses or suggesting contraindication to PET or MR imaging
研究组 & 干预措施
Cannabis use disorder
CUD participants participants undergo neuroimaging, cognitive testing, and EEG at baseline and following cannabis abstinence at 4 weeks follow-up. Participants will receive motivational enhancement and contingency management during the 4-week abstinence period.
干预措施: [18F]FPEB with PET (Drug)
Cannabis use disorder
CUD participants participants undergo neuroimaging, cognitive testing, and EEG at baseline and following cannabis abstinence at 4 weeks follow-up. Participants will receive motivational enhancement and contingency management during the 4-week abstinence period.
干预措施: Cannabis abstinence (Behavioral)
Healthy control
Healthy control participants undergo neuroimaging, cognitive testing, and EEG at baseline.
干预措施: [18F]FPEB with PET (Drug)
结局指标
主要结局
Change in Metabotropic Glutamate Receptor 5 (mGluR5) Availability
时间窗: Baseline and Day 28
Participants will undergo a Positron Emission Tomography (PET) scan to visualized mGluR5 availability in the regions of interest (ROIs): orbitofrontal cortex (OFC), anterior cingulate, ventromedial prefrontal cortex (vmPFC), dorsolateral prefrontal cortex (dlPFC), hippocampus, and amygdala. Only done at baseline for HC group.
次要结局
- Change in Neurocognitive Function Using CogState Cognitive Battery(Baseline and Day 28)
- Change in Verbal Memory Measured Using Electroencephalography (EEG)(Baseline and Day 28)
研究者
Stephen Baldassarri
Assistant Professor of Medicine
Yale University