The Effect of Brief Potent Glutamatergic Modulation on Disordered Alcohol Use

短暂有效的谷氨酸能调节对酒精滥用的影响

基本信息

批准号：
8824053
负责人：
Elias Dakwar
金额：
$ 23.29万
依托单位：
NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-10 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8824053
关键词：
Abstinence Address Adverse effects Affinity Alcohol abuse Alcohol consumption Alcohol dependence Alcohol or Other Drugs use Alcohols Anesthetics Anterior Attenuated Back Breath Tests Clinic Clinical Clinical Trials Cocaine Cocaine Dependence Cocaine Users Coupled Cues Data Dependence Depression and Suicide Disease Disease remission Dose Drug usage Drug user Evaluation Evidence based treatment Exploratory/Developmental Grant Functional disorder Glutamates Goals Heavy Drinking Hour Impulsivity Individual Infusion procedures Intervention Intravenous Intravenous infusion procedures Investigation Ketamine Link Lorazepam Measures Methods Midazolam Motivation N-Methylaspartate National Institute of Mental Health Neuronal Plasticity Outcome Outpatients Participant Pharmaceutical Preparations Pharmacotherapy Protocols documentation Public Health Randomized Refractory Relapse Research Research Personnel Rhode Island Risk Self Efficacy Stress Testing Therapeutic Effect Visual Withdrawal Woman active control addiction alcohol abstinence alcohol abuse therapy alcohol use disorder analog breath alcohol measurement cingulate cortex clinically relevant cocaine use craving drinking follow-up improved innovation interest men mindfulness motivational enhancement therapy neuroadaptation neurotransmission novel public health relevance reduced alcohol use time use treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Alterations in glutamate neurotransmission are recognized as an important target of pharmacotherapy for alcohol dependence. Our preliminary investigations with ketamine, a glutamate modulator with potent prefrontal effects, suggest that it uniquely addresses neuroadaptations related to problematic drug and alcohol use. Alongside being safely administered to active drug users, we found that sub-anesthetic ketamine significantly increased motivation to stop cocaine use and decreased cue-induced craving when compared to an active control, 24 hours post-infusion. An ongoing clinical trial also indicates that ketamine can be feasibly administered in the setting of outpatient addiction treatment. Expanding on these findings, this project aims to examine whether ketamine will benefit problematic alcohol use in clinical settings. We will evaluate the effect of a single sub-anestheti dose of ketamine (0.11 mg/kg over 2 minutes, followed by 0.60 mg/kg over 50 minutes) on alcohol dependence in 40 non-depressed alcohol-dependent individuals engaged in Motivational Enhancement Therapy (MET). We predict that, compared to the active control midazolam, ketamine will significantly reduce percentage heavy drinking days. Secondary aims pertain to the effect of ketamine on alcohol-related deficits that implicate prefrontal dysfunction or glutamate abnormalities, such as stress sensitivity, craving, withdrawal, impulsivity, low self-efficacy, and low mindfulness. Thus, we aim to evaluate a highly innovative intervention in a manner that has the capacity to make important contributions to the field. An effect of ketamine on these outcomes would suggest that brief potent glutamatergic modulation represents a possible treatment strategy for alcohol dependence that merits further investigation.

描述（由申请人提供）：谷氨酸神经传递的改变被认为是酒精依赖性药物疗法的重要靶标。我们对具有有效前额叶作用的谷氨酸调节剂氯胺酮进行的初步研究表明，它独特地解决了与有问题的药物和酒精使用有关的神经适应。除了安全地管理活跃的吸毒者外，我们发现，与主动对照相比，接收到24小时后，亚麻省氯胺酮显着增加了停止可卡因使用并减少提示引起的渴望的动机。一项正在进行的临床试验还表明，在门诊成瘾治疗的情况下，氯胺酮可以可行地给药。随着这些发现的扩展，该项目旨在检查氯胺酮是否会在临床环境中受益于饮酒。我们将评估单个亚麻醉剂量的氯胺酮（在2分钟内0.11 mg/kg，0.11 mg/kg，然后在50分钟内为0.60 mg/kg）评估40个从事动机增强治疗（MET）的40个非抑郁酒精依赖性的个体中酒精依赖性的影响（MET）。我们预测，与主动对照咪达唑仑相比，氯胺酮将显着降低大量饮酒日的百分比。次要目的与氯胺酮对与酒精相关的缺陷的影响有关，这暗示着前额叶功能障碍或谷氨酸异常，例如压力敏感性，渴望，戒断，冲动，自我效能低下和正念低。因此，我们旨在以有能力为该领域做出重要贡献的方式评估高度创新的干预措施。氯胺酮对这些结果的影响表明，短暂的有效谷氨酸能调节代表了酒精依赖的可能治疗策略，值得进一步研究。