Intravenous Alcohol and THC Effects on Simulated Driving and Related Cognition

 描述(由申请人提供)：机动车辆事故(MVA)是全球发病率和死亡率的十大主要原因之一(1)。2012年，在美国境内，大约有30,000起多发性血管意外导致33,561人死亡，此外，还有1,634,000起报告的多发性多发性硬化症造成人员受伤(2)。酒精和大麻是导致驾驶障碍和MVA的重要因素。虽然酒精对驾驶的影响是众所周知的，也得到了广泛的研究(4)，但大麻或其组成的大麻对驾驶的影响还不太清楚(5)，关于酒精和大麻联合对驾驶的影响更是鲜为人知。随着娱乐和“医疗”使用大麻日益合法化，尤其是年轻人越来越认为大麻是安全的(6)，以及缺乏为公共卫生政策提供信息的实验数据，在这两种物质的影响下驾驶，有必要研究大麻和酒精对驾驶的综合影响。假设：适度的娱乐剂量的THC和乙醇的组合，将对模拟驾驶、与驾驶相关的事件相关电位(ERPs)以及与驾驶相关的认知功能造成比单独使用这两种药物更大的程度的损害。方法：在一个 随机、双盲、安慰剂对照、交叉(2x2)、平衡实验室研究，健康受试者(n=25)将同时通过单独的静脉(IV)线路接受1)静脉注射乙醇或安慰剂(生理盐水)，以在20分钟内达到0.04%的浓度(相当于1小时内2杯饮料)，并使用计算机辅助酒精输注系统保持在该水平额外60分钟，以及2)静脉注射四氢大麻酚(0.015毫克/公斤=1/4-1/2大麻关节)或安慰剂(生理盐水)20分钟。受试者将完成1)在驾驶模拟器上日夜驾驶课程，同时记录EEG以获得与驾驶错误相关的ERPs-ERn和Pe；2)EEG P300新颖性任务，以及3)与驾驶相关的认知测试(CogState)。支持可行性数据：我们拥有管理IV乙醇(n&gt；20)和THC(n&gt；400)的经验和专业知识，此外还拥有管理IV THC所需的监管批准(IND，附表1许可证)。我们已经证明，在模拟驾驶任务中，静脉注射乙醇增加了SDLP，并且还显示了静脉注射乙醇和静脉注射THC对降低P3a幅度的单独作用。

 DESCRIPTION (provided by applicant): Motor vehicle accidents (MVAs) are among the top 10 leading causes of morbidity and mortality worldwide (1). In 2012, within the United States (US) there were about 30,000 MVAs that resulted in 33,561 fatalities, in addition to 1,634,000 reported MVAs that caused injury (2). Alcohol and cannabis are very important contributors to both impaired driving and MVA's (3). While the effects of alcohol on driving are well- known and have been widely studied (4), the effects of cannabis or its constituent cannabinoids on driving are less clear (5), and there is even less known about the effects of the combination of alcohol and cannabinoids on driving. With the growing legalization of both recreational and "medical" use of cannabis, the growing perception, especially among young adults, that cannabis is safe (6), and the paucity of experimental data to inform public health policy regarding driving under the influence of both substances, there is a need to study the combined effects of cannabinoids and alcohol on driving. Hypothesis: The combination of modest recreational doses of THC and ethanol, will impair simulated driving, event related potentials (ERPs) relevant to driving, and driving related cognitive function to a greater extent than either drug individually. Methods: In a randomized, double-blind, placebo-controlled, crossover (2x2), counterbalanced laboratory study, healthy subjects (n=25) will simultaneously receive through separate intravenous (IV) lines 1) IV ethanol or placebo (saline) to reach a BrAC of 0.04% (equivalent to ~2 drinks over 1 hour) within 20 minutes and remain clamped at this level for an additional 60 minutes using a computer-assisted alcohol infusion system, and 2) IV THC (0.015 mg/kg = 1/4 - 1/2 cannabis joint) or placebo (saline) over 20 minutes. Subjects will complete 1) a day and night driving course on a driving simulator, while EEG is recorded to obtain the driving error related ERPs - ERN and Pe; 2) an EEG P300 novelty task, and 3) a battery (CogState) of cognitive tests relevant to driving. Supporting feasibility data: We have the experience and expertise, to administer IV ethanol (n>20) and THC (n>400), in addition to having the regulatory approvals (IND, Schedule 1 license) necessary to administer IV THC. We have demonstrated that IV ethanol increases SDLP on a simulated driving task, and have also shown the separate effects of both IV ethanol and IV THC on reducing amplitude of the P3a.