Simulated Driving Under the Influence of Marijuana: an fMRI Study

描述(由申请人提供)：尽管人们普遍认为大麻(MJ)会损害驾驶，但MJ的急性使用对驾驶表现的负面影响一直难以捉摸，难以复制。大多数驾驶研究使用日光环境和干燥的道路条件。当能见度降低时在天黑后驾驶和/或在结冰/积雪的道路上驾驶可能会进一步消耗驾驶技能，从而暴露出重大的缺陷。使用这一更具挑战性但现实的情景可能会提供一种更敏感、更可重复性的驾驶损害衡量标准。在这些新颖的模拟驾驶场景中，将使用功能磁共振成像(FMRI)来阐明大麻对已知驾驶神经电路的影响。偶尔吸食大麻的人(n=24)将参与这项受试者内重复测量的设计。在随机顺序和单独的测试过程中，参与者将通过有节奏的吸入方案获得安慰剂、200 mC/kg或300 mC/kg的蒸发大麻。参与者将在四个模拟环境中驾驶：白天道路干燥，白天道路结冰，夜间道路干燥，夜间道路结冰。在正常路况下，受大麻影响的参赛者预计会出现补偿性减速。健康、未醉酒的志愿者通常在结冰和夜间的条件下都会减慢速度。我们假设，MJ参与者在次优驾驶条件下不会表现出这样的减速。我们进一步假设，大脑中富含大麻素受体并参与程序性学习的区域(例如小脑)将显示出神经连接的改变，而大麻素受体较少的区域(例如主要视觉区域)或较少参与程序性学习的区域(例如杏仁核)将保持不受影响。在未来的研究中，识别可复制的驾驶场景将有助于建立一个行为阈值，在这个阈值上，驾驶会因大麻而受损。识别大麻中毒改变的驾驶神经回路将有助于理解大麻对驾驶的影响是否主要是由于决策、知觉扭曲、运动协调或程序技能缺陷。参与决策和判断的神经回路受损将产生更严重的公共健康后果，因为受大麻影响的人可能更有可能在醉酒后继续驾驶。 与公共健康相关：尽管人们普遍认为大麻是有害的，但急性使用大麻对驾驶性能的负面影响很难在可重复的研究中记录下来。然而，大多数研究都评估了白天在干燥路况下驾驶的情况。这项研究建议，在能见度降低的天黑后驾驶和/或在结冰、湿滑的道路上驾驶，可能会为大麻影响下的驾驶损害提供更敏感、更具重复性的衡量标准。功能性核磁共振成像将进一步深入了解大麻如何损害驾驶过程中涉及的神经电路。

DESCRIPTION (provided by applicant): Despite a widespread belief that marijuana (MJ) impairs driving, the negative impact of acute MJ use on driving performance has been elusive and difficult to replicate. Most driving studies use daylight environments and dry road conditions. Driving after dark when visibility is diminished and/or on icy/snowy roads may further tax driving skills to reveal important deficits. Use of this more challenging, yet realistic scenario may provide a more sensitive, reproducible measure of driving impairment. Functional magnetic resonance imaging (fMRI) will be used during these novel simulated driving scenarios to elucidate the impact of marijuana on known driving neural circuitry. Occasional marijuana users (n=24) will participate in this within-subject, repeated measures design. In a randomized order and in separate testing sessions, participants will receive a placebo, 200 mc/kg, or 300 mc/kg vaporized marijuana via a paced inhalation protocol. Participants will drive in four simulated environments: daylight with dry roads, daylight with icy roads, nighttime with dry roads, and nighttime with icy roads. Under normal road conditions, participants under the influence of marijuana are expected to show a compensatory decrease in speed. Healthy, non-intoxicated volunteers usually slow down in both icy and nighttime conditions. We hypothesize that MJ participants will fail to show such slowing under sub-optimal driving conditions. We further hypothesize brain regions rich in cannabinoid receptors and involved in procedural learning (e.g., the cerebellum) will show altered neural connectivity, while regions with few cannabinoid receptors (e.g., primary visual area) or areas with less involvement in procedural learning (e.g., amygdala) will remain unaffected. Identification of replicable driving scenarios will be useful in future research establishing a behavioral threshold at which driving becomes impaired by marijuana. Identification of the driving neural circuitry altered by marijuana intoxication will aid in understanding whether the impact of marijuana on driving is primarily due to decision making, perceptual distortions, motor coordination, or procedural skill deficits. Impaired neural circuitry involved in decision-making and judgment will have more serious public health consequences as persons under the influence of marijuana may be more likely to continue driving despite intoxication. PUBLIC HEALTH RELEVANCE: Despite a widespread belief that it is harmful, the negative impact of acute marijuana use on driving performance has been difficult to document in repeatable research studies. Most studies, however, evaluate driving during daylight hours with dry road conditions. Driving after dark when visibility is diminished and/or on icy, slippery roads as proposed in this study may provide a more sensitive, reproducible measure of driving impairment under the influence of marijuana. Functional magnetic resonance imaging will provide further insight into how marijuana impairs the neural circuitry involved in driving.