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，但急性MJ使用对驾驶性能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。天黑后驾驶时，能见度降低和/或在结冰/积雪的道路上可能会进一步征税驾驶技能，以揭示重要的赤字。使用这种更具挑战性的，但现实的情况下，可以提供一个更敏感的，可重复的驾驶障碍的措施。功能性磁共振成像（fMRI）将在这些新的模拟驾驶场景中使用，以阐明大麻对已知驾驶神经回路的影响。偶尔大麻使用者（n=24）将参加这个主题内，重复测量设计。在随机顺序和单独的测试阶段，参与者将通过起搏吸入方案接受安慰剂，200 mc/kg或300 mc/kg汽化大麻。参与者将在四种模拟环境中驾驶：白天干燥的道路，白天结冰的道路，夜间干燥的道路和夜间结冰的道路。在正常的道路条件下，受大麻影响的参与者预计会表现出速度的补偿性下降。健康的、未醉酒的志愿者通常在结冰和夜间条件下都会减速。我们假设MJ参与者在次优驾驶条件下不会表现出这种减速。我们进一步假设大脑区域富含大麻素受体并参与程序性学习（例如，小脑）将显示改变的神经连接，而具有很少大麻素受体的区域（例如，主要视觉区域）或较少涉及程序学习的区域（例如，杏仁核）将保持不受影响。识别可复制的驾驶场景将有助于未来的研究，建立一个行为阈值，在该阈值下，大麻会损害驾驶能力。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卫生后果，因为大麻影响下的人可能更有可能在醉酒后继续驾驶。 公共卫生相关性：尽管人们普遍认为大麻是有害的，但在可重复的研究中，很难记录急性大麻使用对驾驶性能的负面影响。然而，大多数研究都是在干燥的道路条件下评估白天的驾驶。天黑后驾驶时，能见度降低和/或在结冰，湿滑的道路上，如本研究中提出的，可能提供一个更敏感的，可重复的措施，驾驶障碍的影响下，大麻。功能性磁共振成像将进一步深入了解大麻如何损害与驾驶有关的神经回路。

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.