Examining the Role of Tolerance on Dose-dependent Effects of Acute THC on Oculomotor and Cognitive Performance

检查耐受性对急性 THC 对动眼神经和认知能力的剂量依赖性影响的作用

• 批准号: 10507865
• 负责人: Dustin Clark Lee
• 金额: $ 22.7万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10507865
• 关键词: Accidents; Acute; Automobile Driving; Cannabis; Chronic; Cognitive; Crossover Design; Detection; Development; Discrimination; Dose; Double-Blind Method; Drug Kinetics; Frequencies; Future; Health; Hour; Impaired cognition; Impairment; Individual; Inhalation; Machine Learning; Measures; Medical; Methodology; Oral; Outcome; Performance; Pharmaceutical Preparations; Pilot Projects; Placebo Control; Placebos; Prevalence; Procedures; Process; Psychomotor Performance; Psychotropic Drugs; Public Health; Reading; Recording of previous events; Reporting; Research; Research Personnel; Research Proposals; Risk; Role; Route; Saccades; Sensitivity and Specificity; Series; THC exposure; Task Performances; Technology; Testing; Tetrahydrocannabinol; Time; Translating; United States; Urine; Validation; Work; Workplace; age related; alcohol research; cognitive function; cognitive performance; cognitive task; driving under influence; experience; impaired driving performance; indexing; interest; marijuana use; marijuana user; mobile computing; novel strategies; oculomotor; pilot test; portability; response; sample fixation; screening; sustained attention; vehicular accident; visual tracking

PROJECT SUMMARY The prevalence of cannabis use in the United States increased substantially in the past decade, which coincides with increases in driving under the influence of cannabis and growing concerns around cannabis use in the workplace. Such findings are a public health concern because the principle psychoactive compound in cannabis, delta-9-tetrahydrocannabinol (THC), induces acute cognitive impairment that negatively impacts cognitive and psychomotor performance that translates to increased risk of workplace and motor vehicle accidents. In contrast to alcohol, research examining the impact of acute THC impairment rarely shows a direct correlation between higher THC levels and greater impairment, due in part to non-linear elimination rates and varied pharmacokinetics across routes of administration. Accurate, portable, and single-session approaches to detecting acute THC impairment are of critical need for testing in roadside, workplace, and health settings. Oculomotor assessments demonstrate promising discrimination of impairment in both acute and chronic THC exposure studies. An oculomotor index measure for detecting cannabis impairment was developed by Co- Investigators at Zxerex using machine learning and was pilot tested in an acute THC administration study. This research proposal will build on that work by comparing the impact of acute THC on domain-specific oculomotor and cognitive tasks between those with varied cannabis use histories to help elucidate the effect of tolerance and acute THC impairment on oculomotor and cognitive function. This proposed study will apply a rigorous methodological approach with systematic dose administration to evaluate the impact of acute THC on oculomotor processing and sustained attention between frequent and infrequent cannabis users to further inform development on novel approaches to THC-impairment detection. A double-blind, placebo-controlled, within-subjects crossover design will be used to examine the dose-effects of THC on oculomotor performance tasks and a sustained attention task in frequent and infrequent cannabis users. Results from the study will advance our understanding of the effect of THC and cannabis use frequency on oculomotor function and sustained attention, and will directly inform the validity of our oculomotor platform for identifying acute THC- induced impairment in frequent and infrequent users. This study will support several future studies, including additional testing of cannabis dose-response curves and routes of administration which will be critical for further understanding how THC-impairment impacts oculomotor function. In addition, results from this study will be used to inform further development and examination of a mobile platform for assessment of oculomotor function which will be key to eventual implementation of this procedure in real-world settings.

项目摘要 在过去的十年中，美国的大麻使用率大大增加， 与大麻的影响以及对大麻使用的越来越关注的驾驶的增加相吻合 在工作场所。这样的发现是公共卫生的关注 大麻，Delta-9-四氢大麻酚（THC）诱导急性认知障碍，对产生负面影响 认知和心理运动表现，这转化为工作场所和机动车的风险增加 事故。与酒精相反，研究急性THC损伤的影响的研究很少显示直接 较高的THC水平与更大损害之间的相关性，部分是由于非线性消除率和 跨管理途径的各种药代动力学。准确，便携式和单课的方法 检测急性THC损伤对于在路边，工作场所和健康环境中进行测试至关重要。 动眼评估表明急性和慢性THC中对损伤的有希望的歧视 暴露研究。通过共同开发了用于检测大麻障碍的动眼指数措施 ZXEREX的研究人员使用机器学习，并在一项急性THC管理研究中进行了试点测试。这 研究建议将通过比较急性THC对域特异性眼球运动的影响而建立在这项工作的基础上 大麻不同的人之间的认知任务使用历史来帮助阐明公差的影响 以及对眼动和认知功能的急性THC损害。这项拟议的研究将应用严格 使用系统剂量给药的方法学方法来评估急性THC的影响 动眼处理，并在频繁和频繁的大麻使用者之间持续关注 告知开发新颖的THC损伤检测方法。双盲，安慰剂对照， 受试者内部跨界设计将用于检查THC对眼动性能的剂量效应 任务和持续的大麻用户持续关注任务。研究的结果将 提高我们对使用频率和大麻频率对眼动函数的影响的理解 受到持续关注，并将直接告知我们的眼球平台的有效性，以识别急性THC- 频繁和不常见的用户诱发损害。这项研究将支持未来的一些研究，包括 大麻剂量响应曲线和给药途径的其他测试对于对 进一步了解THC障碍如何影响眼动函数。此外，这项研究的结果将 用于为进一步的开发和检查移动平台评估眼动仪 功能将是最终在现实世界设置中实现此过程的关键。