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 过去十年，美国大麻使用流行率大幅上升， 与大麻影响下驾驶的增加以及对大麻使用的日益关注相吻合 在工作场所。这些发现是一个公共卫生问题，因为主要的精神活性化合物， 大麻，δ-9-四氢大麻酚（THC），诱导急性认知障碍， 认知和心理表现，转化为工作场所和机动车的风险增加 事故为重点与酒精相反，研究急性THC损伤的影响的研究很少显示直接的影响。 较高的THC水平和较大的损害之间的相关性，部分原因是非线性消除率， 不同给药途径的药代动力学不同。准确、便携和单次会话的方法， 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是至关重要的。 视力评估显示，急性和慢性THC的损害有希望区分 暴露研究。一种用于检测大麻损伤的视力指数测量方法是由Co， Zxerex的研究人员使用机器学习，并在急性THC管理研究中进行了初步测试。这 研究建议将建立在这项工作的基础上，通过比较急性THC对特定领域眼的影响 以及具有不同大麻使用历史的人之间的认知任务，以帮助阐明耐受性的影响 以及急性THC对眼部和认知功能的损害。这项拟议的研究将采用严格的 采用系统剂量给药的方法评价急性THC对 经常和不经常使用大麻的人之间的持续关注， 为THC损伤检测新方法的开发提供信息。一项双盲、安慰剂对照、 本研究将采用受试者内交叉设计，研究THC对眼科表现的剂量效应 任务和持续的注意力任务在频繁和不频繁的大麻使用者。研究结果将 推进我们对THC和大麻使用频率对眼功能影响的理解， 持续的关注，并将直接告知我们的眼科平台识别急性THC的有效性- 在频繁和不频繁使用者中引起损害。这项研究将支持未来的几项研究，包括 对大麻剂量-反应曲线和给药途径的额外测试， 进一步了解THC损伤如何影响眼功能。此外，这项研究的结果将 用于进一步开发和检查移动的眼科评估平台 功能，这将是最终实现这一过程在现实世界中的设置的关键。