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

点击翻译按钮获取中文摘要

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.