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

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2022 · $226,952

## Abstract

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.

## Key facts

- **NIH application ID:** 10507865
- **Project number:** 1R21DA056687-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Dustin Clark Lee
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $226,952
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10507865

## Citation

> US National Institutes of Health, RePORTER application 10507865, Examining the Role of Tolerance on Dose-dependent Effects of Acute THC on Oculomotor and Cognitive Performance (1R21DA056687-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10507865. Licensed CC0.

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