PROJECT SUMMARY Cannabidiol (CBD) is now a legal, widely consumed, substance in the United States, but research regarding CBD’s effects in healthy populations remains sparse. Although findings of studies conducted in both healthy and clinical populations suggest that CBD may produce sedative effects, conclusions have been hampered by small sample sizes and other methodological limitations. Given that sedation and drowsiness could ultimately impair driving performance and increase drivers’ risk of motor vehicle collision, understanding the effects of non-prescription CBD on driving performance and cognitive function in non-clinical populations is paramount. However, only 3 studies involving 83 adults worldwide, have investigated CBD’s effects on driving performance and each have methodological limitations. To close this research gap, a 5-year project is proposed to further our understanding of whether and how CBD may impact driving performance by dose and biological sex in a sample of young healthy adults using a driving simulator and a battery of well-validated self-report instruments and cognitive tests. Our long-term goal is to definitively determine the effects of CBD on driving performance and motor vehicle collision risk among all drivers. The specific aims of this project are 1) determine the effects of CBD on the driving performance of healthy adults aged 18-30 years by dose and biological sex, 2) determine the effects of CBD on participants’ drowsiness, sedation, and cognitive function by dose and biological sex, and 3) determine whether changes in participants’ drowsiness, sedation, and cognitive function are associated with driving performance. The research strategy will involve a randomized, parallel-group, double-blind, sex-stratified, three-arm trial. Three hundred participants will be randomized to receive either: (1) 300 mg of pure CBD oil (N=100), (2) 150 mg of CBD oil (N=100) or (3) placebo oil (N=100) matched in appearance and taste. After baseline cognitive testing, treatment consumption, and a 120-minute wait period, each individual will then participate in a 40-minute driving simulation and re-take the cognitive tests. Our central hypothesis is that, relative to placebo, increasing doses of CBD will be associated with greater impairment in driving performance, as well as increased drowsiness and sedation, and a decline in cognitive function. We also anticipate greater impairment in these outcomes among males vs. females based on our pilot study results. Given that CBD products are growing in popularity at an exponential rate, and their effects in a healthy population are virtually unknown, the potential impact of this study is the collection of essential data regarding the unintended consequences of CBD, which may be unknowingly endangering the public by impairing drivers and increasing collision risk. This aligns with the National Institutes of Health’s mission which is to, “foster fundamental creative discoveries, innovative research strategies, and their applications as a basis for ultimately protecting and improving health.”

PROJECT NARRATIVE There is evidence that orally ingested cannabidiol, the non-psychoactive component of cannabis, has sedative- like effects, which could negatively impact driving performance, but limited research exists. The objective of this application is further our understanding of whether and how CBD may impact driving performance by dose and biological sex in a sample of young healthy adults using a driving simulator and a battery of well- validated self-report instruments and cognitive tests. Given that cannabidiol products are growing in popularity among all age groups in the United States, and their effects in a healthy population are virtually unknown, the positive impact of this study is the collection of essential data regarding the potential unintended consequences of this drug, which could put drivers and other road users at increased risk of motor vehicle collision.