ABSTRACT: BACKGROUND:Effects of cannabis, the most commonly encountered non-alcohol drug in driving under the influence cases, are heavily debated. We aim to determine how blood ?(9)-tetrahydrocannabinol (THC) concentrations relate to driving impairment, with and without alcohol. METHODS:Current occasional (?1×/last 3 months, ?3days/week) cannabis smokers drank placebo or low-dose alcohol, and inhaled 500mg placebo, low (2.9%)-THC, or high (6.7%)-THC vaporized cannabis over 10min ad libitum in separate sessions (within-subject design, 6 conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives (?0.8h duration). Blood, oral fluid (OF), and breath alcohol samples were collected before (0.17h, 0.42h) and after (1.4h, 2.3h) driving that occurred 0.5-1.3h after inhalation. We evaluated standard deviations of lateral position (lane weave, SDLP) and steering angle, lane departures/min, and maximum lateral acceleration. RESULTS:In N=18 completers (13 men, ages 21-37years), cannabis and alcohol increased SDLP. Blood THC concentrations of 8.2 and 13.1?g/L during driving increased SDLP similar to 0.05 and 0.08g/210L breath alcohol concentrations, the most common legal alcohol limits. Cannabis-alcohol SDLP effects were additive rather than synergistic, with 5?g/L THC+0.05g/210L alcohol showing similar SDLP to 0.08g/210L alcohol alone. Only alcohol increased lateral acceleration and the less-sensitive lane departures/min parameters. OF effectively documented cannabis exposure, although with greater THC concentration variability than paired blood samples. CONCLUSIONS:SDLP was a sensitive cannabis-related lateral control impairment measure. During drive blood THC ?8.2?g/L increased SDLP similar to notably-impairing alcohol concentrations. Despite OF's screening value, OF variability poses challenges in concentration-based effects interpretation.