• Thomas R Arkell, Frederick Vinckenbosch, Richard C Kevin, Eef L Theunissen, Iain S McGregor, and Johannes G Ramaekers.
• Lambert Initiative for Cannabinoid Therapeutics, The University of Sydney, Sydney, New South Wales, Australia.
• JAMA. 2020 Dec 1; 324 (21): 2177-2186.

ImportanceCannabis use has been associated with increased crash risk, but the effect of cannabidiol (CBD) on driving is unclear.ObjectiveTo determine the driving impairment caused by vaporized cannabis containing Δ9-tetrahydrocannabinol (THC) and CBD.Design, Setting, And ParticipantsA double-blind, within-participants, randomized clinical trial was conducted at the Faculty of Psychology and Neuroscience at Maastricht University in the Netherlands between May 20, 2019, and March 27, 2020. Participants (N = 26) were healthy occasional users of cannabis.InterventionsParticipants vaporized THC-dominant, CBD-dominant, THC/CBD-equivalent, and placebo cannabis. THC and CBD doses were 13.75 mg. Order of conditions was randomized and balanced.Main Outcomes And MeasuresThe primary end point was standard deviation of lateral position (SDLP; a measure of lane weaving) during 100 km, on-road driving tests that commenced at 40 minutes and 240 minutes after cannabis consumption. At a calibrated blood alcohol concentration (BAC) of 0.02%, SDLP was increased relative to placebo by 1.12 cm, and at a calibrated BAC of 0.05%, SDLP was increased relative to placebo by 2.4 cm.ResultsAmong 26 randomized participants (mean [SD] age, 23.2 [2.6] years; 16 women), 22 (85%) completed all 8 driving tests. At 40 to 100 minutes following consumption, the SDLP was 18.21 cm with CBD-dominant cannabis, 20.59 cm with THC-dominant cannabis, 21.09 cm with THC/CBD-equivalent cannabis, and 18.28 cm with placebo cannabis. SDLP was significantly increased by THC-dominant cannabis (+2.33 cm [95% CI, 0.80 to 3.86]; P < .001) and THC/CBD-equivalent cannabis (+2.83 cm [95% CI, 1.28 to 4.39]; P < .001) but not CBD-dominant cannabis (-0.05 cm [95% CI, -1.49 to 1.39]; P > .99), relative to placebo. At 240 to 300 minutes following consumption, the SDLP was 19.03 cm with CBD-dominant cannabis, 19.88 cm with THC-dominant cannabis, 20.59 cm with THC/CBD-equivalent cannabis, and 19.37 cm with placebo cannabis. The SDLP did not differ significantly in the CBD (-0.34 cm [95% CI, -1.77 to 1.10]; P > .99), THC (0.51 cm [95% CI, -1.01 to 2.02]; P > .99) or THC/CBD (1.22 cm [95% CI, -0.29 to 2.72]; P = .20) conditions, relative to placebo. Out of 188 test drives, 16 (8.5%) were terminated due to safety concerns.Conclusions And RelevanceIn a crossover clinical trial that assessed driving performance during on-road driving tests, the SDLP following vaporized THC-dominant and THC/CBD-equivalent cannabis compared with placebo was significantly greater at 40 to 100 minutes but not 240 to 300 minutes after vaporization; there were no significant differences between CBD-dominant cannabis and placebo. However, the effect size for CBD-dominant cannabis may not have excluded clinically important impairment, and the doses tested may not represent common usage.Trial RegistrationEU Clinical Trials Register: 2018-003945-40.

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