Effect of Cannabidiol and Δ<sup>9</sup>-Tetrahydrocannabinol on Driving Performance
Authors: Thomas R. Arkell, Frederick Vinckenbosch, Richard C. Kevin, Eef L. Theunissen, Iain S. McGregor, Johannes G. Ramaekers
Journal: JAMA (2020)

<h3>Importance</h3> Cannabis use has been associated with increased crash risk, but the effect of cannabidiol (CBD) on driving is unclear. <h3>Objective</h3> To determine the driving impairment caused by vaporized cannabis containing Δ<sup>9</sup>-tetrahydrocannabinol (THC) and CBD. <h3>Design, Setting, and Participants</h3> A 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. <h3>Interventions</h3> Participants 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. <h3>Main Outcomes and Measures</h3> The 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. <h3>Results</h3> Among 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];<i>P</i> &lt; .001) and THC/CBD-equivalent cannabis (+2.83 cm [95% CI, 1.28 to 4.39];<i>P</i> &lt; .001) but not CBD-dominant cannabis (−0.05 cm [95% CI, −1.49 to 1.39];<i>P</i> &gt; .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];<i>P</i> &gt; .99), THC (0.51 cm [95% CI, −1.01 to 2.02];<i>P</i> &gt; .99) or THC/CBD (1.22 cm [95% CI, −0.29 to 2.72];<i>P</i> = .20) conditions, relative to placebo. Out of 188 test drives, 16 (8.5%) were terminated due to safety concerns. <h3>Conclusions and Relevance</h3> In 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. <h3>Trial Registration</h3> EU Clinical Trials Register:2018-003945-40