Effect of Cannabidiol and Δ9-Tetrahydrocannabinol on Driving Performance: A Randomized Clinical Trial

Abstract

Importance: Cannabis use has been associated with increased crash risk, but the effect of cannabidiol (CBD) on driving is unclear.

Objective: To determine the driving impairment caused by vaporized cannabis containing Δ9-tetrahydrocannabinol (THC) and CBD.

Design, setting, and participants: 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.

Interventions: 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.

Main outcomes and measures: 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.

Results: 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]; 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 relevance: 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.

Trial registration: EU Clinical Trials Register: 2018-003945-40.

Figure 1.. Flow of Participants Through the Study of the Effects of CBD and THC on Driving Performance

CBD indicates cannabidiol condition; COVID-19, coronavirus disease 2019; THC, Δ⁹-tetrahydrocannabinol condition; THC/CBD, Δ⁹-tetrahydrocannabinol/cannabidiol condition. ^aSafety concerns regarded driving under the influence of cannabis. ^bOther reasons: 6 participants became unresponsive and could not be contacted, 3 were unable to meet study time commitments, and 1 underwent a medical screening that revealed a low red blood cell count.

Figure 2.. The Standard Deviation of Lateral Position During On-Road Driving Tests

The x-axes indicate minutes postvaporization. Higher values on the y-axes indicate more weaving vs less weaving for lower values. A, The horizontal black bars indicate the mean standard deviation of lateral position (SDLP) in each condition. B, The dashed lines indicate the mean SDLP increase associated with a blood alcohol level (BAC) of 0.02% and 0.05%. The plus symbol shows the mean change in SDLP in each condition. CBD indicates cannabidiol; THC, Δ⁹-tetrahydrocannabinol.

Figure 3.. Confidence in Driving Ability Over Time and Perceived Driving Impairment at 2 Time Points

A, Baseline on the x-axis indicates predrug administration, minute 0 indicates the end of drug administration, all other values indicate time since vaporization. The visual analog scale (VAS) indicates mean values (range, 0-10 [not confident to very confident]). B, The VAS indicates mean values (range, 0-10 [less impaired to more impaired]) as assessed at the end of each on-road driving test. Boxplot edges indicate the 25th and 75th quartile values. Horizontal bars indicate the median, and the plus signs indicate the mean. If there are no outliers (Q1 − 1.5 × [Q3 − Q1] and Q3 + 1.5 × [Q3 − Q1]), the whiskers indicate minimum and maximum values. Outliers (if present) are shown as colored symbols, the whiskers indicate the lowest and highest values that are not outliers. CBD indicates cannabidiol; THC, Δ⁹-tetrahydrocannabinol.

Figure 4.. Performance on the Digit Symbol Substitution Task, Divided Attention Task, and Paced Serial Addition Task

Time points on the x-axis indicate time since vaporization. Boxplot edges indicate the 25th and 75th quartile values. Horizontal bars indicate the median, and the plus signs indicate the mean. If there are no outliers (Q1 − 1.5 × [Q3 − Q1] and Q3 + 1.5 × [Q3 − Q1]), the whiskers indicate minimum and maximum values. Outliers (if present) are shown as colored symbols, the whiskers indicate the lowest and highest values that are not outliers. CBD indicates cannabidiol; THC, Δ⁹-tetrahydrocannabinol. Additional outcome measures are shown in eFigure 2 in Supplement 2.