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Effect of Cannabidiol and Δ9-Tetrahydrocannabinol on Driving PerformanceA Randomized Clinical Trial

Educational Objective
To understand the effects of cannabis on driving performance and cognition.
1 Credit CME
Key Points

Question  What is the magnitude and duration of driving impairment following vaporization of cannabis containing varying concentrations of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD)?

Findings  In this crossover clinical trial that included 26 healthy participants who underwent on-road driving tests, the standard deviation of lateral position (SDLP, a measure of lane weaving, swerving, and overcorrecting) at 40 to 100 minutes following vaporized consumption was 18.21 cm for CBD-dominant cannabis, 20.59 cm for THC-dominant cannabis, 21.09 cm for THC/CBD-equivalent cannabis, and was 18.26 cm for placebo. At 240 to 300 minutes, the SDLP was 19.03 cm for CBD-dominant cannabis, 20.59 cm for THC-dominant cannabis, 19.88 cm for THC/CBD-equivalent cannabis, and 19.37 cm for placebo. Compared with placebo, SDLP with THC-dominant and THC/CBD-equivalent cannabis was significantly greater at 40 to 100 minutes but not 240 to 300 minutes after consumption; there were no significant differences between CBD-dominant cannabis and placebo.

Meaning  Although this study did not find statistically significant differences in driving performance during experimental on-road driving tests between CBD-dominant cannabis and placebo, the effect size may not have excluded clinically important impairment, and the doses tested may not necessarily represent common usage.

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

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Article Information

Corresponding Author: Jan Ramaekers, PhD, Maastricht University, Universiteitssingel 40, Maastricht 6229 ER, the Netherlands (j.ramaekers@maastrichtuniversity.nl).

Accepted for Publication: October 9, 2020.

Author Contributions: Drs Arkell and Ramaekers had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Arkell, Theunissen, McGregor, Ramaekers.

Acquisition, analysis, or interpretation of data: Arkell, Vinckenbosch, Kevin, McGregor, Ramaekers.

Drafting of the manuscript: Arkell, Kevin, McGregor, Ramaekers.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Arkell, Kevin, Ramaekers.

Obtained funding: McGregor, Ramaekers.

Administrative, technical, or material support: Vinckenbosch, Kevin, McGregor, Ramaekers.

Supervision: Theunissen, McGregor, Ramaekers.

Conflict of Interest Disclosures: Dr Kevin reported receipt of grants from The Lambert Initiative for Cannabinoid Therapeutics during the conduct of the study; and involvement as an expert witness in legal cases involving cannabis impairment. Dr McGregor reported receipt of grants from the National Health and Medical Research Council of Australia, the Australian Research Council, and the Lambert Initiative for Cannabinoid Therapeutics during the conduct of the study; patents to WO2019071302 and WO2019227167 published, patents to WO2018107216A1, WO2017004674A1, and WO2011038451A1 issued and licensed, and patents to AU2017904438 and AU2019051284 pending; consultancy with Kinoxis Therapeutics around the development of noncannabinoid therapeutics; involvement as an expert witness in legal cases involving cannabis-induced impairment; and a speaker's honorarium from Janssen. Dr Ramaekers reported receipt of grants from Lambert Initiative for Cannabinoid Therapeutics during the conduct of the study; and being president of the International Council on Alcohol, Drugs and Traffic Safety (ICADTS). No other disclosures were reported.

Funding/Support: This study was funded by the Lambert Initiative for Cannabinoid Therapeutics at the University of Sydney.

Role of the Sponsor/Funder: The Lambert Initiative for Cannabinoid Therapeutics, a philanthropically funded independent research center at the University of Sydney, was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review and approval of the manuscript; and the decision to submit the manuscript for publication. The sponsor did not have the right to veto publication or control the decision regarding which journal the manuscript would be submitted to for publication.

Data Sharing Statement: See Supplement 3.

Additional Contributions: We are grateful to the following students from Maastricht University: Christin Büdenbender, BSc, Keziah Kusuma, BSc, Fabian Miramontes, BSc, Jacqueline Roux, BSc, and Dennis Ruesink, BSc, for their assistance with data collection. None of these individuals received compensation for their role in the study. We also wish to sincerely thank Peter Doohan, BSc (Hons), University of Sydney, for his assistance with the analysis of plasma samples. Peter Doohan received compensation for his role in the study.

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