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This article originally appeared at https://www.sciencedirect.com/science/article/abs/pii/S0376871615003142

Authors: Rebecca L. Hartman ab, Timothy L. Brown c, Gary Milavetz d, Andrew Spurgin d, Russell S. Pierce e, David A. Gorelick af, Gary Gaffney gMarilyn A. Huestis a

https://doi.org/10.1016/j.drugalcdep.2015.06.015Get rights and content

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 Δ9-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 500 mg placebo, low (2.9%)-THC, or high (6.7%)-THC vaporized cannabis over 10 min ad libitum in separate sessions (within-subject design, 6 conditions). Participants drove (National Advanced Driving Simulator, University of Iowa) simulated drives (∼0.8 h duration). Blood, oral fluid (OF), and breath alcohol samples were collected before (0.17 h, 0.42 h) and after (1.4 h, 2.3 h) driving that occurred 0.5–1.3 h 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 μg/L during driving increased SDLP similar to 0.05 and 0.08 g/210 L breath alcohol concentrations, the most common legal alcohol limits. Cannabis-alcohol SDLP effects were additive rather than synergistic, with 5 μg/L THC + 0.05 g/210 L alcohol showing similar SDLP to 0.08 g/210 L 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 μg/L increased SDLP similar to notably-impairing alcohol concentrations. Despite OF’s screening value, OF variability poses challenges in concentration-based effects interpretation.

Graphical abstract

Introduction

Reducing drugged driving is a U.S. and worldwide priority (ONDCP, 2013). Cannabis is the most frequently detected illicit drug in drivers (Berning et al., 2015, Lacey et al., 2009, Legrand et al., 2013, Pilkinton et al., 2013); 12.6% of weekend nighttime drivers were positive for Δ9-tetrahydrocannabinol (THC, primary psychoactive phytocannabinoid), in 2013–2014, a 48% increase since 2007 (Berning et al., 2015). Although blood THC is associated with increased crash risk and driver culpability (Asbridge et al., 2012, Drummer et al., 2004, Gjerde et al., 2011, Laumon et al., 2005, Li et al., 2012), cannabis effects on driving remain heavily debated. Road tracking and ability to remain within the lane are crucial driving skills. Lane weaving, an observable effect of drug-impaired driving, is a common measure for assessing driving performance. Standard deviation of lateral position (SDLP) is a sensitive vehicular control indicator, often employed in drugged driving research (Anderson et al., 2010, Lenné et al., 2010, Ramaekers et al., 2006a, Verster et al., 2006). In previous studies, cannabis increased SDLP and straddling lanes, but results were assessed by dose rather than blood THC concentrations (Ramaekers et al., 2000, Robbe, 1998, Downey et al., 2013).

To date, 23 states and the District of Columbia (DC) approved medical marijuana; four states and DC legalized recreational cannabis for adults (ProCon.org, 2014). Cannabis legalization is a crucial road safety issue. Since legalizing medical marijuana (2000), Colorado observed increased driving under the influence of cannabis (DUIC) cases (Urfer et al., 2014), and fatal motor vehicle crashes with cannabis-positive drivers; whereas no significant change was observed in 34 states without legalized medical marijuana (Salomonsen-Sautel et al., 2014). Establishing evidence-based per se laws for DUIC remains challenging, with varying laws across the US (Armentano, 2013, Grotenhermen et al., 2007, Lacey et al., 2010). Many are concerned that implementing concentration-based cannabis-driving legislation will unfairly target individuals not acutely intoxicated, because residual THC can be detected in blood for up to a month of sustained abstinence in chronic frequent smokers (Bergamaschi et al., 2013). Appropriate blood THC concentrations that universally reflect driving impairment remain elusive. Determining blood THC concentrations associated with lateral control impairment in occasional users would benefit forensic interpretation.

There is interest in linking driving impairment with oral fluid (OF) THC concentrations. OF is easy to collect, non-invasive, and associated with recent cannabis intake (Bosker and Huestis, 2009, Drummer, 2006, Wille et al., 2014). OF-based DUIC legislation exists in some jurisdictions (Drummer et al., 2007, Huestis et al., 2011, Van der Linden et al., 2012); however, limited simultaneous driving and OF concentration data preclude direct association with impairment.

Alcohol is the most common drug identified in drivers (Berning et al., 2015, Legrand et al., 2013). Cannabis and alcohol, frequently detected together (Legrand et al., 2013), produced greater impairing effects together than either separately (Robbe, 1998, Ronen et al., 2010), but it is unclear whether effects are additive or synergistic.

This is the first in a series of manuscripts evaluating cannabis’ effects, with and without concurrent alcohol, on driving. We present here effects, relative to THC concentrations, on drivers’ lateral control. We hypothesized cannabis and alcohol would each impair lateral control, with synergistic effects when combined.

Section snippets

Participants

Healthy adults provided written informed consent for this Institutional Review Board-approved study. Inclusion criteria were ages 21–55 years; self-reported cannabis consumption ≥1×/3 months but ≤3 days/week over the past three months (Cannabis Use Disorders Identification Test [CUDIT]; Adamson and Sellman, 2003); self-reported “light” or “moderate” alcohol consumption according to a Quantity-Frequency-Variability (QFV) scale (Sobell and Sobell, 2003); or, if “heavy”, not more than 3–4 servings

Participants

Nineteen healthy adults (13 men, ages 21–37 years, 74% white) participated (Table 1). Most consumed cannabis ≥2×/month (but ≤3 days/week), and reported last intake within a week prior to admission. Participants self-reported driving 6–23 years, and all reported driving ≥1×/week. Data review revealed one participant (#12) was consistently an extreme outlier in almost all measures and dosing conditions, including placebo cannabis/placebo alcohol. Driving videos indicated markedly erratic and

Discussion

Using a sophisticated driving simulator and rigorous placebo-controlled, within-subject design, we found a positive association between blood THC concentration and one (SDLP) of three alcohol-sensitive lateral control impairment measures (SDLP, normalized lane departures, maximum acceleration). Cannabis-alcohol combination effects were additive, not synergistic.

Decreased lateral control was associated with blood THC concentrations and BrAC, based on descriptive models. SDLP is among the most

Role of funding source

This research was funded by the United States Office of National Drug Control Policy; the Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health; and the National Highway Traffic Safety Administration. Additionally, the Institute for Clinical and Translational Science at the University of Iowa is supported by the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program, grant U54TR001013. The CTSA program is led by the

Contributors

Authors Hartman, Brown, Gorelick, Gaffney, and Huestis participated in the research design. Authors Hartman, Brown, Milavetz, Spurgin, and Gaffney participated in research conduct, under oversight from Author Huestis. Authors Hartman, Brown, Milavetz, Spurgin, Pierce, Gaffney, and Huestis participated in data analysis, under the substantial guidance of Author Pierce. Author Hartman wrote the initial draft of the manuscript, Authors Gorelick and Huestis contributed substantially to the draft

Conflicts of interest

Volcano® and Quantisal™ devices and supplies (Storz & Bickel, Tuttlingen, Germany and Immunalysis, Pomona, CA) were provided by manufacturers through Materials Transfer Agreements. No commercial entity played any role in study design and conduct, data analysis, manuscript drafting, or the decision to publish. The authors declare no personal conflicts of interest.

Acknowledgments

We thank the nurses and staff of the University of Iowa Clinical Research Unit and National Advanced Driving Simulator staff, especially Cheryl Roe, Jennifer Henderson, Rose Schmitt, and Kayla Smith, for their excellent contributions to successful completion of the study. We also thank Drs. Dereece Smither and Richard Compton, National Highway Traffic Safety Administration (NHTSA) for valuable input and Omar Ahmad for technical assistance. We acknowledge the University of Maryland, Baltimore

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