Effects of Cannabis/Alcohol on Driving Performance and Field Sobriety Tests

Alcohol Intoxication Clinical Trial

Official title:

Effects of Cannabis/Alcohol on Driving Performance and Field Sobriety Tests

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT05273658
• Other study ID #: 192048
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: August 2022
• Est. completion date: June 2023

Study information

• Verified date: September 2023
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The overarching aim of this study is to examine the impact of acute cannabis and alcohol administration on driving performance, as well as identify methods for detecting driving under the influence of these substances. One-hundred twenty-five healthy volunteers will be randomized into one of 5 conditions; those who receive 1) low dose alcohol and placebo cannabis, 2) low dose alcohol and tetrahydrocannabinol (THC), 3) high dose alcohol and placebo cannabis, 4) placebo alcohol and THC, and 5) double placebo. Cannabis inhaled ad libitum and/or ingested alcohol will take place at the beginning of the day followed by the completion of driving simulations, components of the Drug Recognition Expert (DRE) evaluations, and bodily fluid draws (e.g., blood, oral fluid/saliva, breath) over the subsequent 4 hours after ingestion. The purpose of this study is to determine (1) the impact of Δ9-THC on driving performance with and without concurrent alcohol ingestion (2) the duration of driving impairment in terms of hours from initial use, (3) the relationship between performance on the DRE measures and cannabis/alcohol ingestion, and 4) if saliva or expired air can serve as a useful adjunct to the field for blood sampling.

Description:

Driving under the influence of alcohol and cannabis presents significant safety risks. In the real world, impairment is usually determined via the standardized field sobriety tests (SFSTs), a series of psychophysiological tests conducted by law enforcement officers. These include the Horizontal Gaze Nystagmus (HGN; eye movements when following the officer's fingers in space), Walk and Turn (WAT; walking nine steps, turning, and walking back), and One Leg Stand (OLS; holding each leg in the air for a designated period of time).

Despite a vast literature documenting impaired driving behavior due to alcohol consumption, much less is known regarding driving under the influence of cannabis, and even less about how the combination of alcohol and cannabis may affect driving behavior. This study will examine whether either, or both, conditions significantly impact performance in a driving simulator, on cognitive measures, and during the comprehensive Drug Recognition Expert evaluations (which includes SFSTs, as well as additional measures).

Alcohol studies. Higher blood alcohol levels (BACs) have been consistently related to impaired driving. BACs greater than .08% have been associated with 5.5 times higher crash risk compared to those without alcohol or drugs. In terms of detecting alcohol-related impairment, SFSTs have consistently been shown to be predictors of a blood alcohol concentration of .08%.

Cannabis studies. Several studies suggest higher doses of whole-blood or plasma delta-9 tetrahydrocannabinol (THC) concentration are associated with increased crash risk and crash culpability. However, attempts to define a cut-off point for blood THC levels have proven to be challenging. Unlike alcohol, for which a level can be reasonably measured using a breathalyzer (and confirmed with a blood test), detection of a cut-off point for intoxication related to THC concentration has eluded scientific verification. Most recently, we did not find any correlation between blood THC concentrations and driving performance. To date, the relationship between SFSTs and cannabis use/impairment have been mixed across studies.

Cannabis and Alcohol. There have been a limited number of studies examining the combination of cannabis and alcohol on driving and/or field sobriety test performance.

With respect to subjective effects, alcohol has been found to potentiate the duration of the cannabis effects, with subjective effects being longer in the cannabis-alcohol combinations compared to either drug alone. Participants also reported more effects after alcohol and cannabis were combined, compared to alcohol alone. Another study found that alcohol pre-treatment decreased the latency to the cannabis effects, and increased the duration of the effects. It has also been hypothesized that frequent cannabis users may develop cross-tolerance to the effects of alcohol.

Some studies have found SFSTs to be only mildly sensitive to cannabis effects in heavy cannabis users, but sensitive to doses of alcohol.

There have also been suggestions that the concurrent presence of cannabis and alcohol may result in increased THC and 11-Hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) levels, possibly by affecting initial absorption (resulting in higher concentrations immediately post-inhalation; the overall area under the curve (AUC) does not differ based upon alcohol ingestion), although the possible mechanisms for this - such as increased cardiac output facilitating absorption via increased pulmonary capillary flow, or less cannabis self-titration after alcohol intake - are as yet unresolved.

Research Design

One-hundred twenty-five healthy volunteers will be randomized into one of 5 conditions; those who receive 1) low dose alcohol and placebo cannabis, 2) low dose alcohol and THC, 3) high dose alcohol and placebo cannabis, 4) placebo alcohol and THC, and 5) double placebo.

Cannabis, acquired from the National Institute on Drug Abuse Drug Supply Program, will be inhaled ad libitum and/or ingested alcohol will take place at the beginning of the day followed by the completion of driving simulations, components of the Drug Recognition Expert (DRE) evaluations, and bodily fluid draws (e.g., blood, oral fluid [OF] saliva, breath) over the subsequent 4 hours after ingestion.

Driving simulations will be conducted using a 3-monitor, fully-interactive STISIM (Systems Technology Inc. Simulator) console system. The simulations will be similar to those used in our recently completed study of 191 cannabis users.

Drug Recognition Expert (DRE) evaluations will be conducted by DREs, and will consist of 1) Preliminary Examination and First Pulse; 2) Eye Examinations: Horizontal gaze nystagmus (HGN); Vertical gaze nystagmus (VGN); Lack of convergence (LOC); 3) Divided Attention Psychophysical Tests: Modified Romberg balance; Walk and turn; One leg stand; Finger to nose; 4) Vital Signs and Second Pulse (Blood pressure, temperature, pulse); 5) Dark Room Examinations (pupillometer): Assess for dilation or constriction; pupillary response to light; 6) Examination for Muscle Tone; 7) Third Pulse.

Cannabinoids levels in blood, oral fluid, and breath will be determined via liquid chromatography with tandem mass spectrometry (LC-MS-MS).

The results of this study will further advance the understanding of the impact of acute cannabis and alcohol administration on driving performance, as well as the best methods for detecting driving under the influence of these substances.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: June 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 55 Years

Eligibility

Inclusion Criteria:

• Aged 21 to 55

• Must be a licensed driver and driven a minimum of 1,000 miles in the past year

• Experience with cannabis and alcohol

Exclusion Criteria:

• At the discretion of the examining physician, individuals with significant cardiovascular, hepatic or renal disease, uncontrolled hypertension, and chronic pulmonary disease (eg, asthma, COPD) will be excluded.

• Unwillingness to abstain from cannabis for 2 days prior to screening and experimental visits

• Positive pregnancy test

• A positive result on toxicity screening for cocaine, amphetamines, opiates, and phencyclidine (PCP) will exclude individuals from participation.

• Unwilling to refrain from driving or operating heavy machinery after consuming study medication.

Related Conditions & MeSH terms

• Alcohol Intoxication
• Alcoholic Intoxication
• Cannabis Intoxication
• Driving Impaired
• Driving Under the Influence
• Marijuana Abuse

Intervention

Drug:
• Cannabis
Participants will smoke a cannabis cigarette ad libitum as per their usual routine
• Alcohol
Participants will ingest alcohol to achieve the target breath alcohol level

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

References & Publications (8)

Grotenhermen F, Leson G, Berghaus G, Drummer OH, Kruger HP, Longo M, Moskowitz H, Perrine B, Ramaekers JG, Smiley A, Tunbridge R. Developing limits for driving under cannabis. Addiction. 2007 Dec;102(12):1910-7. doi: 10.1111/j.1360-0443.2007.02009.x. Epub — View Citation

Hartman RL, Brown TL, Milavetz G, Spurgin A, Gorelick DA, Gaffney G, Huestis MA. Controlled vaporized cannabis, with and without alcohol: subjective effects and oral fluid-blood cannabinoid relationships. Drug Test Anal. 2016 Jul;8(7):690-701. doi: 10.100 — View Citation

Hartman RL, Brown TL, Milavetz G, Spurgin A, Pierce RS, Gorelick DA, Gaffney G, Huestis MA. Cannabis effects on driving lateral control with and without alcohol. Drug Alcohol Depend. 2015 Sep 1;154:25-37. doi: 10.1016/j.drugalcdep.2015.06.015. Epub 2015 J — View Citation

Hoffman MA, Hubbard JA, Sobolesky PM, Smith BE, Suhandynata RT, Sanford S, Sones EG, Ellis S, Umlauf A, Huestis MA, Grelotti DJ, Grant I, Marcotte TD, Fitzgerald RL. Blood and Oral Fluid Cannabinoid Profiles of Frequent and Occasional Cannabis Smokers. J — View Citation

Hubbard JA, Smith BE, Sobolesky PM, Kim S, Hoffman MA, Stone J, Huestis MA, Grelotti DJ, Grant I, Marcotte TD, Fitzgerald RL. Validation of a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to detect cannabinoids in whole blood and breath — View Citation

Movig KL, Mathijssen MP, Nagel PH, van Egmond T, de Gier JJ, Leufkens HG, Egberts AC. Psychoactive substance use and the risk of motor vehicle accidents. Accid Anal Prev. 2004 Jul;36(4):631-6. doi: 10.1016/S0001-4575(03)00084-8. — View Citation

Ramaekers JG, Theunissen EL, de Brouwer M, Toennes SW, Moeller MR, Kauert G. Tolerance and cross-tolerance to neurocognitive effects of THC and alcohol in heavy cannabis users. Psychopharmacology (Berl). 2011 Mar;214(2):391-401. doi: 10.1007/s00213-010-20 — View Citation

Stuster J. Validation of the standardized field sobriety test battery at 0.08% blood alcohol concentration. Hum Factors. 2006 Fall;48(3):608-14. doi: 10.1518/001872006778606895. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite Drive Score	The Composite Drive Score (CDS) is a z-score comprised of key variables from the simulator tasks (SDLP, speed deviation, and task accuracy during the modified Surrogate Reference Task (mSuRT); coherence from the car following task). This outcome reflects the change in CDS from the pre-smoking assessment, at each timepoint.; The z-score indicates the number of standard deviations away from the mean from the baseline performance for the entire group. A Z-score of 0 is equal to the mean of a reference population (in this case the pre-smoking performance for the entire group).; Higher z-scores at each timepoint indicate worse performance (variables that went in the opposite direction were reflected in order to have all variables have the same direction). When examining the change in Composite Drive Score (this outcome variable), a higher score indicates a decline in performance (e.g., Time 2 minus Time1).	Participants are assessed pre-smoking/drinking, and then approximately 30 minutes, 1 hour 30 minutes, and 3 hours 30 minutes post-smoking
Secondary	DRE Impairment	DRE officers' determination regarding participant impairment	Approximately 1.5 hours and 2.5 hours after alcohol/cannabis administration
Secondary	Whole blood THC concentration	Whole blood THC concentrations determine via LC-MS-MS	Approximately 30 minutes after alcohol/cannabis administration
Secondary	Oral Fluid THC concentration	Oral fluid THC concentrations determine via LC-MS-MS	Approximately 30 minutes after alcohol/cannabis administration
Secondary	Breath THC concentration	Breath THC concentrations determine via LC-MS-MS	Approximately 30 minutes after alcohol/cannabis administration