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Driving ImpairedPhase 1/2NCT05273658

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

A Phase 1/2 study testing Cannabis and Alcohol in people with Driving Impaired and Alcohol Intoxication, run by University of California, San Diego.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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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. Read more about this study

Who is it for?
Ages 21 to 55 yearsHealthy volunteers can take part
What is being tested?
Cannabis and Alcohol
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
No sites listed yet
Study dates
Aug 2022to Jun 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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.

About this study

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.

Read the detailed 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.

Being tested
Cannabis, Alcohol
Keywords
Cannabis, Alcohol, Driving
Medical subject headings
Alcoholic Intoxication, Driving Under the Influence, Marijuana Abuse

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CannabisDrug

    Also called Marijuana

    Participants will smoke a cannabis cigarette ad libitum as per their usual routine

  • AlcoholDrug

    Participants will ingest alcohol to achieve the target breath alcohol level

Study groups in NCT05273658
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPlacebo cannabis and placebo alcohol
Receives: Drug: Cannabis; Drug: Alcohol
Cannabis, No alcoholExperimental18.16% THC, placebo alcohol
Receives: Drug: Cannabis; Drug: Alcohol
Cannabis, Low dose alcoholExperimental18.16% THC, .07 breath alcohol concentration
Receives: Drug: Cannabis; Drug: Alcohol
Placebo cannabis, High dose alcoholExperimental<.1% THC, .10 Breath alcohol concentration
Receives: Drug: Cannabis; Drug: Alcohol
Placebo cannabis, Low dose alcoholExperimental<.1% THC, .07 breath alcohol concentration
Receives: Drug: Cannabis; Drug: Alcohol

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Participants are assessed pre-smoking/drinking, and then approximately 30 minutes, 1 hour 30 minutes, and 3 hours 30 minutes post-smoking

Secondary outcomes (4)
  1. DRE Impairment

    DRE officers' determination regarding participant impairment

    Measured: Approximately 1.5 hours and 2.5 hours after alcohol/cannabis administration

  2. Whole blood THC concentration

    Whole blood THC concentrations determine via LC-MS-MS

    Measured: Approximately 30 minutes after alcohol/cannabis administration

  3. Oral Fluid THC concentration

    Oral fluid THC concentrations determine via LC-MS-MS

    Measured: Approximately 30 minutes after alcohol/cannabis administration

  4. Breath THC concentration

    Breath THC concentrations determine via LC-MS-MS

    Measured: Approximately 30 minutes after alcohol/cannabis administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Mar 2022
  2. Study startAug 2022 (estimated)
  3. Primary completionJun 2023 (estimated)
  4. Study completionJun 2023 (estimated)

Why it stopped: Termination of funding

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Screening
Allocation
Randomised
Intervention model
Parallel groups
Model description
Participants will be randomized to smoke a cannabis cigarette containing placebo (.02%) or 18.1% THC, and consume alcohol to achieve a breath alcohol level of .07, .10, or 0.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05273658
Sponsor's protocol ID
192048
Status last verified
Sep 2023
First submitted
28 Feb 2022
Last updated
7 Sep 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 15094417
  • 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.

    PubMed 17063973
  • 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 2007 Oct 4.

    PubMed 17916224
  • 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: 10.1002/dta.1839. Epub 2015 Aug 10.

    PubMed 26257143
  • 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/s00213-010-2042-1. Epub 2010 Oct 30.

    PubMed 21049267
  • 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 Jun 23.

    PubMed 26144593
  • 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 Anal Toxicol. 2021 Sep 17;45(8):851-862. doi: 10.1093/jat/bkab078.

    PubMed 34173005
  • 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. Clin Chem Lab Med. 2020 Apr 28;58(5):673-681. doi: 10.1515/cclm-2019-0600.

    PubMed 31527291

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Cannabis and Alcohol in people with Driving Impaired and Alcohol Intoxication, run by University of California, San Diego.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 7 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Composite Drive Score (time frame: Participants are assessed pre-smoking/drinking, and then approximately 30 minutes, 1 hour 30 minutes, and 3 hours 30 minutes post-smoking). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05273658, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Sep 2023.

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