Clinical trial NCT02849587: The Impact and Detection of Driving Impairments Associated With Acute Cannabis Smoking
Official title: A Randomized, Controlled Trial of Cannabis in Healthy Volunteers Evaluating Simulated Driving, Field Performance Tests and Cannabinoid Levels
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cannabis Intoxication
Keywords: Driving Under the Influence
Memory Impairment
Reaction Time
Time Perception
Cannabis
Marijuana
Whole Blood
Oral Fluid
Breath
Driving simulator
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2016-07-29
Enrollment: 199
Sex: ALL
Minimum age (years): 21
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to smoke a cannabis cigarette containing placebo (.02%), 5.9% or 13.4% THC.
Primary purpose: SCREENING

Brief summary: This study was authorized by the California Legislature (Assembly Bill 266, the Medical Marijuana Regulation and Safety Act to help with detection of driving under the influence of cannabis. One hundred and eighty healthy volunteers will inhale smoked cannabis with either 0% (placebo), 5.9%, or 13.4% Δ9-tetrahydrocannabinol (THC) at the beginning of the day, and then complete driving simulations, iPad-based performance assessments, and bodily fluid draws (e.g., blood, saliva, breath) before the cannabis smoking and a number of times over the subsequent 6 hours after cannabis smoking. The purpose is to determine (1) the relationship of the dose of Δ9-THC on driving performance and (2) the duration of driving impairment in terms of hours from initial use, (3) if saliva or expired air can serve as a useful substitute for blood sampling of Δ9-THC, and (4) if testing using an iPad can serve as a useful adjunct to the standardized field sobriety test in identifying acute impairment from cannabis.

Detailed description: There are several studies that suggest higher doses of whole-blood Δ9-tetrahydrocannabinol (Δ9-THC) concentration are associated with increased crash risk and crash culpability. However, attempts to define a cut-off point for blood Δ9-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 Δ9-THC concentration has eluded scientific verification. Recent evidence suggests blood Δ9-THC concentrations of 2-5 ng/mL are associated with substantial driving impairment, particularly in occasional smokers. Others have countered that this level leads to false positives, particularly in heavy cannabis users inasmuch as THC may be detectable in their blood specimens for 12-24 hours after inhalation. Given that 12 to 24 hours is beyond the likely period of driving impairment, this would appear to be a justifiable objection to a per se cut-off point for a Δ9-THC concentration indicative of impairment. Maximal driving impairment is found 20 to 40 minutes after smoking, and the risk of driving impairment decreases over the following hours, at least in those who smoke 18 mg Δ9-THC or less, the dose often used experimentally to duplicate a single joint. Other studies, however, report residual motor vehicle accident crash risk when cannabis is used within 4 hours prior to driving.

The roadside examination using the Standardized Field Sobriety Test (SFST) for proof of cannabis-related impairment has not been an ideal alternative to blood levels. Originally devised to evaluate impairment under the influence of alcohol, the SFST is comprised of three examinations administered in a standardized manner by law enforcement officers. The 'Horizontal Gaze Nystagmus' (HGN), the 'One Leg Stand' (OLS) and the 'Walk and Turn' test (WAT) require a person to follow instructions and perform motor activities. During the assessments, officers observe and record signs of impairment. In one study, Δ9-THC produced impairments on overall SFST performance in 50 % of the participants. In a separate study involving acute administration of cannabis, 30% of people failed the SFST. This discrepancy was thought to be in part due to the participant's cannabis use history, as well as low percentage of THC in the cannabis. The reported frequency of cannabis use varied from once a week to once every 2-6 months in the study where there was a failure on the SFST by 50% of the participants. The other study included more frequent users who smoked cannabis on at least four occasions per week.

Based upon the above, another means is needed to help law enforcement officers discern driving under the influence of cannabis. One future possibility is the development of performance-based measures of cannabis-related impairments. This will include testing of critical tracking, time estimation, balance and visual spatial learning. The investigators have selected brief measures in order to be practicably administered repeatedly over a short time period, as well as tests that have the potential to translate to a field-feasible tablet-based format, should there be benefit in possibly including these in future performance-based measures for use in the field by law enforcement officers (e.g., a cannabis-focused field sobriety test).

Eligibility criteria: Inclusion Criteria:

* Be a licensed driver.
* Need to have acuity of 20/40 or better, with or without correction on a Snellen Visual Acuity eye chart.

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 for four hours after consuming study medication.

Primary outcomes:
measure: Change in Composite Drive Score (CDS) From Pre-smoking Simulation
timeFrame: Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking
Secondary outcomes:
measure: Simulator: Standard Deviation of Lateral Position (SDLP)
timeFrame: Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking
measure: Simulator: Speed Deviation
timeFrame: Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking
measure: Simulator: Correct Hits on mSuRT
timeFrame: Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking
measure: Simulator: Car Following - Coherence
timeFrame: Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking
measure: Simulator: Response Delay - Car Following
timeFrame: Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking
measure: Simulator: Distance From Lead Car - Car Following
timeFrame: Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking
measure: Tablet Assessment: Dual Attention Missed Switches
timeFrame: Participants assessed pre-smoking and 1 hour, 2 hours, 4 hours, and 5 hours after smoking
measure: Tablet Assessment: Lane Tracking Standard Deviation
timeFrame: Participants assessed pre-smoking and 1 hour, 2 hours, 4 hours, and 5 hours after smoking
measure: Tablet Assessment: Visual Spatial Learning Test Number Correct
timeFrame: Participants assessed pre-smoking and 1 hour, 2 hours, 4 hours, and 5 hours after smoking
measure: Tablet Assessment: Time Estimation
timeFrame: Participants assessed pre-smoking and 1 hour, 2 hours, 4 hours, and 5 hours after smoking
measure: Tablet Assessment: Balance
timeFrame: Participants assessed pre-smoking and 1 hour, 2 hours, 4 hours, and 5 hours after smoking
measure: THC Concentrations: Correlation Between Blood and Oral Fluid
timeFrame: Approximately 15 minutes post-smoking
measure: THC Concentrations: Correlation Between Whole Blood and Breath
timeFrame: Approximately 15 minutes post-smoking
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Center for Medicinal Cannabis Research, UC San Diego
state: California
Study officials:
affiliation: University of California, San Diego
name: Thomas D Marcotte, PhD
role: PRINCIPAL_INVESTIGATOR
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citation: Hubbard JA, Hoffman MA, Ellis SE, Sobolesky PM, Smith BE, Suhandynata RT, Sones EG, Sanford SK, Umlauf A, Huestis MA, Grelotti DJ, Grant I, Marcotte TD, Fitzgerald RL. Biomarkers of Recent Cannabis Use in Blood, Oral Fluid and Breath. J Anal Toxicol. 2021 Sep 17;45(8):820-828. doi: 10.1093/jat/bkab080.
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 Anal Toxicol. 2021 Sep 17;45(8):851-862. doi: 10.1093/jat/bkab078.
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. Clin Chem Lab Med. 2020 Apr 28;58(5):673-681. doi: 10.1515/cclm-2019-0600.
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citation: Marcotte TD, Umlauf A, Grelotti DJ, Sones EG, Sobolesky PM, Smith BE, Hoffman MA, Hubbard JA, Severson J, Huestis MA, Grant I, Fitzgerald RL. Driving Performance and Cannabis Users' Perception of Safety: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Mar 1;79(3):201-209. doi: 10.1001/jamapsychiatry.2021.4037.