The Impact and Detection of Driving Impairments Associated With Acute Cannabis Smoking

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Randomized, Controlled Trial of Cannabis in Healthy Volunteers Evaluating Simulated Driving, Field Performance Tests and Cannabinoid Levels

Conditions
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Cannabis Intoxication

Intervention / Treatment
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* Drug: Cannabis


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized to smoke a cannabis cigarette containing placebo (.02%), 5.9% or 13.4% THC.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Cannabis<br>Subjects will smoke cannabis with placebo THC (.02%) ad libitum | Drug: Cannabis<br>* Participants will smoke a cannabis cigarette ad libitum as per their usual routine<br>* Other names: Marijuana;|
| Experimental: Cannabis with 5.9% THC<br>Subjects will smoke cannabis cigarettes with 5.9% THC ad libitum | Drug: Cannabis<br>* Participants will smoke a cannabis cigarette ad libitum as per their usual routine<br>* Other names: Marijuana;|
| Experimental: Cannabis with 13.4% THC<br>Subjects will smoke cannabis cigarettes with 13.4% THC ad libitum | Drug: Cannabis<br>* Participants will smoke a cannabis cigarette ad libitum as per their usual routine<br>* Other names: Marijuana;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Composite Drive Score (CDS) From Pre-smoking Simulation | 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 (n = 191). 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 Time 1). | Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Simulator: Standard Deviation of Lateral Position (SDLP) | This measures the standard deviation of lateral (lane) position, or the degree to which the participant swerves within the road lane on the driving simulation during the modified Surrogate Reference Task (mSuRT). The range is from .39 to 3.33. A higher score indicates worse performance. | Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking | 
| Simulator: Speed Deviation | The variability in speed during the modified Surrogate Reference Test (mSuRT). The speed is in miles per hour. Range is from .17 to 12.85. A higher score indicates worse performance. | Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking | 
| Simulator: Correct Hits on mSuRT | The number of times the participant touched the correct stimulus (circle) on the iPad, during modified Surrogate Reference Task (mSuRT). Range is from 8 to 32. A higher score is a better score. | Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking | 
| Simulator: Car Following - Coherence | Coherence is the correlation (0 to 1) between the participant and the lead car (which speeds up and slows down), representing the participant's ability to accurately speed up and slow down similarly to the lead car. Range of scores is from .01 to .97. A higher score is a better score. | Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking | 
| Simulator: Response Delay - Car Following | Time delay (in seconds) in responding to changes in the lead car's speed. Range is from -5.8 to 6.0. A higher score indicates a worse score. | Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking | 
| Simulator: Distance From Lead Car - Car Following | The outcome is distance from the lead car (in virtual feet) during the Car Following Task | Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking | 
| Tablet Assessment: Dual Attention Missed Switches | The participant follows a moving target (square) with her/his finger, and switches to following a new stimulus when it appears in the corner of the screen. Each participant was classified as to whether he/she missed any of these switches during the trial. The outcome is the proportion of participants within each group who missed at least one switch. The range is from 0 to 1. Higher indicates a worse score. | Participants assessed pre-smoking and 1 hour, 2 hours, 4 hours, and 5 hours after smoking | 
| Tablet Assessment: Lane Tracking Standard Deviation | The participant is to rotate the iPad in order to keep a round object in the center, between two lines (lanes). This measure is the standard deviation of the position of the round object during the task (in essence, how much swerving there is within the lane). The range is from 8.2 to 189.4. A higher score indicates worse performance. | Participants assessed pre-smoking and 1 hour, 2 hours, 4 hours, and 5 hours after smoking | 
| Tablet Assessment: Visual Spatial Learning Test Number Correct | Assessment of short-term memory for abstract figures. The participant is to memorize abstract figures and their locations on a 3 x 3 grid. After initial viewing (10 seconds), the figures go away for either 4, 12, or 24 seconds. The participant is then to identify which figures were in the initial viewing (from a list at the bottom of the screen), and place them at the correct location. This is the number of correctly identified figures. The range is from 0 to 12. A higher score indicates better performance. | Participants assessed pre-smoking and 1 hour, 2 hours, 4 hours, and 5 hours after smoking | 
| Tablet Assessment: Time Estimation | The participant is to estimate the amount of time that has passed while performing a secondary task. This outcome is the ratio of 1) the estimated time that has passed (seconds), divided by 2) the actual amount of time that has passed. The range is from 0.204 to 1.89. A higher score indicates a better performance. | Participants assessed pre-smoking and 1 hour, 2 hours, 4 hours, and 5 hours after smoking | 
| Tablet Assessment: Balance | While standing and keeping their feet still, this is a measure of the participant's sway, which is the total distance that the participant's body moved (in meters) from his/her initial vertical position. This was measured using an accelerometer placed on the participant's back. The range of scores is from .222 to 1.661. A higher score indicates worse performance. | Participants assessed pre-smoking and 1 hour, 2 hours, 4 hours, and 5 hours after smoking | 
| THC Concentrations: Correlation Between Blood and Oral Fluid | Spearman's correlation between THC concentrations in whole blood and oral fluid. Higher scores are better. | Approximately 15 minutes post-smoking | 
| THC Concentrations: Correlation Between Whole Blood and Breath | Spearman's correlation between THC concentrations in whole blood and breath | Approximately 15 minutes post-smoking | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Marijuana, Oral Fluid, Driving Under the Influence, Memory Impairment, Reaction Time, Time Perception, Cannabis, Whole Blood, Breath, Driving simulator