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

Cannabis Intoxication Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02849587
• Other study ID #: 160641
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 24, 2017
• Est. completion date: June 17, 2019

Study information

• Verified date: December 2021
• Source: University of California, San Diego
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 199
• Est. completion date: June 17, 2019
• Est. primary completion date: June 17, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cannabis Intoxication
• Marijuana Abuse

Intervention

Drug:
• Cannabis
Participants will smoke a cannabis cigarette ad libitum as per their usual routine

Locations

Country	Name	City	State
United States	Center for Medicinal Cannabis Research, UC San Diego	San Diego	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Diego

Country where clinical trial is conducted

United States, 

References & Publications (10)

Beck O, Stephanson N, Sandqvist S, Franck J. Detection of drugs of abuse in exhaled breath from users following recovery from intoxication. J Anal Toxicol. 2012 Nov-Dec;36(9):638-46. doi: 10.1093/jat/bks079. Epub 2012 Oct 7. — View Citation

Fabritius M, Chtioui H, Battistella G, Annoni JM, Dao K, Favrat B, Fornari E, Lauer E, Maeder P, Giroud C. Comparison of cannabinoid concentrations in oral fluid and whole blood between occasional and regular cannabis smokers prior to and after smoking a cannabis joint. Anal Bioanal Chem. 2013 Dec;405(30):9791-803. doi: 10.1007/s00216-013-7412-1. Epub 2013 Nov 8. — View Citation

Hartman RL, Huestis MA. Cannabis effects on driving skills. Clin Chem. 2013 Mar;59(3):478-92. doi: 10.1373/clinchem.2012.194381. Epub 2012 Dec 7. Review. — 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, 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 — 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

Marcotte TD, Heaton RK, Wolfson T, Taylor MJ, Alhassoon O, Arfaa K, Ellis RJ, Grant I. The impact of HIV-related neuropsychological dysfunction on driving behavior. The HNRC Group. J Int Neuropsychol Soc. 1999 Nov;5(7):579-92. Erratum in: J Int Neuropsychol Soc 2000 Nov;6(7):854. — View Citation

Marcotte TD, Rosenthal TJ, Roberts E, Lampinen S, Scott JC, Allen RW, Corey-Bloom J. The contribution of cognition and spasticity to driving performance in multiple sclerosis. Arch Phys Med Rehabil. 2008 Sep;89(9):1753-8. doi: 10.1016/j.apmr.2007.12.049. — View Citation

Papafotiou K, Carter JD, Stough C. An evaluation of the sensitivity of the Standardised Field Sobriety Tests (SFSTs) to detect impairment due to marijuana intoxication. Psychopharmacology (Berl). 2005 Jun;180(1):107-14. Epub 2004 Dec 24. — View Citation

Sobolesky PM, Smith BE, Hubbard JA, Stone J, Marcotte TD, Grelotti DJ, Grant I, Fitzgerald RL. Validation of a liquid chromatography-tandem mass spectrometry method for analyzing cannabinoids in oral fluid. Clin Chim Acta. 2019 Apr;491:30-38. doi: 10.1016 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	THC Concentrations: Correlation Between Whole Blood and Breath	Spearman's correlation between THC concentrations in whole blood and breath	Approximately 15 minutes post-smoking

External Links

•   Center for Medicinal Cannabis Research, UC San Diego