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临床试验/NCT02849587
NCT02849587已完成1 期

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

University of California, San Diego1 个研究点 分布在 1 个国家目标入组 199 人开始时间: 2017年2月24日最近更新:
适应症
干预措施
相关药物

试验速览

阶段
1 期
状态
已完成
入组人数
199
试验地点
1
主要终点
Change in Composite Drive Score (CDS) From Pre-smoking Simulation

研究概览

简要总结

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.

详细描述

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).

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Screening
盲法
Triple (Participant, Investigator, Outcomes Assessor)

盲法说明

Product will be dispensed from the Research Pharmacy. All assessors, investigators, and participants are blinded to the THC content.

入排标准

年龄范围
21 Years 至 55 Years(Adult)
性别
All
接受健康志愿者

入选标准

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

排除标准

  • 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.

研究组 & 干预措施

Placebo Cannabis

Placebo Comparator

Subjects will smoke cannabis with placebo THC (.02%) ad libitum

干预措施: Cannabis (Drug)

Cannabis with 5.9% THC

Experimental

Subjects will smoke cannabis cigarettes with 5.9% THC ad libitum

干预措施: Cannabis (Drug)

Cannabis with 13.4% THC

Experimental

Subjects will smoke cannabis cigarettes with 13.4% THC ad libitum

干预措施: Cannabis (Drug)

结局指标

主要结局

Change in Composite Drive Score (CDS) From Pre-smoking Simulation

时间窗: Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking

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).

次要结局

  • Simulator: Correct Hits on mSuRT(Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking)
  • Simulator: Standard Deviation of Lateral Position (SDLP)(Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking)
  • Simulator: Speed Deviation(Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking)
  • Simulator: Car Following - Coherence(Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking)
  • Simulator: Response Delay - Car Following(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(Participants are assessed pre-smoking, and then approximately 30m, 1h 30m, 3h 30m and 4h 30m post-smoking)
  • Tablet Assessment: Dual Attention Missed Switches(Participants assessed pre-smoking and 1 hour, 2 hours, 4 hours, and 5 hours after smoking)
  • Tablet Assessment: Visual Spatial Learning Test Number Correct(Participants assessed pre-smoking and 1 hour, 2 hours, 4 hours, and 5 hours after smoking)
  • Tablet Assessment: Time Estimation(Participants assessed pre-smoking and 1 hour, 2 hours, 4 hours, and 5 hours after smoking)
  • Tablet Assessment: Balance(Participants assessed pre-smoking and 1 hour, 2 hours, 4 hours, and 5 hours after smoking)
  • Tablet Assessment: Lane Tracking Standard Deviation(Participants assessed pre-smoking and 1 hour, 2 hours, 4 hours, and 5 hours after smoking)
  • THC Concentrations: Correlation Between Whole Blood and Breath(Approximately 15 minutes post-smoking)
  • THC Concentrations: Correlation Between Blood and Oral Fluid(Approximately 15 minutes post-smoking)

研究者

申办方类型
Other
责任方
Principal Investigator
主要研究者

Thomas D. Marcotte, PhD

Professor

University of California, San Diego

研究点 (1)

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