Validation of the Drug Impaired Driving Scenario (DIDS) on the CRCDS-miniSim
Condition: Driving Behavior; Driving Under the Influence
Study type: Interventional
Phase: Phase 1

Summary: 
      Subjects will participate in a 4-visit study protocol at the National Advanced Driving
      Simulator, part of the University of Iowa, in which they will be asked to complete assorted
      questionnaires, computerized cognitive tasks, and a simulator drive. Subjects will be
      administered 0.75 mg alprazolam (Xanax) or placebo and 500 mg vaporized cannabis (6.18% THC /
      <0.025% CBD) or placebo (0% THC / 0% CBD).

      The primary objective of this study is to validate the Drug Impaired Driving Scenario (DIDS)
      using the CRCDS-2 driving simulator by assessing the acute effects of cannabis relative to
      placebo on simulated driving performance. Assay sensitivity will be demonstrated by the
      significant effect of 0.75 mg alprazolam (active comparator) on driving and cognitive
      endpoints.
    

Detailed description: 
      At the University of Iowa's National Advanced Driving Simulator (NADS), normal healthy
      subjects who currently use cannabis recreationally (at least once a month) will be recruited.
      The study involves four visits, the first of which is a screening visit of approximately 3
      hours. At the screening visit, consent is obtained, questionnaires are given, and a physical
      and psychological exam is administered. Subjects will also train on study procedures, such as
      the cognitive testing, the simulator drive, and the cannabis inhalation procedure. Subjects
      will then be scheduled for their three treatment visits, which will be one week apart..

      The treatment visits will have a clean (double placebo) and two treatment visits (active
      alprazolam and placebo cannabis, placebo alprazolam and active cannabis). The alprazolam dose
      is 0.75 mg and the cannabis dose is 500 mg. All cannabis will be inhaled via a Volcano® Digit
      vaporizer using the Foltin Puff Procedure. Each of the treatment visits will last
      approximately twenty-three hours and will include intake with eligibility and baseline
      testing, transport to a local hotel, an overnight stay at the hotel, transport to NADS, being
      dosed with study drugs or placebos, cognitive assessments, a simulator drive, and assorted
      questionnaires. There will also be 8 mL blood sampling before dosing, before driving, and
      after driving. Each randomized subject will complete a treatment visit of each type one week
      apart in a counterbalanced sequence.

      Meals will be provided at the treatment visits (dinner, snack, breakfast, lunch). Subjects
      will be monitored until the drug effects have subsided sufficiently to ensure it is safe to
      transport them home. Subjects will need to arrange their own transportation; they will not be
      permitted to drive themselves home after the treatment visits.
    

Intervention name(s): Placebo (Lactose) Capsule; 0.75 mg Alprazolam Capsule; Cannabis (6.18% THC / <0.025% CBD); Cannabis (0%/ THC / 0% CBD)
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Single dose on two of the three study visits, orally administered 40 minutes prior to cannabis dose; Single dose on one of the three study visits, orally administered 40 minutes prior to cannabis dose; Cannabis vapor is produced from 500 mg of dried plant material (6.18% THC / <0.025% CBD). Subjects will inhale using the Foltin Puff Procedure over 10 minutes. Single inflated bag/dose consumed via inhalation 40 minutes after alprazolam dose on one of the three study visits.; Cannabis vapor is produced from 500 mg of dried plant material (0% THC / 0% CBD). Subjects will inhale using the Foltin Puff Procedure over 10 minutes. Single inflated bag/dose consumed via inhalation 40 minutes after alprazolam dose at two of the three study visits.
Other intervention name(s): Placebo; Placebo Alprazolam; Xanax; Active Alprazolam; Active Xanax; Marijuana; Marihuana; Active Cannabis; Marijuana; Marihuana; Placebo Cannabis; Placebo
Intervention MeSH terms: Alprazolam
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: The study uses two treatments - alprazolam and cannabis - and placebo. Subjects are randomized to a study sequence where the order of treatments (study arm) is counter-balanced, but all treatments and placebo are received by all subjects. At a visit, you might receive placebo alprazolam and placebo cannabis, placebo alprazolam and active cannabis, or active alprazolam and placebo cannabis. There is not a visit where you receive both active alprazolam and active cannabis.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Driving; Cannabis; Xanax; Marijuana; Alprazolam; Driving Impairment; Substance Use; SDLP; CogScreen; CRCDS