Validation of the Drug Impaired Driving Scenario (DIDS) on the CRCDS-miniSim
Condition: Driving Behavior; Driving Under the Influence
Intervention: Placebo (Lactose) Capsule; 0.75 mg Alprazolam Capsule; Cannabis (6.18% THC / <0.025% CBD); Cannabis (0%/ THC / 0% CBD)
Intervention description: 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.
Intervention MeSH terms: Alprazolam
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
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)
Masking description: Study Site/National Advanced Driving Simulator: Triple (Participant, Investigator, Outcomes Assessor) blind
Enrollment: 13.0
Sex: All
Minimum age: 19 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Driving; Cannabis; Xanax; Marijuana; Alprazolam; Driving Impairment; Substance Use; SDLP; CogScreen; CRCDS

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Understands and provides written informed consent prior to the initiation of any
             protocol-specific procedures.

          -  Able to comprehend and willing to comply with the requirements of the protocol.

          -  Healthy male or female adult, 19 to 45 years of age, inclusive, at Screening.

          -  Regular sleep pattern (usual bedtime between 21:00 and 00:00).

          -  Score <10 on Epworth Sleepiness Scale at Screening.

          -  Able to reliably perform study assessments at Screening (On practice scenario, SDLP no
             higher than 1 standard deviation greater than the mean for normal healthy adults
             completing the practice scenario and subject has 7 or more correct hits on the Divided
             Attention task; CogScreen SDC Correct no less than 1 standard deviation below the mean
             for healthy adults); demonstrates the ability to understand task instructions at
             Screening; and is physically (e.g., adequate manual dexterity, vision, and hearing)
             and cognitively capable of performing study tasks at Screening.

          -  Possesses (and is willing to provide) a valid driver's license and is an active
             driver.

          -  Determined to be (by self-report) an active cannabis user with use of at least once
             per month over the preceding 90 days.

          -  Willing to abstain from cannabis use (other than study drug) beginning at the end of
             Screening until discharge from NADS on Day 2 of Treatment Period 3.

          -  Female subjects must meet one of the following criteria: 1) If of childbearing
             potential, female subjects agree to use two contraceptive regimens or remain abstinent
             during the study; or 2) if of non-childbearing potential, female subjects should be
             surgically sterile or in a menopausal state.

        Exclusion Criteria:

          -  A significant history and/or presence of hepatic, renal, cardiovascular, pulmonary,
             neurological, psychiatric, gastrointestinal, hematological, immunologic,
             ophthalmologic, metabolic, or oncological disease, or any other medical issue that
             would, in the opinion of the Investigator, present undue risk for the subject in the
             study.

          -  A history of suicidal behavior within 24 months of Screening, has answered YES to
             questions 3, 4, or 5 on the C-SSRS at Screening or at any clinic admission, or is
             currently at risk of suicide in the opinion of an Investigator.

          -  A recent history (within 6 months prior to Screening) of substance use disorder
             (including alcohol) (as judged by the Investigator) or regularly consumes >2 alcoholic
             drinks/day during the last 3 months prior to Screening (1 alcoholic drink is
             approximately equivalent to: beer [284 mL], wine [125 mL/4 ounces], or distilled
             spirits [25 mL/1 ounce]). Subjects who consume 3 drinks per day but less than 14
             drinks per week may be enrolled at the discretion of the Investigator.

          -  Demonstrates simulator sickness questionnaire scores which are indicative of simulator
             sickness as defined in the driving simulation operations manual.

          -  Regularly consumes excessive amounts of caffeine, defined as greater than 6 servings
             of coffee, tea, cola, or other caffeinated beverages per day.

          -  Smokes more than 10 cigarettes or e-cigarettes, or 3 cigars or pipes per day, or is
             unable to refrain from smoking during study visits.

          -  Has been exposed to an investigational drug or device within the 30 days, or 5 half
             lives (if known), whichever is longer, prior to Screening.

          -  Has used a prescription or over-the-counter medication known to cause sedation within
             7 days prior to Admission for Period 1 and is unwilling or unable to refrain from
             sedating medication use during study participation.

          -  Has used any benzodiazepine, barbiturate, or GABAA modulator (e.g., eszopiclone,
             zopiclone, zaleplon, and zolpidem) within 28 days prior to Admission for Period 1 or
             is unwilling or unable to refrain from medication use during study participation.

          -  Has a history of hepatitis B surface antigen, hepatitis C antibodies, or human
             immunodeficiency virus (HIV) antibodies 1 or 2.

          -  Is pregnant or breastfeeding at Screening or any clinic admission or will attempt to
             become pregnant at any time during study participation.

          -  Has a clinically significant abnormal finding on 6-lead electrocardiogram (ECG) at
             Screening or at any clinic admission. The ECG may be repeated once for confirmatory
             purposes if initial values obtained exceed the limits specified.

          -  Has a positive urine test for drugs of abuse (other than tetrahydrocannabinol (THC))
             or Breath Alcohol Concentration (BrAC) > 0.0 at Screening or any admission.

          -  Has any clinically significant abnormal physical examination finding at Screening or
             any clinic admission.

          -  Participates in night shift work.

          -  Has traveled across ≥1 time zone in the 2 weeks prior to Admission for Period 1 or is
             expected to travel across ≥1 time zone during the study.

          -  Is investigative site personnel or their immediate families (spouse, parent, child, or
             sibling whether biological or legally adopted).