Eye Tracking as a Biomarker of Cannabis Effects
Condition: Cannabis Use; Pain, Acute
MeSH terms: Acute Pain; Marijuana Abuse
Intervention: Cannabis
Intervention description: Smoked active cannabis (7% THC) vs. placebo inactive cannabis (0% THC)
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Each volunteer will participate in two sessions in a cross-over fashion (active cannabis vs. inactive placebo cannabis)
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 1.0
Sex: All
Minimum age: 21 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      Biomarkers of recent drug use and intoxication have societal relevance, in that they are used
      by law enforcement and other agencies to detect drug impairment. For instance, a breathalyzer
      can quickly and accurately detect blood alcohol content (BAC) to indicate if a person is
      under the influence of alcohol; however, there is currently no similar way to quickly detect
      if a person is under the influence of cannabis. In light of increasing cannabis use, it is
      important to define a quantitative, objective method of determining recent use and
      intoxication.

      The link between changes in eye characteristics (e.g. movement, pupil dilation) and cannabis
      use is documented (Peragallo et al. 2013), but insufficiently characterized. Certain outcomes
      of eye behavior are known to be affected by recent cannabis use (e.g. the eyes' ability to
      converge on a target; Stapleton et al 1986), while findings are mixed regarding other
      outcomes (e.g. the eyes' ability to smoothly follow a target; Fant et al. 1998). Thus, the
      goal of this study is to identify a characteristic pattern of eye behavior, defined by
      performance on a battery of four eye tasks, as a function of recent cannabis use (7% vs. 0%
      THC).

      Using 30 healthy cannabis users (15 men, 15 women), this study will be one of the first to
      assess changes in eye behavior as a function of recent cannabis use within a quantified
      virtual reality (VR) environment. This study will examine the effect of smoked cannabis (7%
      vs. 0% THC) on individual eye movements, with the goal of defining the utility of the eyes as
      potential objective indicators of cannabis use and intoxication. Four eye tests (nystagmus,
      smooth pursuit, convergence, and pupillary light response; outlined below), which previous
      literature has defined as effective in detecting recent drug use (including opioids and
      alcohol; Murillo et al. 2004), have been compiled into a 5-minute task battery using a VR
      headset environment equipped with high frequency infrared eye trackers (the HTC Vive with
      Pupil Labs Tracking). This 5-minute VR battery of four eye tests will be administered prior
      to cannabis consumption as a baseline, and then at 0, 15, 30, 45, 60, 75, 90, 105, 120, and
      165 min after cannabis, with the goal of comparing baseline values to the ten post-cannabis
      timepoints to detect changes in eye behavior as a function of cannabis intoxication. The
      study will also utilize a battery of subjective-effects and mood visual analogue scales
      (0-100 mm; e.g. 'Good Drug Effect') prior to the eye test battery at each timepoint, allowing
      us to correlate each outcome of the eye tasks to subjectively reported cannabis impairment
      and mood.

      In addition to measuring eye behavior as a function of cannabis use, the training session of
      this study will be used to also collect exploratory data on the relationship between pupil
      dilation and experimental pain. Using Quantitative Sensory Testing (Medoc TSA-II NeuroSensory
      Analyzer), thermal pain threshold and tolerance will be induced using a cold stimulus (4.0°C;
      induced with a 30 x 30 mm Peltier thermode, which is 1.5" square metal applicator that is
      connected to the TSA-II NeuroSensory Analyzer device and software, and produces an ongoing
      cold sensation applied to the lower palm of the participant's non-dominant hand).
      Participants will indicate first feelings of pain (pain threshold), and when the pain becomes
      too much to bear (pain tolerance) by pressing a button on a controller connected to the
      TSA-II. Throughout exposure to the cold stimulus, changes in pupil size to the patient's
      subjectively reported pain latencies will be recorded.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males/non-pregnant females

          -  Report smoking cannabis ≥1 day per week

          -  Able to perform all study procedures

        Exclusion Criteria:

          -  Meeting DSM-V criteria for severe substance use

          -  Use of illicit drugs ≥1 day/week in the prior 4 weeks

          -  Abnormality with the eyes which may affect the eye tracking technology such as color
             blindness, naturally occurring nystagmus, amblyopia, strabismus, age-related macular
             degeneration (AMD), cataract, diabetic eye disease, glaucoma, dry eye, extreme
             refractive error, bacterial or viral infections of the eye

          -  7. User of supplemental oxygen