Using Imaging to Assess Effects of THC on Brain Activity
Condition: Intoxication Alcohol; Intoxication THC; Intoxication Combined Alcohol THC
MeSH terms: Alcoholic Intoxication
Study type: Interventional

Summary: 
      This study will assess effects of tetrahydrocannabinol (THC) and THC + alcohol in marijuana
      users on prefrontal brain activity, using functional near-infrared spectroscopy (fNIRS)
      during resting state and during memory task performance. Participants will complete fNIRS
      testing 120 minutes following THC or identical placebo (Phase 2A), or THC/ethanol,
      THC/placebo ethanol, placebo THC/ethanol, and placebo THC/placebo ethanol (Phase 2B), and
      oxygenated hemoglobin (HbO) concentration will be measured.
    

Detailed description: 
      This study will assess the effects of THC intoxication using dronabinol (synthetic THC) on
      the oxyhemoglobin (HbO) signal during resting state and task-based activation in the
      prefrontal cortex (PFC) and resting state connectivity, as well as on neurocognitive task
      performance and correlations between these measurements and clinical signs of intoxication.
      Participants will be 150 adults who use marijuana at least monthly (aged 18-55) will be
      recruited to participate in this study. Participants will be given up to 80 mg of dronabinol,
      an FDA-approved synthetic form of THC that is used to treat loss of appetite that causes
      weight loss in people with AIDS. THC is the principle psychoactive drug in marijuana. The
      study will be conducted in regular cannabis users who present at their first study visit with
      a positive urine screen for THC metabolites.

      Phase 2A. Investigate the effect of THC on fNIRS brain signature and its association with
      self-reported intoxication, laboratory measures of impairment, and the gold-standard
      behavioral field test of driving impairment used by law enforcement, the primary classifier.

      Phase 2B. Examine potential interaction following co-administration of THC with oral ethanol
      exposure in healthy volunteers. Phase II is a randomized, double-blind, placebo-controlled, 2
      by 2 crossover study of effect of dronabinol, ethanol, and combined dronabinol and ethanol on
      brain activation and connectivity as measured by fNIRS.
    

Intervention name(s): Dronabinol; Ethanol; Placebo dronabinol; Placebo ethanol
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): Dronabinol at physician determined doses of 10-80mg designed to produce intoxication.; Oral Ethanol, dosed to obtain a breath alcohol concentration (BrAC) of approximately 0.05 BrAC (equal to 1-2 standard drinks).; Identical in appearance to active dronabinol (overencapsulation of both active and placebo dronabinol); Placebo ethanol will consist of diet soda used in the active ethanol condition with 0.25ml ethanol floated on top to provide the odor of ethanol and blind the study drug.
Other intervention name(s): oral THC; oral ethanol; placebo oral THC; oral placebo ethanol
Intervention MeSH terms: Ethanol; Dronabinol
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: In Phase 2A, a double-blind placebo-controlled, random order cross-over study of single dose dronabinol, participants received dronabinol or identical placebo on two separate study visits in randomized order.
In Phase 2B, a randomized, double-blind, 4-treatment, 4-period, crossover study with THC or placebo administration and ethanol or placebo administration, participants were randomly assigned to 1 of 24 sequences of each of the following treatments: placebo dronabinol and placebo ethanol, placebo dronabinol and ethanol, dronabinol and placebo ethanol, and dronabinol and ethanol.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: fNIRS; THC; Intoxication