Interactions Between Cannabinoids and Cytochrome P450-Metabolized Drugs
Condition: Drug-Interactions
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will evaluate drug-drug interactions between cannabis extracts containing
      Tetrahydrocannabinol (THC) and THC+ Cannabinoids (CBD) and probe drugs for select CYP450
      pathways including: caffeine (CYP1A2), omeprazole (CYP2C19), losartan (CYP2C9),
      dextromethorphan (CYP2D6), and midazolam (CYP3A).
    

Detailed description: 
      Despite the widespread use and availability of cannabis products, substantive deficiencies
      remain regarding the potential risks for cannabis or cannabinoids to precipitate adverse
      interactions with conventional drugs. Evidence from the few systematic clinical studies that
      have been conducted suggests that THC and CBD can inhibit metabolism of other drugs, via
      interactions with cytochrome P450 (CYP) enzymes, a large family of enzymes involved in the
      metabolism of numerous drugs and foreign chemicals in the body. Accordingly, evaluating the
      potential for drug-drug interactions between cannabis-derived products and common
      CYP-metabolized drugs merits further investigation. This double-blind, randomized crossover
      design study will evaluate whether, and to what extent, oral administration of cannabis
      extracts containing high doses of CBD and/or THC alter the pharmacokinetics of 5 drugs
      metabolized via CYP pathways including: caffeine (CYP1A2), omeprazole (CYP2C19), losartan
      (CYP2C9), dextromethorphan (CYP2D6), and midazolam (CYP3A). Healthy adults will complete
      three experimental dosing sessions, in which participants will orally ingest brownies
      containing (1) a high THC cannabis extract with a target THC dose of 40mg, (2) a high CBD
      cannabis extract with a target CBD dose of 1350mg + a THC dose of 40mg, or (3) placebo. In
      all three experimental dosing sessions, consumption of the cannabis extract infused brownie
      will be followed by ingestion of a drug "cocktail" comprised of commercial formulations of
      therapeutic or subtherapeutic doses of each drug. This collection of probe drugs, coined the
      Inje Cocktail, has been demonstrated to be safe, both administered alone and with various
      CYP450 inhibitors. At baseline and following administration of the study drugs, a battery of
      subjective, physiological, and cognitive performance assessments will be completed and
      biological specimens obtained. Each session will consist of a 12-hour outpatient drug
      administration visit and a 1-hour outpatient visit the subsequent day for additional
      biospecimen collection, cognitive testing, and subjective drug effect questionnaires. The
      study will conclude when 18 participants complete all 3 experimental sessions. The outcomes
      of this study will be useful to inform clinical decision-making regarding co-administration
      of cannabinoid-containing products with drugs that are either commonly prescribed by
      physicians or readily available over-the-counter.
    

Intervention name(s): Inje cocktail; THC Cannabis extract; THC/CBD Cannabis Extract
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Acute drug exposure; Acute drug exposure; Acute drug exposure
Intervention MeSH terms: Dronabinol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Basic Science