The acute and chronic pharmacokinetics and pharmacodynamics of oral cannabidiol with and without low doses of delta-9-tetrahydrocannabinol

口服大麻二酚(含或不含低剂量Δ9-四氢大麻酚)的急性及慢性药代动力学和药效学研究

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Abstract

Hemp products [cannabis with ≤0.3% Δ9-tetrahydrocannabinol (Δ9-THC)] are federally legal, but few controlled experiments have explored drug test results, pharmacokinetics, or pharmacodynamics. Healthy adults (n = 60) self-administered 1.5 mL medium-chain triglyceride (MCT) oil containing 100 mg cannabidiol (CBD) and either 0, 0.5, 1, 2, 2.8, or 3.7 mg Δ9-THC (n = 10 per group). The study included an 8-hour acute dose laboratory session (Phase 1), a 14-day outpatient drug exposure period with twice daily dosing (Phase 2) and a 7-day washout period (Phase 3). Measures including urine, blood, subjective drug effects, and cognitive and psychomotor performance were assessed repeatedly throughout the experiment. At least one participant receiving Δ9-THC doses of 1.0 mg or greater had at least 1 positive urine drug test (Δ9-THC-COOH immunoassay screen ≥50 ng/mL and LC-MS/MS confirmation ≥15 ng/mL) during Phase 1 and the number of positive urine samples increased with Δ9-THC dose. Positive urine drug tests were observed during the Phase 2 outpatient drug exposure period from at least one participant in each dose condition that contained any amount of Δ9-THC. One urine specimen in the CBD only dose condition tested positive during Phase 2. Two positive urine samples were observed after the 1-week washout (Day 21). Blood concentrations of Δ9-THC were very low in all dose conditions, and there were no significant differences between the CBD only dose group and Δ9-THC-containing dose groups on any pharmacodynamic outcome. Individuals subject to drug testing should recognize that hemp products contain detectable amounts of Δ9-THC. Conventional drug testing cannot reliably distinguish between illicit cannabis and legal hemp-derived product use, and a positive urine Δ9-THC test may result from low doses that do not produce intoxication or impairment.

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