The acute and chronic pharmacokinetics and pharmacodynamics of oral cannabidiol with and without low doses of delta-9-tetrahydrocannabinol
David Wolinsky 1 , C Austin Zamarripa 1 , Tory R Spindle 1 , McKenna Klausner 1 , Edward J Cone 1 , Ruth E Winecker 2 , Svante Vikingsson 2 , Ronald R Flegel 3 , Eugene D Hayes 3 , Lisa S Davis 3 , David Kuntz 4 , Marcel Bonn-Miller 5 , George E Bigelow 1 , Ryan Vandrey 1
- 1Behavioral Pharmacology Research Unit, Johns Hopkins University School of Medicine, Baltimore, MD 21224, United States.
- 2RTI International, Research Triangle Park, NC 27709, United States.
- 3Division of Workplace Programs (DWP), Substance Abuse and Mental Health Services Administration (SAMHSA), Rockville, MD 20857, United States.
- 4Clinical Reference Laboratory, Lenexa, KS 66214, United States.
- 5Charlotte’s Web, Louisville, CO 80027, United States.
Affiliationer
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.
© The Author(s) 2025. Published by Oxford University Press.
