The Acute and Chronic Pharmacokinetics and Pharmacodynamics of Oral Cannabidiol (CBD) With and Without Low Doses of Delta-9-Tetrahydrocannabinol (Δ9-THC)
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, 5510 Nathan Shock Dr, Baltimore, MD, 21224, USA.
- 2RTI International, 3040 East Cornwallis Rd., Research Triangle Park, NC, 27709, USA.
- 3Division of Workplace Programs (DWP), Substance Abuse and Mental Health Services Administration (SAMHSA), 5600 Fishers Lane, Rockville, MD, 20857, USA.
- 4Clinical Reference Laboratory, 8433 Quivira Rd, Lenexa, KS, 66214, USA.
- 5Charlotte’s Web, 700 Tech Court, Louisville, CO, 80027, USA.
Affiliationer
Introduction: 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.
Methods: Healthy adults (n = 60) self-administered 1.5 mL medium-chain triglyceride (MCT) oil containing 100 mg cannabidiol (CBD) and either 0 mg, 0.5 mg, 1 mg, 2 mg, 2.8 mg 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.
Results: 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 ≥50ng/mL and LC-MS/MS confirmation ≥15ng/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.
Conclusions: 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.
