The acute and chronic pharmacokinetic oral fluid profile of oral cannabidiol (CBD) with and without low doses of delta-9-tetrahydrocannabinol (Δ9-THC) in healthy human volunteers

Abstract

Δ9-tetrahydrocannabinol (Δ9-THC)-dominant cannabis use can cause impairment and risks to workplace safety, which makes the detection of Δ9-THC in oral fluid (OF) important for workplace drug testing. However, cannabidiol (CBD)-dominant cannabis sold as legal hemp products (≤0.3% Δ9-THC) often contain some Δ9-THC. In the present study, participants self-administered 1.5 mL medium-chain triglyceride (MCT) oil containing 100 mg CBD and either 0, 0.5, 1.0, 2.0, 2.8 or 3.7 mg Δ9-THC twice daily for 14 days (n = 10/Δ9-THC dose condition), followed by a 7-day washout period. OF CBD, 7-hydroxy-cannabidiol (7-OH-CBD), 7-carboxy-cannabidiol (7-COOH-CBD), Δ9-THC, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-Δ9-THC), and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (Δ9-THC-COOH) were measured by LC-MS/MS (cutoff 0.025 ng/mL). Median CBD peaked at 2,198 ng/mL 0.5 h after dosing, which likely reflects a high amount of direct oral cavity deposition, followed by a rapid decline. CBD pharmacokinetics were unaffected by the co-administration of Δ9-THC. CBD and Δ9-THC metabolite concentrations were low (<2 ng/mL), with some accumulation observed for 7-COOH-CBD with twice-daily exposure. After dosing with 100 mg CBD + 0.5 mg Δ9-THC, 1/10 participants had a positive OF test (≥2 ng/mL Δ9-THC) 1.5-6 h after a single acute dose. The rate of positive test results increased as Δ9-THC doses increased to 8/10 participants testing positive after acute doses of 100 mg CBD + 2.8 or 3.7 mg Δ9-THC. A consumer of hemp products might be unaware of the risk of a positive drug test as many products do not specify that they contain Δ9-THC. One positive sample was obtained at baseline, possibly due to direct oral cavity deposition of environmental contamination. Five samples in the CBD alone group, collected 0.5 h after dosing, were positive, likely due to minimal (0.02-0.15%) conversion of CBD to Δ9-THC during analysis. Laboratories are advised to take action to identify specimens where OF Δ9-THC results could be influenced by these factors.