Results of an Exploratory Crossover Pharmacokinetic Study Evaluating a Natural Hemp Extract-Based Cosmetic Product: Comparison of Topical and Oral Routes of Administration.

内容摘要

Background: Hemp extracts are used topically as cosmetic products and may be ingested as dietary supplements. Some users report positive carboxy delta-9-tetrahydrocannabinol (COOH-THC) urinary tests following their use. This study evaluated systemic exposure to natural hemp extract-based cosmetic (NHEC) bioactive molecules following a single dose of oral or topical application and assessed urine THC positivity. Methods: Twenty healthy adults (18-50 years, males and females) of a randomized, open-label, single-dose, crossover study received the NHEC orally or topically with a 15-day washout period. Plasma samples were analyzed for cannabidiol (CBD), tetrahydrocannabinol (THC), and their metabolites using a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were calculated by non-compartmental analysis (Phoenix® WinNonlin® 8.4, Pharsight Inc., Chatham, NJ, USA). Urine samples were tested for COOH-THC using commercial test strips. Results: All analytes, except CBD and 7-hydroxy cannabidiol (7-OH-CBD), were below the limit of quantification. Oral NHEC administration resulted in a faster Tmax (3 h vs. 24 h) and a higher AUC0-24 (281 vs. 19 h·ng/mL) for CBD compared to topical administration. Urine was positive for COOH-THC in 38% of participants receiving an oral dose. Conclusions: A single oral dose resulted in detectable plasma CBD and 7-OH-CBD, whereas topical administration produced low and frequently BLQ CBD concentrations with 7-OH-CBD and THC-related analytes not quantifiable. Urine COOH-THC tests were positive only in participants after oral use of an NHEC but not with topical use. Given the absence of THC in the product and the lack of CBD-to-THC conversion in humans, the cause of urine positivity remains unclear.