Pharmacokinetics and Pharmacodynamics of Five Distinct Commercially Available Hemp-derived Topical Cannabidiol (CBD) Products.

Products containing cannabidiol (CBD) have proliferated after the 2018 Farm Bill legalized hemp (cannabis with ≤0.3% delta-9-tetrahydrocannabinol, Δ9-THC). CBD-containing topical products have surged in popularity but controlled clinical studies on them are limited. This study characterized the effects of five commercially available hemp-derived high CBD/low Δ9-THC topical products. Healthy adults (N=46) received one of six study drugs: a CBD-containing cream (N =8), lotion (N =8), patch (N =7), balm (N=8), gel (N =6), or placebo (N=9; matched to an active formulation). The protocol included three phases conducted over 17 days: 1) an acute drug application laboratory session; 2) a 9-day outpatient phase with twice daily product application (visits occurred on Days 2, 3, 7, and 10); and 3) a 1-week washout phase. In each phase, whole blood, oral fluid, and urine specimens were collected and analyzed via liquid chromatography with tandem mass spectrometry (LC-MS/MS) for CBD, Δ9-THC, and primary metabolites of each and pharmacodynamic outcomes (subjective, cognitive/psychomotor, physiological effects) were assessed. Transdermal absorption of CBD was observed for three active products. On average, CBD/metabolite concentrations peaked after 7-10 days of product use and were highest for the lotion, which contained the most CBD and a permeation enhancer (vitamin E). Δ9-THC/metabolites were below the limit of detection in blood for all products and no urine samples tested "positive" for cannabis using current U.S. federal workplace drug testing criteria (immunoassay cutoff of 50ng/mL and confirmatory LC-MS/MS cutoff of 15ng/mL). Unexpectedly, nine participants (seven lotion, one patch, one gel) exhibited Δ9-THC oral fluid concentrations ≥ 2ng/mL (current U.S. federal workplace threshold for a "positive" test). Products did not produce discernable pharmacodynamic effects and were well-tolerated. This study provides important initial data on the acute/chronic effects of hemp-derived topical CBD products, but more research is needed given the diversity of products in this market.