TY - JOUR
T1 - Pharmacokinetics and pharmacodynamics of five distinct commercially available hemp-derived topical cannabidiol products
AU - Zamarripa, C. Austin
AU - Tilton, Hayleigh E.
AU - Lin, Spencer
AU - Cone, Edward Jackson
AU - Winecker, Ruth E.
AU - Flegel, Ronald R.
AU - Kuntz, David
AU - Beals, Melissa
AU - Jacques, Martin
AU - Clark, Michael
AU - Welsh, Eric R.
AU - Wagner, Lynn
AU - Bonn-Miller, Marcel O.
AU - Vandrey, Ryan
AU - Spindle, Tory R.
N1 - Publisher Copyright:
© The Author(s) 2024. Published by Oxford University Press. All rights reserved.
PY - 2024/3/1
Y1 - 2024/3/1
N2 - Products containing cannabidiol (CBD) have proliferated after the 2018 Farm Bill legalized hemp (cannabis with ≤0.3% delta-9tetrahydrocannabinol (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: (i) an acute drug application laboratory session, (ii) a 9-day outpatient phase with twice daily product application (visits occurred on Days 2, 3, 7 and 10) (iii) 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 and 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 US federal workplace drug testing criteria (immunoassay cut-off of 50 ng/mL and confirmatory LC–MS-MS cut-off of 15 ng/mL). Unexpectedly, nine participants (seven lotions, one patch and one gel) exhibited Δ9-THC oral fluid concentrations ≥2 ng/mL (current US 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.
AB - Products containing cannabidiol (CBD) have proliferated after the 2018 Farm Bill legalized hemp (cannabis with ≤0.3% delta-9tetrahydrocannabinol (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: (i) an acute drug application laboratory session, (ii) a 9-day outpatient phase with twice daily product application (visits occurred on Days 2, 3, 7 and 10) (iii) 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 and 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 US federal workplace drug testing criteria (immunoassay cut-off of 50 ng/mL and confirmatory LC–MS-MS cut-off of 15 ng/mL). Unexpectedly, nine participants (seven lotions, one patch and one gel) exhibited Δ9-THC oral fluid concentrations ≥2 ng/mL (current US 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.
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U2 - 10.1093/jat/bkae001
DO - 10.1093/jat/bkae001
M3 - Article
C2 - 38217086
AN - SCOPUS:85186550781
SN - 0146-4760
VL - 48
SP - 81
EP - 98
JO - Journal of analytical toxicology
JF - Journal of analytical toxicology
IS - 2
ER -