TY - JOUR T1 - Pharmacokinetics of Cannabidiol, Cannabidiolic Acid, Δ9-Tetrahydrocannabinol, Tetrahydrocannabinolic Acid and Related Metabolites in Canine Serum After Dosing With Three Oral Forms of Hemp Extract. AU - Wakshlag,Joseph J, AU - Schwark,Wayne S, AU - Deabold,Kelly A, AU - Talsma,Bryce N, AU - Cital,Stephen, AU - Lyubimov,Alex, AU - Iqbal,Asif, AU - Zakharov,Alexander, Y1 - 2020/09/04/ PY - 2020/05/07/received PY - 2020/07/03/accepted PY - 2020/10/26/entrez PY - 2020/10/27/pubmed PY - 2020/10/27/medline KW - cannabidiol KW - cannabidiolic acid KW - dog KW - hemp KW - pharmacokinetics KW - tetrahydrocannabinol KW - tetrahydrocannabinolic acid SP - 505 EP - 505 JF - Frontiers in veterinary science JO - Front Vet Sci VL - 7 N2 - Cannabidiol (CBD)-rich hemp extract use is increasing in veterinary medicine with little examination of serum cannabinoids. Many products contain small amounts of Δ9-tetrahydrocannabinol (THC), and precursor carboxylic acid forms of CBD and THC known as cannabidiolic acid (CBDA) and tetrahydrocannabinolic acid (THCA). Examination of the pharmacokinetics of CBD, CBDA, THC, and THCA on three oral forms of CBD-rich hemp extract that contained near equal amounts of CBD and CBDA, and minor amounts (<0.3% by weight) of THC and THCA in dogs was performed. In addition, we assess the metabolized psychoactive component of THC, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and CBD metabolites 7-hydroxycannabidiol (7-OH-CBD) and 7-nor-7-carboxycannabidiol (7-COOH-CBD) to better understand the pharmacokinetic differences between three formulations regarding THC and CBD, and their metabolism. Six purpose-bred female beagles were utilized for study purposes, each having an initial 7-point, 24-h pharmacokinetic study performed using a dose of 2 mg/kg body weight of CBD/CBDA (~1 mg/kg CBD and ~1 mg/kg CBDA). Dogs were then dosed every 12 h for 2 weeks and had further serum analyses at weeks 1 and 2, 6 h after the morning dose to assess serum cannabinoids. Serum was analyzed for each cannabinoid or cannabinoid metabolite using liquid chromatography and tandem mass spectroscopy (LC-MS/MS). Regardless of the form provided (1, 2, or 3) the 24-h pharmacokinetics for CBD, CBDA, and THCA were similar, with only Form 2 generating enough data above the lower limit of quantitation to assess pharmacokinetics of THC. CBDA and THCA concentrations were 2- to 3-fold higher than CBD and THC concentrations, respectively. The 1- and 2-week steady-state concentrations were not significantly different between the two oils or the soft chew forms. CBDA concentrations were statistically higher with Form 2 than the other forms, showing superior absorption/retention of CBDA. Furthermore, Form 1 showed less THCA retention than either the soft chew Form 3 or Form 2 at weeks 1 and 2. THC was below the quantitation limit of the assay for nearly all samples. Overall, these findings suggest CBDA and THCA are absorbed or eliminated differently than CBD or THC, respectively, and that a partial lecithin base provides superior absorption and/or retention of CBDA and THCA. SN - 2297-1769 UR - https://www.unboundmedicine.com/medline/citation/33102539/Pharmacokinetics_of_Cannabidiol_Cannabidiolic_Acid_Δ9_Tetrahydrocannabinol_Tetrahydrocannabinolic_Acid_and_Related_Metabolites_in_Canine_Serum_After_Dosing_With_Three_Oral_Forms_of_Hemp_Extract_ DB - PRIME DP - Unbound Medicine ER -