Limited pharmacokinetic and safety study with daily feeding of hemp pellets in domestic goats: cannabidiolic acid is absorbed and retained better than cannabidiol.

Objective: To determine serum pharmacokinetics and evaluate safety after oral cannabidiol (CBD)/cannabidiolic acid (CBDA)-rich hemp pellets administrated to goats.

Methods: Eight 7-year-old female goats received 3 mg/kg CBD and 2 mg/kg CBDA from hemp pellets daily for 14 days. Serum samples were collected at 0, 0.5, 1, 2, 4, 8, 12, and 24 hours and at 7 and 14 days, from September through November of 2023. Serum concentrations for 12 cannabinoid/metabolites were determined using LC-MS. Pharmacokinetic parameters were calculated using noncompartmental analysis. Chemistry panels and CBCs were performed before administration and after 14 doses.

Results: Only CBDA was measurable within the first 24 hours. The maximum geometric mean serum concentration was 30.0 ng/mL (range, 21.3 to 59.2 mg/mL), the median time of maximum serum concentration was 18 hours (range, 4 to 24 hours), and the geometric mean area under the plasma concentration-versus-time curve was 410.2 ng·h/mL (range, 174.4 to 919.3 ng·h/mL). Mean ± SD serum concentrations 6 hours after administration on days 7 and 14 were 2.2 ng/mL ± 1.8 and 1.7 ng/mL, respectively, for CBD, and they were 52.4 ± 19.7 ng/mL and 53.0 ± 16.6 ng/mL, respectively, for CBDA.

Conclusions: The absorption of CBDA was markedly higher than other cannabinoids, with no differences between days 7 and 14, suggesting stable serum concentrations within 7 days.

Clinical relevance: Goats absorb CBDA from the rumen, and 3 mg/kg CBDA every 24 hours reaches similar serum concentrations to monogastric species. Due to low serum CBD concentrations and rapid metabolism, CBDA might be a preferable alternative to CBD in ruminant species.