Feeding Decreases the Oral Bioavailability of Cannabidiol and Cannabidiolic Acid in Hemp Oil in New Zealand White Rabbits (oryctolagus Cuniculus)

OBJECTIVE To determine the pharmacokinetics of a solution containing cannabidiol (CBD) and cannabidiolic acid (CBDA), administered orally in 2 single -dose studies (with and without food), in the domestic rabbit ( Oryctolagus cuniculus ). ANIMALS 6 healthy New Zealand White rabbits. PROCEDURES In phase 1, 6 rabbits were administered 15 mg/kg CBD with 16.4 mg/kg CBDA orally in hemp oil. In phase 2, 6 rab - bits were administered the same dose orally in hemp oil followed by a food slurry. Blood samples were collected for 24 hours to determine the pharmacokinetics of CBD and CBDA. Quantification of plasma CBD and CBDA concentra - tions was determined using a validated liquid chromatography-mass spectrometry (LC -MS) assay. Pharmacokinet - ics were determined using noncompartmental analysis. RESULTS For CBD, the area under the curve extrapolated to infinity (AUC) 0- infinity was 179.8 and 102 hours X ng/mL, the maximum plasma concentration (C max ) was 30.4 and 15 ng/mL, the time to C max (t max ) was 3.78 and 3.25 hours, and the ter - minal half-life (t 1/2 lambda ) was 7.12 and 3.8 hours in phase 1 and phase 2, respectively. For CBDA, the AUC 0- infinity was 12,286 and 6,176 hours X ng/mL, C max was 2,573 and 1,196 ng/mL, t max was 1.07 and 1.12 hours, and t 1/2 lambda was 3.26 and 3.49 hours in phase 1 and phase 2, respectively. Adverse effects were not observed in any rabbit. CLINICAL RELEVANCE CBD and CBDA reached a greater C max and had a longer t 1/2 lambda in phase 1 (without food) compared with phase 2 (with food). CBDA reached a greater C max but had a shorter t 1/2 lambda than CBD both in phase 1 and phase 2. These data may be useful in determining appropriate dosing of cannabinoids in the domestic rabbit.