TY - JOUR
T1 - Twice-daily oral administration of a cannabidiol and cannabidiolic acid–rich hemp extract was well tolerated in orange-winged Amazon parrots (Amazona amazonica) and has a favorable pharmacokinetic profile
AU - Sosa-Higareda, Mariana
AU - Guzman, David Sanchez Migallon
AU - Knych, Heather
AU - Lyubimov, Alex
AU - Zakharov, Alexander
AU - Gomez, Beatriz
AU - Beaufrère, Hugues
N1 - The authors thank the Center for Companion Animal Health, School of Veterinary Medicine, University of California-Davis for supporting this project with a research grant. Additionally, we thank the Richard M. Schubot Parrot Wellness and Welfare Program at the Center for Companion Animal Health, School of Veterinary Medicine, University of California-Davis for additional funding support. We also thank Ellevet Sciences (Portland, ME) for providing the hemp extract and funding for plasma concentration analysis. Special thanks to Lexi Durant, Quinn Neil, and Marissa Monopoli for the assistance in parrot handling, care, and sample processing.
PY - 2023/4
Y1 - 2023/4
N2 - OBJECTIVE To determine the pharmacokinetics of 8 cannabinoids and 5 metabolites after oral administration of single and multiple doses of a cannabidiol (CBD)-cannabidiolic acid (CBDA)–rich hemp extract to orange-winged Amazon parrots (Amazona amazonica) as well as to evaluate the extract’s adverse effects. ANIMALS 12 birds. PROCEDURES Based on pilot studies, a single-dose study based on 30/32.5 mg/kg of cannabidiol/cannabidiolic acid of a hemp extract was administered orally to 8 fasted parrots, and 10 blood samples were collected over 24 hours after administration. After a 4-week washout period, the hemp extract was administered orally to 7 birds at the previous dose every 12 hours for 7 days, and blood samples were collected at the previous time points. Cannabidiol, Δ9-tetrahydrocannabinol, cannabinol, cannabichromene, cannabigerol, cannabidiolic acid, cannabigerolic acid, Δ9-tetrahydrocannabinolic acid, and 5 specific metabolites were measured by liquid chromatography-tandem/ mass-spectrometry, and pharmacokinetic parameters were calculated. Adverse effects and changes in the plasma biochemistry and lipid panels were evaluated. RESULTS Pharmacokineticparameters for cannabidiol, cannabidiolicacid,Δ9-tetrahydrocannabinol,Δ9-tetrahydrocannabinolic acid, and the metabolite 11-hydroxy-9-tetrahydrocannabinol were established. For the multiple-dose study, cannabidiol/cannabidiolic acid mean Cmax was 337.4/602.1 ng/mL with a tmax of 30 minutes and a terminal half-life of 8.6/6.29 hours, respectively. No adverse effects were detected during the multidose study. The predominant metabolite was 11-hydroxy-9-tetrahydrocannabinol. CLINICAL RELEVANCE Twice daily oral administration of the hemp extract based on 30 mg/kg/32.5 mg/kg of cannabidiol/cannabidiolic acid was well tolerated and maintained plasma concentrations considered to be therapeutic in dogs with osteoar-thritis. Findings suggest different cannabinoid metabolism from mammals.
AB - OBJECTIVE To determine the pharmacokinetics of 8 cannabinoids and 5 metabolites after oral administration of single and multiple doses of a cannabidiol (CBD)-cannabidiolic acid (CBDA)–rich hemp extract to orange-winged Amazon parrots (Amazona amazonica) as well as to evaluate the extract’s adverse effects. ANIMALS 12 birds. PROCEDURES Based on pilot studies, a single-dose study based on 30/32.5 mg/kg of cannabidiol/cannabidiolic acid of a hemp extract was administered orally to 8 fasted parrots, and 10 blood samples were collected over 24 hours after administration. After a 4-week washout period, the hemp extract was administered orally to 7 birds at the previous dose every 12 hours for 7 days, and blood samples were collected at the previous time points. Cannabidiol, Δ9-tetrahydrocannabinol, cannabinol, cannabichromene, cannabigerol, cannabidiolic acid, cannabigerolic acid, Δ9-tetrahydrocannabinolic acid, and 5 specific metabolites were measured by liquid chromatography-tandem/ mass-spectrometry, and pharmacokinetic parameters were calculated. Adverse effects and changes in the plasma biochemistry and lipid panels were evaluated. RESULTS Pharmacokineticparameters for cannabidiol, cannabidiolicacid,Δ9-tetrahydrocannabinol,Δ9-tetrahydrocannabinolic acid, and the metabolite 11-hydroxy-9-tetrahydrocannabinol were established. For the multiple-dose study, cannabidiol/cannabidiolic acid mean Cmax was 337.4/602.1 ng/mL with a tmax of 30 minutes and a terminal half-life of 8.6/6.29 hours, respectively. No adverse effects were detected during the multidose study. The predominant metabolite was 11-hydroxy-9-tetrahydrocannabinol. CLINICAL RELEVANCE Twice daily oral administration of the hemp extract based on 30 mg/kg/32.5 mg/kg of cannabidiol/cannabidiolic acid was well tolerated and maintained plasma concentrations considered to be therapeutic in dogs with osteoar-thritis. Findings suggest different cannabinoid metabolism from mammals.
UR - https://www.scopus.com/pages/publications/85151574959
UR - https://www.scopus.com/inward/citedby.url?scp=85151574959&partnerID=8YFLogxK
U2 - 10.2460/ajvr.22.11.0197
DO - 10.2460/ajvr.22.11.0197
M3 - Article
C2 - 36795552
AN - SCOPUS:85151574959
SN - 0002-9645
VL - 84
JO - American journal of veterinary research
JF - American journal of veterinary research
IS - 4
ER -