Single-Dose Pharmacokinetics and Preliminary Safety Assessment with Use of CBD-Rich Hemp Nutraceutical in Healthy Dogs and Cats - 2019
Kelly A. Deabold, Wayne S. Schwark, Lisa Wolf, and Joseph J. Wakshlag
The purpose of this study was to determine the pharmacokinetics and preliminary safety of an oral canine whole-plant CBD-infused soft chew and oral feline CBD-infused fish oil. It was hypothesized that there would be no significant changes in complete blood count (CBC) or serum biochemistry values and that the only adverse effects observed would be associated with oral administration of the product, particularly in cats.
Eight fasted, healthy, purpose-bred research Beagle dogs with a mean age of 3.2 years ranging from 11 months to 5 years of age, weighing an average of 9.7 kg (7.4 to 12.0 kg), were included in the study. The dogs were offered ElleVet Mobility Chews (ElleVet Sciences; Portland, ME, USA) at a dose of 2 mg/kg twice daily for 84 days. Small chews contained 10 mg of CBD as a 50% mix of CBD (5 mg per chew) and CBDA (CBDA—5 mg per chew). Large soft chews containing approximately 15 mg of CBD (equal mix of CBD/CBDA) were also used in the study.
Prior to the start of and every 4 weeks over the course of the study, 5 mm of blood was collected via jugular venipuncture in sterile syringes. Samples were split into two tubes, a red top coagulation tube and an ethylenediaminetetraacetic acid tube. Red top tubes were spun in a refrigerated centrifuge for 15 min at 1512× g after being allowed to clot for 10 min. Blood samples were packaged and sent priority-overnight for analysis to ANTECH Diagnostics (Fountain Valley, CA, USA). A white blood cell count, red blood cell count, hemoglobin, hematocrit (HCT), Mean corpuscle volume, mean corpuscle hemoglobin concentration, mean corpuscle hemoglobin, and platelet count along with a complete differential was performed. A serum chemistry screen was performed consisting of, albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, calcium, chloride, cholesterol, creatinine, creatine kinase, gamma glutamyl transferase, glucose, globulin, magnesium, phosphorus, potassium, sodium, total bilirubin, total protein, triglycerides, and urea nitrogen.
Eight fasted, healthy, purpose-bred domestic shorthair research cats with a mean age of 4.5 years ranging from 2–6.3 years of age, weighing an average of 4.2 kg (3.3 to 5.2 kg) were included in the study. The cats were dosed with CBD-infused fish oil (50/50% mix of CBD and CBDA; ElleVet Sciences; Portland, ME, USA) at 2 mg/kg. The total dose per 24 h period was 4 mg/kg, for 84 days. The initial pharmacokinetic dosing was done with capsules to ensure consumption and all cats were fasted from the previous day and were not fed until 6 h after initial dosing.
Prior to the start of and every 4 weeks throughout the course of the study, 5 mL of blood was collected via jugular venipuncture in sterile syringes. Samples were split into two tubes, processed as described above, and sent priority-overnight for CBC and serum chemistries to ANTECH Diagnostics (Fountain Valley, CA, USA). The same parameters as described previously were measured.
On the first day of dosing, 3 mL of blood was collected for a pharmacokinetic (PK) analysis from only 6 of the 8 dogs and cats in the study at each time point.
Dogs were observed for signs of adverse events twice a day for the 12-week study. Out of 1344 total observation periods, 53 adverse events were reported. Loose stool was the most common adverse event noted among the eight dogs and occurred 44 times (3.3% of the time).
Cats were observed for signs of adverse events twice a day for the 12-week study for a total of 1344 observation periods. The main adverse effects noted included licking and head shaking, which were observed 476 (35.4%) and 339 (25.2%) times, respectively. Other adverse events noted were pacing (n = 150, 11.1%), and chomping/chewing (n = 88, 6.5%).
In this uncontrolled preliminary study dosing of 2 mg/kg twice daily mixture of CBD and CBDA showed no abnormalities in weekly physical examinations, nor any evidence of organ dysfunction as assessed by blood parameters. The canine CBD-infused chews showed no ALP elevations, with no ALP values falling outside the reference range (5–131 U/L) for any dog in the study.
The absorption of CBD in the fish oil base is less than in dogs using plant oil bases, hence larger doses may be necessary for pharmacological effects. This information is important for feline practitioners that are considering the use of CBD products in cats for anxiety, arthritis, house soiling, seizure activity, or neoplasia.
The absorption of CBD in the fish oil base is less than in dogs using plant oil bases, hence larger doses may be necessary for pharmacological effects. This information is important for feline practitioners that are considering the use of CBD products in cats for anxiety, arthritis, seizure activity, or neoplasia.
In conclusion, hemp-based CBD appears to be relatively safe in healthy populations of dogs and cats, and dogs appear to absorb CBD better than cats. The lack of serum chemistry alterations in both species is comforting as it relates to preliminary toxicity findings; however, use of CBD-rich hemp products requires monitoring of liver enzyme values.
Citations: https: //www.ncbi.nlm.nih.gov/pmc/articles/ PMC6826847
Animals (Basel). 2019 Oct; 9(10): 832.