Single-Dose Pharmacokinetics and Preliminary Safety Assessment with Use of CBD-Rich Hemp Nutraceutical in Healthy Dogs and Cats

Abstract

Simple SummaryThe use of cannabidiol (CBD)-rich hemp-based nutraceuticals is increasing in dogs and cats for disorders related to anxiety, seizures, cancer and pain. To date, there is little information related to appropriate dosing or long-term effects on serum chemistry or complete blood counts (CBC), and little data on the pharmacokinetics of single- or long-term dosing in dogs and cats. Single-dose pharmacokinetics and preliminary 12-week serum chemistry and complete blood counts are reported here showing short pharmacokinetic half-lives of cannabidiol in dogs and cats, with cats showing far lower oral absorption kinetics or rapid elimination suggesting dosing may differ between the two species. Fortunately, there were no changes in physical examination and few changes in the CBC and serum chemistry parameters suggesting the relative safety of oral supplementation over 12 weeks. One of the eight cats displayed a persistent rise in the serum alanine amino transferase (ALT) enzyme outside of the reference range and cats commonly displayed excessive licking and head shaking with administration of the oil. Based on these and other recent data, CBD-rich hemp nutraceuticals appear to be safe in healthy adult dogs, while more work in cats is needed to fully understand utility and absorption.AbstractThe use of CBD-rich hemp products is becoming popular among pet owners with no long-term safety data related to consumption in adult dogs and cats. The purpose of this study was to determine the single-dose oral pharmacokinetics of CBD, and to provide a preliminary assessment of safety and adverse effects during 12-week administration using a hemp-based product in healthy dogs and cats. Eight of each species were provided a 2 mg/kg total CBD concentration orally twice daily for 12 weeks with screening of single-dose pharmacokinetics in six of each species. Pharmacokinetics revealed a mean maximum concentration (Cmax) of 301 ng/mL and 43 ng/mL, area under the curve (AUC) of 1297 ng-h/mL and 164 ng-h/mL, and time to maximal concentration (Tmax) of 1.4 h and 2 h, for dogs and cats, respectively. Serum chemistry and CBC results showed no clinically significant alterations, however one cat showed a persistent rise in alanine aminotransferase (ALT) above the reference range for the duration of the trial. In healthy dogs and cats, an oral CBD-rich hemp supplement administered every 12 h was not detrimental based on CBC or biochemistry values. Cats do appear to absorb or eliminate CBD differently than dogs, showing lower serum concentrations and adverse effects of excessive licking and head-shaking during oil administration.

<p>Cannabinoid, Terpene, and Heavy Metal Analysis of 29 Over-the-Counter Commercial Veterinary Hemp Supplements</p>

“…[30][31][32][33] In general, the milligram quantity of total terpenes across products ranges from 0.015-6.7 mg/ mL or gram with only 6 products with over 1 mg/mL or gram of total terpenes. Further examination for any single terpene at concentrations higher than 1 mg/mL leaves only three products (#18, 19,25) that have a single terpene at that level. Overall, total terpenes for most products would be similar in concentrations to some of the minor cannabinoids observed, making it difficult to elucidate exactly whether alternate cannabinoids and/or terpenes are exhibiting some of the synergy observed as the "entourage effect" discussed in the literature.…”

“…That said, in the veterinary literature there has been some initial pilot pharmacokinetic, safety and pilot clinical trials that provide some insights for veterinarians regarding dosing regimens. [15][16][17][18][19] The objectives of this study were to provide information regarding the important plant constituents including cannabinoids, terpenes and heavy metal contamination (lead, arsenic, mercury and cadmium) in commercial products obtained through internet commerce using liquid chromatography with diode array detection and mass spectroscopy (LC-DAD/MS), headspace gas chromatography (HS-GC-FID) and inductive coupled plasma mass spectroscopy (ICP-MS), respectively. The cannabinoids analyzed included CBD, THC, Δ8-THC, CBG, CBN, CBC, THCV, CBDV and derived acids CBDA, THCA, and CBGA.…”

Pharmacokinetic and Safety Evaluation of Various Oral Doses of a Novel 1:20 THC:CBD Cannabis Herbal Extract in Dogs

“…The PK of CBD and/or THC after administration of various CHE formulations and dose regimens have recently been published in dogs ( 1 , 12 , 13 , 15 – 17 ). The range of CBD and THC doses previously reported guided the dose range selected for this trial (2–10 mg CBD and 0.1–0.5 mg THC per kg bw), with the exception of those studies using much higher THC doses ( 16 , 17 ).…”

“…Certificates of Analysis were provided by Aurora Cannabis Inc. for all product batches used in the study. Dose regimens for both the PK and multidose study phases were based on CBD dose regimens used in previously published studies ( 1 , 12 , 13 ).…”

A Review of Hemp as Food and Nutritional Supplement

“…Despite the large consumption of CBD as a nutritional supplement, evidence from pre-clinical and clinical studies exploring the effects of CBD as a dietary ingredient is scarce to nonexisting. In one pre-clinical study conducted in eight dogs and eight cats, 61 CBD administered at the daily dose of 4 mg/kg for 12 weeks did not cause any alteration in complete blood count or serum chemistry, with the exception of one cat showing persistent abnormalities in alanine aminotransferase levels. Dogs presented few adverse events, including loose stool and vomiting occurring for < 5% of the observation time, while cats showed multiple adverse events, including licking and head shaking, observed for 35.4% and 25.2% of the observation time, respectively.…”