Safety and tolerability of escalating cannabinoid doses in healthy cats

Dated: March 26, 2021

1. The purpose of this study was to determine the safety and tolerability of escalating doses of orally delivered cannabis oils predominant in cannabidiol (CBD), tetrahydrocannabinol (THC), or both CBD and THC in healthy cats.

2. In this placebo-controlled, blinded study, 20 healthy adult cats were randomized to one of five treatment groups (n = 4 per group): two placebo groups (sunflower oil [SF] or medium-chain triglyceride oil [MCT]), or three plant-derived cannabinoid oil groups (CBD in MCT, THC in MCT or CBD/THC [1.5:1] in SF). Up to 11 escalating doses of each formulation were delivered orally via syringe to fasted subjects, with at least 3 days separating doses. Safety and tolerability were determined from clinical observations, complete blood counts (CBCs) and clinical chemistry. Plasma cannabinoids (CBD, THC) and metabolites (7-COOH-CBD, 11-OH-THC) were assessed.

3. Titration to maximum doses of 30.5 mg/kg CBD (CBD oil), 41.5 mg/kg THC (THC oil) or 13.0:8.4 mg/kg CBD:THC (CBD/THC oil) was safely achieved in all subjects. All observed adverse events (AEs) were mild, transient and resolved without medical intervention. Gastrointestinal AEs were more common with formulations containing MCT. Constitutional (lethargy, hypothermia), neurologic (ataxia) and ocular (protrusion membrana nictitans) AEs were more common with oils containing THC (CBD/THC and THC oils).

4. The findings support the safety and tolerability of CBD in the formentioned species. This placebo-controlled escalating dose study, which delivered up to 30.5 mg/kg CBD in an MCT oil matrix, showed oral administration of CBD to be generally well tolerated by cats with no detrimental changes in CBC and clinical chemistry. Importantly, as compared with formulations containing THC, CBD oil was associated with the fewest number of constitutional, neurologic and ocular AEs and the fewest number of behavioral changes.

For further information: https://doi.org/10.1177/1098612X211004215

Clinical Trials - Safety in Cats and Dogs - 2019

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.

Making The Vet Visit Better For Your Cat

Cats are the most popular pets, but you sure wouldn’t know it by looking around the veterinarian’s waiting room. A recent Bayer Veterinary Care Usage Study revealed a third of pet cats did not see a veterinarian in the preceding year at all. The biggest reason cats

are shortchanged when it comes to their health is that people don’t like catching them, putting them in carriers, and dealing with the difficult behavior of fearful cats. Cats territorial instincts and lack of socialization causes them to be become stressed in most situations

where they are handled by unfamiliar people in an unfamiliar setting. When cats become stressed, their natural coping mechanism is to hide or retreat. They will exhibit aggressive behavior as a last resort. So what can be done?

Some Clinics Are Becoming More Cat Friendly

The lack of preventive care for cats means making these pets happier has become a high priority for many veterinarians. Veterinary behaviorists have been helping veterinarians design facilities and protocols to make cat visits less stressful for all, including pet owners,

and hospital staff. "When I’m practicing, I wear so much of the synthetic cat pheromone called Feliway (a version of feline facial pheromones, which relax cats) that it’s more like aftershave to me." says DR. MARTY BECKER DVM. Some clinics now are employing the Fear Free approach, there are classes and certifications that pet owners and Veterinary professionals can get to help their pets stay Fear Free traveling to , during, and after Vet visits. Visit fearfree.com to find out more.

What You Can Do

As veterinarians work to make their practices fear free and feline friendly, there’s a lot you can do to help your cat relax when it’s time to see the doctor. The American Academy of Feline Practitioners offers new guidelines. Here are the main points.

1. Get your cat used to being handled. Be patient and build up your cat’s tolerance for handling. Make sessions short and reward your cat with treats or the kind of petting she enjoys, such as under the chin.

2. Choose a cat-friendly carrier. Find a carrier that opens from the front and top or that opens from the front and unclips easily to allow the entire top to come off so the cat can remain on her bedding in the bottom part.

3. Make your cat’s carrier part of the furniture. If the only time your cat sees a carrier is when he’s headed to the vet, he can’t relax inside. Leave the carrier out and place soft bedding inside. If your cat likes treats, give them to him inside the carrier. Spray Feliway liberally in the carrier. It’s kumbaya in a can.

4. Locate your cat the day before a veterinary visit and don’t let him out to disappear. Let the vet’s office know in advance that your cat is uncomfortable with veterinary visits so they can prepare.

5. If your cat has freaked out at the veterinary office before, ask your veterinarian for medication to calm your cat’s anxiety. There are a variety of products that may calm your cat prior to the appointment, some of these include prescription medication and calming

supplements that include chamomile, CBD extract, and melatonin. Always research thoroughly or ask your Veterinarian before giving your pet anything. If your cat becomes car sick, discuss a medication for that as well.

6. Make sure the carrier is belted safely into your car to minimize movement, and put a towel over the carrier to block the view.

7. Try to remain calm and positive. Your anxiety will make your cat’s worse.

Don't give up and don't get discouraged, you and your cat will get through this stressful time, and you will definitely figure out the things that work best for your cat before, during and after the vet visits. Just be patient with yourself and your cat and it will all come together

in the end! You got this, I believe in you!