Clinical Trials - Preliminary Investigation of the Safety of CBD in Escalating Dosing in Dogs

Dana Vaughn, Justyna Kulpa, and Lina Paulionis

Objective: To determine the safety and tolerability of escalating doses of three cannabis oil formulations, containing predominantly CBD, THC, or CBD and THC vs. placebo in dogs.

Design: Randomized, placebo-controlled, blinded, parallel study.

Animals: Twenty healthy Beagle dogs (10 males, 10 females).

Methods: Dogs were randomly assigned to one of five treatment groups (n = 4 dogs per group balanced by sex): CBD-predominant oil, THC-predominant oil, CBD/THC-predominant oil, sunflower oil placebo, medium-chain triglyceride oil placebo. Up to 10 escalating doses of the oils were planned for administration via oral gavage, with at least 3 days separating doses. Clinical observations, physical examinations, complete blood counts, clinical chemistry, and plasma cannabinoids were used to assess safety, tolerability, and the occurrence of adverse events. Adverse events were rated as mild, moderate and severe.

Results: Of the three cannabinoid oil formulations tested, dose escalation of the CBD-predominant oil formulation was the most tolerated by dogs up to a maximum dose of 640.5 mg CBD (~62 mg CBD/kg) and only mild AEs were experienced. Dose escalation of the CBD-predominant oil formulation was shown to be as safe as placebo and safer than dose escalation of oils containing THC (CBD/THC oil or THC oil). AEs were reported in all dogs across the five groups and the majority (94.9%) were mild. Moderate AEs (4.4% of all AEs) and severe/medically significant AEs (0.8% of all AEs) manifested as constitutional (lethargy, hypothermia) or neurological (ataxia) symptoms and mainly occurred across the two groups receiving oils containing THC (CBD/THC oil or THC oil).

Conclusions and clinical significance: Overall, dogs tolerated dose escalation of the CBD oil well, experiencing only mild AEs. The favorable safety profile of 10 escalating doses of a CBD oil containing 18.3–640.5 mg CBD per dose (~2–62 mg/kg) provides comparative evidence that, at our investigated doses, a CBD-predominant oil formulation was safer and more tolerated in dogs than oil formulations containing higher concentrations of THC. Of the three cannabinoid oil formulations tested, dose escalation of the CBD-predominant oil formulation was the most tolerated by dogs up to a maximum dose of 640.5 mg CBD (~62 mg CBD/kg) and only mild AEs were experienced.

Citations: https: //www.ncbi.nlm.nih.gov/pmc/articles/ PMC7029731/

Front Vet Sci. 2020; 7: 51

Clinical Trial Pharmacokinetics, Safety and Clinical Efficacy of CBD Treatment

Pharmacokinetics, Safety and Clinical Efficacy of Cannabidiol Treatment of Osteoarthritic Dogs. July 2018

1-The objectives of the study were to determine basic oral pharmacokinetics and assess safety and analgesic of a cannabidiol (CBD) based oil in dogs with osteoarthritis (OA).

2- Single-dose administrations were performed using two different doses of CBD enriched (2 mg and 8 mg/kg) oil. The CBD extraction was reconstituted into an olive oil base. A randomized placebo controlled, veterinarian and owner blinded cross over study was conducted. Each dog received each of the two treatments with a 2-week wash-out period.

3- Twenty-two client owned dogs with clinically and radiographically confirmed evidence of osteoarthritis were recruited for the study. Sixteen of these dogs completed the study. Dogs were removed due to osteosarcoma (placebo oil), gastric torsion (placebo oil), prior aggression issues (CBE oil), kidney insufficiency (CBD oil), reoccurring pododermatitis (placebo oil) and diarrhea (placebo oil).

3- At each visit each dog was evaluated by a veterinarian based on a scoring system as well by its owner (canine brief pain inventory and Hudson activity scale) and blood was collected to repeat complete blood counts and chemistry analysis at weeks 2 and 4 for each treatment.

4- Pharmacokinetics demonstrated that CBD half-life of elimination median was 4.2 hours for the 2 mg dose and 4.2 hours for the 8 mg dose.

5- There were no significant difference in subjective veterinary lameness and weightbearing capacity. There were no observed side effects.

To view this clinical trial: www.frontierin.org/articles/10.3389/fvets.2018.00165/full

A Report of Adverse Effects Associated with the Administration of Cannabidiol in Healthy Dogs

Journal of the American Holistic Veterinary Medical Association (JAHVMA). Article first appeared in Volume 52, Fall Issue, 2018.

1) The purpose of this study was to determine the tolerability of cannabidiol (CBD) by healthy dogs. The scientists hypothesized that CBD would be tolerated in a healthy population of dogs. A group of 30 healthy Beagle dogs were randomly assigned to receive CBD in the form of microencapsulated oil beads (capsule), CBD-infused oil, or CBD-infused transdermal cream at a dose of 10 mg/kg/day or 20 mg/ kg/day for 6 weeks. Complete blood counts, chemistry panels, urinalysis, and bile acids were performed at 0, 2, 4, and 6 weeks.

2) Clinically significant results were recorded as binary data indicating the presence or absence of the clinical outcome. Contingency tables were constructed for each of the analyses; and the Fisher's exact test was used to evaluate the significance of association between the formulations at each time point, and between the time points within each formulation for both doses of CBD. A P value of 0.05 was used to determine statistical significance.

3) Throughout the 6-week study period, gastrointestinal upset was the most frequently recorded adverse clinical sign. All of the dogs in the study developed diarrhea, and 6/30 (20%) dogs had single episodes of vomiting. The dogs that vomited were in the groups that received CBD orally in the form of capsules.

4) Erythematous pinnae was the second most common adverse clinical sign reported at week 2 and 4. A mild erythematous reaction of the pinnae occurred in 11 dogs (36%), 9 of whom belonged to the group that received the transdermal cream.

5) Limitations of this study include the lack of a control group and the short duration of the study period. Each dog served as its own control but an actual control group would have helped to confirm if adverse effects were secondary to CBD versus other causes, such as being housed in an unfamiliar setting or eating unfamiliar food especially with regard to the diarrhea.

Reference

https://www.ahvma.org/wp-content/uploads/AHVMA-2018-V52-CannabisAdverseEffects.pdf