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What is the current evidence for CBD in veterinary medicine?

Cannabidiol is considered safe for dogs when given 0.2 to 2 mg/kg orally twice, according to Health Canada

December 12, 2022

By Katherine Kramer, DVM, DAVBP (Canine/Feline), CVA, CVTP, Fear Free Certified

Cannabidiol (CBD) is considered safe for dogs when given 0.2 to 2 mg/kg orally twice, according to Health Canada.

Earlier this year, Health Canada published a report from its Scientific Advisory Committee on Health Products Containing Cannabis. The committee, which included an animal health sub-committee composed of three pre-eminent veterinarians, was tasked with providing “independent scientific and clinical advice to support the Department’s consideration of appropriate safety, efficacy, and quality standards for health products containing cannabis.”

The report1 detailed several findings related to veterinary medicine:

  • Cannabidiol (CBD) is considered safe for dogs when given 0.2 to 2 mg/kg orally twice daily.
  • The only condition in dogs with sufficient safety evidence to warrant the use of CBD is osteoarthritis (OA), as diagnosed by a veterinarian.
  • There is insufficient evidence to recommend the use of CBD in cats, horses, or food-producing animals.
  • There is insufficient evidence to recommend the use of CBD in companion animals for chronic pain, seizures, anxiety, or aggression.

The committee recommended CBD products for dogs be sold only through veterinary clinics. Further, until more information related to safety and efficacy is available, pet owners should consult a veterinarian before giving these products to their pets.

In developing this report, the committee most likely examined scientific papers published before 2021. Cannabinoid research has skyrocketed in recent years, with nearly 4000 papers published in 2021 alone. While most studies involve humans or lab animals, companion animal studies are growing. What follows is a brief overview of the most notable canine and feline studies published in 2021 and 2022.

Canine

Pharmacokinetics and safety

This study, completed by Mars Petcare and the Waltham PetCare Science Institute, investigated the use of CBD (4 mg/kg daily) in dogs for six months. Researchers analyzed CBD concentrations in plasma, feces, and urine. Each subject had a daily quality of life (QoL) survey, with physical exam and a lab panel every two weeks.

Hematology and biochemistry parameters were found to be unremarkable, save for a mild increase in alkaline phosphatase (ALP), which was noted in just over 50 per cent of the subjects (primarily due to an increase in the bone isoenzyme of ALP). The study concluded CBD was well tolerated in healthy dogs.

In a European-based study, the pharmacokinetics (pK) of a single dose of CBD given by an intranasal (20 mg), intrarectal (100 mg), or oral (100 mg) route was investigated. Intranasal administration provided the fasted absorption.

A collaborative effort from the University of Kentucky and Lincoln Memorial University (LMU) veterinary schools, this study investigated the effects of CBD on the canine immune response to a novel antigen. CBD and control groups had similar Immunoglobulin G (IgG) and Immunoglobulin M (IgM) responses to the antigen. The study concluded CBD (5 mg/kg/day) did not appear to have humoral immunosuppressive effects.

Also published by researchers at the University of Kentucky and LMU, this study investigated the effects of a 4.5 mg/kg daily dose of CBD for three weeks on the canine plasma metabolome. CBD was found to alter several metabolites.

Seizures

Funded by ElleVet Sciences, this study investigated the effects of a CBD and cannabidiolic acid (CBDA) supplement given to dogs with refractory seizures. The sample included 14 dogs taking either phenobarbital, potassium bromide, zonisamide, or a combination of these medications.

Six out of the 14 dogs had a 50 per cent reduction in seizures across the 12-week study period, and no changes in anticonvulsant drug concentration were noted. The study concluded the use of CBD/CBDA at a dose of 2 mg/kg every 12 hours was safe and beneficial in reducing seizure episodes when combined with anti-seizure medications.

The veterinary schools of Tufts and Colorado State University (CSU) investigated the pK interactions between CBD and phenobarbital in healthy dogs. While there were variations in the CBD pK results from dogs receiving CBD only or in combination with phenobarbital, there were no significant pharmacokinetic interactions noted. Several subjects experienced mild gastrointestinal signs, hypoxia, or an increase in ALP.

Dermatology

This study, completed by researchers from the University of Bologna in Italy, found an increase in the expression of cannabinoid receptors in dogs with atopic dermatitis (AD). This suggests the endocannabinoid system (ECS) may be a potential therapeutic target for CBD.

In another study from ElleVet Sciences, dogs with atopic dermatitis that received a 2 mg/kg daily dose of a supplement containing an equal amount of CBD and CBDA were found to be less itchy than the study’s placebo group. Cytokine assays were performed, along with a complete blood counts (CBC) and biochemistry panel, which revealed no significant differences in interleukin levels between the test and control group.

A retrospective study of eight cases seen by Japanese veterinary dermatologists, this paper summarizes the findings of dogs with AD that were given titrated doses of a 10 per cent CBD broad spectrum product. Six of the dogs were on combinations of prednisolone, oclacitinib, amoxicillin, or ketoconazole.

All of the dogs exhibited a decrease in pruritus approximately two weeks after starting the CBD supplement without any adverse effects reported.

This in vitro study by researchers at the University of Teramo in Italy noted the ability of a nutraceutical compound containing CBD to reverse the overexpression of key genes of inflammation in canine AD.

Neoplasia

This study from the Ontario Veterinary College (OVC) examined the in vitro effects of CBD, used either as a single agent or in combination with several chemotherapy drugs, on canine transitional cell carcinoma. CBD was noted to reduce cell viability and induce apoptosis. It also appeared to have a synergistic effect with mitoxantrone and vinblastine.

OA

For this study, researchers from the CSU College of Veterinary Medicine worked with 23 client-owned, OA-diagnosed dogs. The animals were divided into two groups—one group received a placebo oil for six weeks, followed by a CBD oil for six weeks, while the second received CBD oil first, followed by the placebo. The subjects were evaluated by gait analysis, accelerometry, and clinical metrology instruments. The study found no significant differences in any parameter between the placebo and CBD groups.

Behaviour

Working with a study group of 24 shelter dogs in Italy, this research found, while it appeared to reduce aggressive behaviour toward humans, CBD did not have a significant effect on other stress behaviours.

This study examined the effects of a daily dose of CBD (up to 4.5 mg/kg daily) on 24 dogs. This dose did not impact the animals’ activity levels and appeared to reduce scratching behaviour.

Endocannabinoids

Published in a collaboration by the veterinary teaching hospitals of Teramo and Bologna, Italy, 33 dogs with gastrointestinal signs were compared to a control group of 30 healthy dogs. Three different endocannabinoids were measured—N-arachidonoylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), and palmitoylethanolamide (PEA).

The study found altered endocannabinoid profiles in dogs with chronic enteropathies, which introduces the possible diagnostic use of endocannabinoid levels.

This study, completed jointly by OVC and Kansas State University, investigated the use of several endocannabinoids as prognostic biomarkers for canine lymphoma. Twenty-six dogs with multicentric B-cell lymphoma and 14 dogs with multicentric T-cell lymphoma were compared to 12 healthy dogs. The cancer dogs had increased levels of the endocannabinoids OEA, AEA, and PEA. Measuring PEA levels showed to be potentially useful as a prognostic biomarker for canine lymphoma.

What about cats?

A veterinary school study by Cornell and the University of Illinois (UI) compared the pharmacokinetics of CBD and CBDA in eight cats. The latter was found to have better absorption. No adverse behaviours or lab abnormalities were noted.

In this study from international cannabis corporation Canopy Growth, 20 healthy cats received titrated doses of either CBD (maximum dose: 30.5 mg/kg), THC (maximum dose: 41.5 mg/kg), or a CBD/THC combination oil (with a radio of 13:8.4 mg/kg, CBD:THC). Adverse effects were noted to be mild and transient. No significant changes were noted on CBC or chemistry panels.

Conclusion

While the increase in companion animal studies and the recommendations from Health Canada’s advisory committee are encouraging, the fact remains that, four years after cannabis legalization in Canada, veterinarians still do not have the legal right to prescribe or dispense cannabis products. Without the right to prescribe, our clients cannot access medical-grade products; instead, they are left to visit legal dispensaries to buy recreational-grade products, which have been proven to be inconsistent and unreliable.

Numerous pet products are easily available, but these are not legal and not regulated. Several unscrupulous companies have secured veterinary product health status (allowed only for products composed of hemp seed), and then either falsely advertise their products as containing phytocannabinoids or, worse, add phytocannabinoids without listing this on the label.

The claim ‘more research’ is needed to support the use of cannabis in animals has been heard by the global scientific community. Although there is a growing body of evidence and the field of veterinary cannabinoid medicine is flourishing, many questions are yet to be answered. Namely, in Canada: When will Canadian veterinarians be allowed to prescribe cannabis to patients, and when will there be a safe, quality controlled veterinary health product? Unfortunately, these questions remain to be seen; however, as we continue to move forward and research persists, one can hope this will lead to a stronger future for our patients.

Katherine Kramer, DVM, DAVBP (Canine/Feline), CVA, CVTP, Fear Free Certified, is an integrative companion animal veterinarian practicing in Vancouver, B.C. She is a member of the Canadian Association of Veterinary Medicine, College of Veterinarians of British Columbia, International Veterinary Acupuncture Society, American Association of Feline Practitioners, and the International Veterinary Academy of Pain Management. She is a past director of the Canadian Association of Veterinary Cannabinoid Medicine. Dr. Kramer is also a co-editor/author of Cannabis Therapy in Veterinary Medicine, the first veterinary textbook in the field of veterinary cannabinoid medicine.

References

1 Health Canada. Review of cannabidiol: Report of the Science Advisory Committee on Health Products Containing Cannabis, 2022 July. https://www.canada.ca/content/dam/hc-sc/documents/corporate/about-health-canada/public-engagement/external-advisory-bodies/health-products-containing-cannabis/report-cannabidiol-eng.pdf

2 Bradley S, Young S, Bakke AM, et al. Long-term daily feeding of cannabidiol is well-tolerated by healthy dogs. Frontiers in Veterinary Science, 2022 Sept. https://doi.org/10.3389/fvets.2022.977457

3 Polidoro D, Temmerman R, Devreese M, et al. Pharmacokinetics of cannabidiol following intranasal, intrarectal, and oral administration in healthy dogs. Frontiers in Veterinary Science, 2022 June. https://doi.org/10.3389/fvets.2022.899940

4 Morris EM, Kitts-Morgan SE, Spangler DM, et al. Feeding treats containing cannabidiol (CBD) did not alter canine immune response to immunization with a novel antigen. Research in Veterinary Science, 2022 March;143:13-19. https://doi.org/10.1016/j.rvsc.2021.12.012

5 Morris EM, Kitts-Morgan SE, Spangler DM, et al. Alteration of the canine metabolome after a 3-week supplementation of cannabidiol (CBD) containing treats: An exploratory study of healthy animals. Frontiers in Veterinary Science, 2021 July. https://doi.org/10.3389/fvets.2021.685606

6 Garcia GA, Kube S, Carrera-Justiz S, et al. Safety and efficacy of cannabidiol-cannabidiolic acid rich hemp extract in the treatment of refractory epileptic seizures in dogs. Frontiers in Veterinary Science, 2022 July. https://doi.org/10.3389/fvets.2022.939966

7 Doran CE, McGrath S, Bartner LR, et al. Drug-drug interaction between cannabidiol and phenobarbital in healthy dogs. American Journal of Veterinary Research, 2021 Nov;83(1):86-94. doi:10.2460/ajvr.21.08.0120. https://pubmed.ncbi.nlm.nih.gov/34727050

8 Chiocchetti R, De Silva M, Aspidi F, et al. Distribution of cannabinoid receptors in keratinocytes of healthy dogs and dogs with atopic dermatitis. Frontiers in Veterinary Science, 2022 July. https://doi.org/10.3389/fvets.2022.915896

9 Wakshlag J, Bowden D, Peters-Kennedy J, Rosenberg A. The effect of a mixed cannabidiol and cannabidiolic acid-based oil on client-owned dogs with atopic dermatitis. Veterinary Dermatology, 2022 May; 33(4):329-e77. https://doi.org/10.1111/vde.13077

10 Mogi C, Yoshida M, Kawano K, et al. Effects of cannabidiol without delta-9-tetrahydrocannabinol on canine atopic dermatitis: A retrospective assessment of 8 cases. The Canadian Veterinary Journal, 2022 April; 63(4):423-426. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8922375

11 Massimini M, Vedove ED, Bachetti B, et al. Polyphenols and cannabidiol modulate transcriptional regulation of Th1/Th2 inflammatory genes related to canine atopic dermatitis. Frontiers in Veterinary Science, 2021 March. https://doi.org/10.3389/fvets.2021.606197

12 Inkol JM, Hocker SE, Mutsaers AJ. Combination therapy with cannabidiol and chemotherapeutics in canine urothelial carcinoma cells. PLOS One, 2021 Aug. https://doi.org/10.1371/journal.pone.0255591

13 Mejia S, Duerr FM, Griffenhagen G, McGrath S. Evaluation of the effect of cannabidiol on naturally occurring osteoarthritis-associated pain: A pilot study in dogs. Journal of the American Animal Hospital Association, 2021 March; 57(2):81-90. https://doi.org/10.5326/JAAHA-MS-7119

14 Corsetti S, Borruso S, Malandrucco L, et al. Cannabis sativa L. may reduce aggressive behaviour towards humans in shelter dogs. Scientific Reports, 2021 Feb. https://doi.org/10.1038/s41598-021-82439-2

15 Morris EM, Kitts-Morgan SE, Spangler DM, et al. Feeding cannabidiol (CBD)-containing treats did not affect canine daily voluntary activity. Frontiers in Veterinary Science, 2021 April. https://doi.org/10.3389/fvets.2021.645667

16 Febo E, Crisi PE, Oddi S, et al. Circulating endocannabinoids as diagnostic markers of canine chronic enteropathies: A pilot study. Frontiers in Veterinary Science, 2021 May. https://doi.org/10.3389/fvets.2021.655311

17 Hay JK, Hocker SE, Monteith G, Woods JP. Circulating endocannabinoids in canine multicentric lymphoma patients. Frontiers in Veterinary Science, 2022 Feb. https://doi.org/10.3389/fvets.2022.828095

18 Wang T, Zakharov A, Gomez B, et al. Serum cannabinoid 24-h and 1-week steady state pharmacokinetic assessment in cats using a CBD/CBDA rich hemp paste. Frontiers in Veterinary Science, 2022 July. https://doi.org/10.3389/fvets.2022.895368

19 Kulpa JE, Paulionis LJ, Eglit GML, Vaughn DM. Safety and tolerability of escalating cannabinoid doses in healthy cats. Journal of Feline Medicine and Surgery, 2021 March; 23(12):1162-1175. https://doi.org/10.1177/1098612X211004215

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