When and why: The CBD debate

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Cannabidiol (CBD) and tetrahydrocannabinol (THC) are fairly hot-button topics in veterinary medicine that are difficult to unpack, with no distinguishable gray area—or so I thought. Historically, I always seem to encounter either the die-hard “holistic” believers or their antipode, the “gold standard Western medicine practitioners.” However, in recent years I have learned there are many “closet supporters” of CBD who find it difficult to openly endorse as a legitimate treatment modality because of either lack of clinical understanding or fear of legal ramifications.

As a CBD user who has experienced quantifiable results, I firmly believe there is a place for CBD in veterinary medicine that does not have to be limited to holistic practices. After all, anyone working in emergency medicine is likely familiar with Yunnan Baiyao, a traditional Chinese medicine used in hemorrhagic cases for its presumed hemostatic qualities. All that being said, this is my attempt at addressing the CBD debate.

Cannabis: A basic understanding

To understand when and why CBD is appropriate to discuss or use in veterinary medicine, we must first understand what it is. This requires a general understanding of the cannabis plant. CBD and THC are phytocannabinoid derivatives of the cannabis species.¹ Cannabis is an umbrella term for any hemp or marijuana plant with a THC concentration that has not been quantified; marijuana is cannabis with a determined THC concentration greater than 0.3%; and hemp is cannabis or any part of the plant with a determined THC concentration less than 0.3%.² The Cannabaceae family can be broken down into the species Cannabis sativa and subspecies Cannabis indica and Cannabis ruderalis.²

Although the cannabis community has created a perception that one species is known for higher concentrations of THC over CBD and vice versa, concentrations of either can vary by species and the chemical makeup is greatly affected by how the particular strain is grown. In actuality, the differences between the species largely come down to where the plant originated and the general appearance (eg, plant size and leaf shape).³

The endocannabinoid system

As mentioned, CBD is a phytocannabinoid, which acts on the endocannabinoid system (ECS). The ECS exists within humans and animals, vertebrates and invertebrates alike, and regulates functions in nearly every organ system throughout the body. It consists of G protein-coupled cell-membrane receptors and endogenous cannabinoid ligands, commonly referred to as endocannabinoids.² The receptors most important in understanding the use of cannabis in medicine are cannabinoid receptors 1 and 2 (CB1R and CB2R). CB1R is found mainly within the central and peripheral nervous systems with some general distribution throughout the body, whereas CB2R is found mainly within the immune system.⁴

Canines specifically have been found to have a greatly increased number of CB1R within the cerebellum and brain stem compared with humans, which due to the preferential binding of THC to these receptors accounts for the pronounced clinical signs that we see with marijuana toxicosis.⁵ CBD interacts with receptors quite differently than THC does.

CBD has a weak affinity for receptors but can cause some antagonist activity at CB1R and inverse agonist activity at CB2R.⁴ In humans, this inverse agonist activity has been shown to reduce some of the psychoactive adverse effects (AEs) of THC when used in conjunction with CBD, and is known as the entourage effect.⁵ In veterinary medicine, THC is not a treatment option, but that does not mean CBD cannot be.

The evidence

We know what CBD does on a chemical level, but what is important is the quantifiable response to consistent use. The FDA has only approved 1 cannabis-derived CBD product for use in human medicine. Epidiolex is used to control seizure episodes associated with Lennox-Gastaut syndrome, Dravet syndrome, and tuberous sclerosis complex.⁶ In clinical trials, it showed an average reduction of seizure activity across the 3 syndromes by 39% to 48% over 14- to 16-week periods.⁶ Outside of prescription use, CBD users tout it for its benefits in controlling pain, appetite and nausea, anxiety and depression, and insomnia, just to name a few. I personally have experienced benefits in controlling chronic pain, anxiety, and shift work-related insomnia. With all of the clinical and anecdotal evidence available in human CBD use and the knowledge that animals have an endocannabinoid system akin to humans, it is fairly reasonable to assume that the benefits of use in veterinary medicine would be similar to those we experience. However, exploration of CBD in veterinary medicine did not gain popularity until very recently.

There have only been a handful of CBD studies in animals, with most of the focus on epilepsy and osteoarthritis. Two notable studies are those conducted by Colorado State University (CSU) and Cornell University. The study conducted by CSU involved the use of CBD to treat canine epilepsy. Although it was a small-scale study, the results were promising with 90% of participants experiencing a decrease in seizure activity⁷ and a median reduction in seizure activity of 33%.⁸

The Cornell study addressed canine osteoarthritis and results showed a reduction of pain and improved mobility in over 80% of the participants, suggesting CBD to be an appropriate adjunct therapy in the treatment and management of osteoarthritis.⁹ In both these studies, minimal AEs were noted with the most significant being an increase in serum alkaline phosphatase.^9,10

A safety study conducted by Canopy Animal Health also indicated that CBD oil is well tolerated in canines, with over 94% of AEs scored as mild and mainly involving gastrointestinal signs and elevated serum alkaline phosphatase.¹⁰ Unfortunately, there is limited study data available on the safety and efficacy of CBD use in felines.

Legality of use in veterinary medicine

As proven in multiple studies, CBD can be an effective, safe therapy for many animals, which begs the question of why more veterinarians are not recommending it. Until very recently, CBD was classified as a Schedule I drug under the Controlled Substances Act (CSA) and therefore federally illegal. The passing of the Agricultural Improvement Act of 2018, known popularly as the 2018 farm bill, removed hemp and hemp-derived products from the definition of marijuana, thereby declassifying it as a scheduled substance under the CSA so long as the plant and products contain less than 0.3% THC.¹¹ However, the hemp bill preserved the United States Food and Drug Administration’s right to regulate any cannabis and cannabis derivatives under the Food, Drug, and Cosmetic Act,¹¹ meaning veterinarians cannot legally prescribe CBD as a treatment protocol and must use diligence when discussing its use with clients.

Additionally, although CBD is now legal at the federal level, there are still 8 states with restrictions regarding sales and use,¹² which adds another layer of complexity when considering its use in veterinary medicine. The only way to safely discuss CBD with a client is to refrain from stating that it is a drug that can treat or cure any particular illness. As with any other unregulated supplement or nutraceutical, the loophole exists wherein we can discuss how it can “support” a particular bodily system or function.

The debate

As part of my own research, I recently polled peers, veterinarians, technicians, and assistants to learn their opinions regarding CBD. I asked 2 questions: Do you believe CBD has a future in veterinary medicine, and why or why not? The responses were overwhelmingly in favor of CBD, feeling that “it can’t hurt and might help.” Some of my peers already use CBD for their own animals mostly for its anxiolytic effects and to support mobility and appetite; a few had experience with successful use in epileptic cases in animals whose seizures were poorly managed with multiple anticonvulsant medications. One person had no opinion in either direction due to lack of experience with it. One was firmly against its use, citing a study suggesting no legitimate benefit in patients with epilepsy and concern about misuse at the hands of owners.

Despite the opinions that CBD does have a future, the support comes with stipulations. The primary concern is that there needs to be appropriate training provided to veterinary professionals and equivalent education to owners to prevent misuse; for example, an owner intentionally using a product containing THC, causing a toxicity case. Having seen a large increase in marijuana ingestion cases following the legalization of recreational use in my state, I tend to agree that the risk increases without proper education. The other concerns surround the potential for owners to put all their hope on CBD as a replacement for Western medicine, the fear of legal repercussions for veterinarians, and the stark lack of supporting clinical evidence, and the risk that clients, in an effort to “cut costs,” will use products from companies that cannot provide Independent Lab Testing for proof of quality, purity, and potency.

Considering all the current information on CBD use in human medicine, the beginnings of research in veterinary medicine, and the changes in legality, I strongly believe it has a future in our field. I did not previously subscribe to the hype and I would refuse to discuss the topic with clients or owners who were seeking support and approval for their decisions to experiment with CBD. But like the field, I have evolved and transitioned from my previously adamant no to a willingness to discuss without making recommendations. Now, I can safely say I am ready to openly advocate for its use if it can improve the quality of life for our patients.

I have found that most clients interested in the properties of CBD are pursuing it as a last-ditch effort, frequently as an adjunct therapy in hospice care or to mitigate the AEs of chemotherapy treatment. These owners have nothing left to lose but their animal companions. They, as well as all pet owners, deserve the opportunity to discuss other options. We exist in this profession for the betterment of our patients and their owners; we have an obligation to seek new and better therapies and right now that means we need to focus more attention on CBD research. For me, there is no debate. I am “Team CBD” all the way.

Janelle Overholser, CVT, is an ICU veterinary technician for BluePearl Specialty and Emergency Pet Hospital. She is a graduate of Penn Foster College and recently returned to school to obtain her BAS degree in veterinary technology. She is passionate about emergency medicine and is pursuing her VTS in ECC.

References

1. Compound summary: cannabidiol. National Center for Biotechnology Information. Updated June 19, 2021. Accessed May 6, 2021. https://pubchem.ncbi.nlm.nih.gov/compound/Cannabidiol
2. American Veterinary Medical Association. Cannabis in veterinary medicine. August 2020. Accessed May 6, 2021. https://www.avma.org/sites/default/files/2021-03/APH-CannabisResources-Report-20201207.pdf.
3. Indica vs. sativa: understanding the differences between weed types. Leafly. September 20, 2018. Accessed May 5, 2021. https://www.leafly.com/news/cannabis-101/sativa-indica-and-hybrid-differences-between-cannabis-types
4. Silver RJ. The endocannabinoid system of animals. Animals. 2019;9(9):686. doi:10.3390/ani9090686
5. The entourage effect: How CBD and THC work together. Healthline. Accessed May 7, 2021. https://www.healthline.com/health/the-entourage-effect
6. Epidiolex. Greenwich Biosciences. Accessed May 13, 2021. https://www.epidiolex.com/about-epidiolex
7. McReynolds T. New study: CBD shows promise for treating canine epilepsy. NEWStat. May 30, 2019. Accessed May 13, 2021. https://www.aaha.org/publications/newstat/articles/2019-05/new-study-cbd-shows-promise-for-treating-canine-epilepsy/
8. McGrath S, Bartner LR, Rao S, Packer RA, Gustafson DL. Randomized blinded controlled clinical trial to assess the effect of oral cannabidiol administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with intractable idiopathic epilepsy. J Am Vet Med Assoc. 2019;254(11):1301-1308. doi:10.2460/javma.254.11.1301
9. Smith D. Cornell University study says hemp oil works for dogs in pain. Cannabis.net. February 14, 2018. Accessed May 12, 2021. https://cannabis.net/blog/medical/cornell-university-study-says-hemp-oil-works-for-dogs-in-pain
10. Vaughn D, Kulpa J, Paulionis L. Preliminary investigation of the safety of escalating cannabinoid doses in healthy dogs. Front Vet Sci. 2020;7:51. doi:10.3389/fvets.2020.00051
11. FDA regulation of cannabis and cannabis-derived products, including cannabidiol (CBD). FDA. Updated January 22, 2021. Retrieved May 1, 2021. https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd#farmbill
12. Keehn J. CBD laws by state 2020 - just the facts [is CBD legal in 2020?]. CBD School. Updated February 23, 2021. Accessed May 12, 2021. https://www.cbdschool.com/cbd-laws-by-state-2020/