How CBD interacts with an animal’s endocannabinoid system to impact health outcomes

How CBD interacts with the endocannabinoid system in animals

Unravelling the intricacies of the endocannabinoid system (ECS) in dogs and cats can help understand the role of endocannabinoids and CBD oil treatments for pets.

If you haven’t heard of this ubiquitous system before, the endocannabinoid system or ECS is found in virtually all animals, from mammals to mussels; most creatures on land and sea contain an ECS that influences innumerable biological and physiological functions.

What is the endocannabinoid system?

The ECS is an integral and widely distributed signalling system that plays a critical role in maintaining homeostasis across each other body system. It mediates messages and modulates responses in key areas such as the immune, cardiovascular and nervous systems.

There is evermore research being done surrounding the role of the ECS in terms of appetite regulation, sleep, pain perception, immunity, fertility, memory, cognition, mood and much more. In both pets and humans, the ECS can become out of balance due to stress, diet, lifestyle, illness and other factors.

By using phytocannabinoids such as CBD to influence ECS processes, vets can offer treatment for pets that supports their body’s innate capacity to return to a dynamic state of equilibrium.

There are three key components of the ECS that give us a broad understanding of its actions and mechanisms. They are the endocannabinoids, also referred to as ligands, which bind to receptors and lastly the enzymes that metabolise endocannabinoids.

Endocannabinoids

There are two primary endocannabinoids anandamide and 2-archidonyl glycerol (2-AG), plus numerous others for which research has not yet elucidated their full value and potential actions.

2-AG has a greater binding capacity for cannabinoid receptors 1 and 2 than anandamide does and therefore has vast influence over the nervous system, inflammatory and metabolic pathways. 

Anandamide, which has a lesser affinity for cannabinoids receptors also binds to a number of sites such as TRPV and PPAR receptors throughout the body that directly or indirectly affects a range of ECS processes.

In binding to various receptors, endocannabinoids trigger actions in other body systems, creating a cascade of effects. For example, when endocannabinoids such as anandamide or palmitoylethanolamide bind to TRPV1 receptors they modulate pain signals and may provide pain relief in conditions like arthritis.

Cannabinoid receptors

Thus far there have been two specific cannabinoid receptors detected, CB1 and CB2. There are a number of other receptors that play separate roles in the body, yet also contribute to the ECS symphony.

CB1 receptors are expressed in greatest concentrations in the central nervous system, with particular areas of density within the brain that vary amongst different species. They are involved in neuropathic pain sensation, regulation of appetite hormones, memory and mood.

CB2 receptors are more often seen in the immune and gastrointestinal systems where they are involved in inflammatory processes.

By no means are the above actions exhaustive. Both cannabinoid receptors are expressed systemically through the body and can trigger or influence processes related to reproduction, sleep cycles, digestive motility, heart rhythm, bone density and more.

Enzymes that breakdown endocannabinoids

For each main endocannabinoid, there is an associated enzyme that catalyzes its breakdown. For anandamide that is FAAH, and for 2-AG the enzyme is MAGL.

Certain genetic, dietary and environmental factors can influence the activity of these enzymes which can result in lower than optimal levels of endocannabinoids. Low or dysregulated synthesis of endocannabinoids can lead to varied symptom presentations depending on the human, pet or other animal.

The role of endocannabinoids in dogs and cats?

Much like in humans, endocannabinoids play a key role in the release of neurotransmitters, regulation of digestion, sleep, mood and inflammation for our beloved pets. They are constantly being created on-demand to suit the needs of your cat or dog to maintain physiological balance. 

If the endocannabinoid system is out of balance due to stress, injury or any number of factors, symptoms may arise. There are researchers dedicated to investigating whether endocannabinoid deficiency can manifest conditions in humans such as fibromyalgia, irritable bowel disorders, mood and inflammatory conditions. 

For our pets, changes in optimal levels of endocannabinoids might result in signs such as digestive disturbances, changes to behaviour (aggression, fear, melancholy) or pain sensitivity.

Although humans and our furry counterparts both have endocannabinoid systems, the distribution of receptors and levels of endocannabinoids can be very different. This affects the way their bodies process cannabis medicines and in turn how cannabinoids are prescribed to pets.

Endocannabinoids, medical cannabis and CBD for pets 

Engaging ECS processes through the use of medical cannabis and CBD oil may assist in rebalancing dysregulated pathways by promoting the synthesis of endocannabinoids or mimicking their actions. The endocannabinoid system in dogs is currently receiving the most attention in clinical research outside humans. 

In humans, medical cannabis is considered to have a relatively acceptable safety profile given that cannabinoid receptors are not found in areas of the brain stem and medulla that control vital autonomic functions such as proprioception, heart rate and breathing.

Unlike us, dogs do exhibit CB1 receptors in large numbers in these regions of the brain which is why they can have neurological reactions to high doses of THC. Static ataxia in dogs from THC intoxication results in changes to balance, gait, heart rhythm or vomiting.

THC is not prescribed to pets in Australia however, there is some research suggesting very low doses of THC alongside CBD may be beneficial in treating pets.

Across both cats and dogs, CBD is much safer and well indicated for a range of conditions. Again, there is great interest in cannabinoid therapy and dogs at present, with research on cats limited to a few safety trials.

For dogs with epilepsy, it is theorised that CBD indirectly acts on cannabinoid receptors, up or downregulating pathways that influence the ECS to reduce seizures via calming neuroexcitability and protecting neurons in the brain.

There is much more to uncover about endocannabinoids, the ECS and their impact on diseases as well as how influencing these complex processes can help alleviate symptoms and support wellness.

For now, we know CBD to have a range of relevant actions for our pets including pain relief, anti-seizure and anti-inflammatory properties. Learn more about how to prescribe CBD or whether it might be appropriate for your pet get in touch with one of our team at [email protected] with any questions.

By Jessica Kindynis

REFERENCES

 

De Briyne, N., Holmes, D., Sandler, I., Stiles, E., Szymanski, D., Moody, S., Neumann, S., & Anadón, A. (2021). Cannabis, Cannabidiol Oils and Tetrahydrocannabinol-What Do Veterinarians Need to Know?. Animals : an open access journal from MDPI, 11(3), 892. https://doi.org/10.3390/ani11030892
 Deabold, K. A., Schwark, W. S., Wolf, L., & Wakshlag, J. J. (2019). Single-Dose Pharmacokinetics and Preliminary Safety Assessment with Use of CBD-Rich Hemp
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Freundt-Revilla, J., Kegler, K., Baumgärtner, W., & Tipold, A. (2017). Spatial distribution of cannabinoid receptor type 1 (CB1) in normal canine central and peripheral nervous system. PloS one, 12(7), e0181064. https://doi.org/10.1371/journal.pone.0181064
McGrath, S., Bartner, L. R., Rao, S., Packer, R. A., & Gustafson, D. L. (2019). 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. Journal of the American Veterinary Medical Association, 254(11), 1301–1308. https://doi.org/10.2460/javma.254.11.1301
 Brioschi, F. A., Di Cesare, F., Gioeni, D., Rabbogliatti, V., Ferrari, F., D’Urso, E. S., Amari, M., & Ravasio, G. (2020). Oral Transmucosal Cannabidiol Oil Formulation as Part of a Multimodal Analgesic Regimen: Effects on Pain Relief and Quality of Life Improvement in Dogs Affected by Spontaneous Osteoarthritis. Animals : an open access journal from MDPI, 10(9), 1505. https://doi.org/10.3390/ani10091505

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