Gaining a deeper understanding of the role and function of the endocannabinoid system in dogs and cats can aid you in talking to your clients about CBD and hemp.

The Endocannabinoid System (ECS) is a major lipid signaling system comprising of endogenous cannabinoids, their receptors, and metabolic enzymes that play a critical homeostatic role in processing and modulating various bodily functions in dogs and cats^1-3. This ubiquitous system mediates a homeostatic balance of the nervous and immune systems in conjunction with other organ systems³. Research suggests that a balanced ECS promotes appetite, sleep, mood regulation and stability, gait, pain perception, memory, body temperature, immunity, reproduction and fertility in both humans and pets.  When ECS is out of balance due to lack of enough endocannabinoids, many negative physical signs are often observed in dogs, including digestive issues (vomiting, irregular bowels, diarrhea), poor appetite, sleep issues, stress, anxiety/fear and aggression, lethargy and lack of activity, poor balance and coordination, pain and inflammation. Targeting the ECS with Phytocannabinoids has been shown to trigger the same physiological effects similar to endocannabinoids, thereby promoting systemic well-being¹.

A look at the terminology

Cannabinoids, endocannabinoids and phytocannabinoids

The three kinds of cannabinoids that bind to the cannabinoid receptors, which activate the ECS, include endocannabinoids, synthetic cannabinoids, and phytocannabinoids⁴.

There are two endocannabinoids; anandamide (AEA) and 2-arachidonoylglyerol (2-AG) that are produced from lipids (fats) in the body⁵. These endocannabinoids are similar but also have a specific role within the Central Nervous System (CNS), including neuromodulator, neuroprotection, modulating anxiety, memory, and learning¹.

Endocannabinoids also have functions beyond the CNS, including the immune system; they interact with the cannabinoid receptors⁶. Phytocannabinoids are plant-based chemicals found in cannabis with limited amounts found in other plants and herbs⁷. Synthetic cannabinoids were developed to interact with the specifications with the ECS⁸.

Cannabinoid receptors

There are two key cannabinoid receptors – cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) – located throughout the body¹. CB1 is known to be psychoactive, neuromodulatory, and a pain receptor found in the brain, fat, liver, skeletal, and muscular tissues⁹. CB2 is responsible for the anti-inflammatory functions located in cells that are responsible for immune function and may also be found in the CNS. CB2 also plays a strong role in immune function¹⁰. CB1 is also expressed on immune cells, so they’re both important but delineated in specific roles.

The role of enzymes

After endocannabinoids finalize their functions, they need to be broken down in the body. This is done by two main enzymes¹¹:

• fatty acid amide hydrolase (FAAH) that breaks down AEA
• monoacylglycerol acid lipase (MGL) that normally breaks down 2-AG

Animal versus human

The animal and human endocannabinoid systems are similar with respect to the cellular processes and organ systems. The major difference is the distribution of the CB1 receptors in dogs compared to humans. Studies have shown the higher number of CB1 receptors in the hind brain structures (cerebellum, brain stem, and medulla oblongata) of canine species when compared to humans¹². THC has a greater affinity for CB1 receptors. Hence, exerting a unique neurological action “static ataxia” when stimulated by THC due to high concentration of CB1 receptors in the cerebellum of canine species¹. The CB₁ and CB₂ receptors are structurally somewhat similar, except for their respective anatomical distribution in the central nervous system and immune system¹. A great deal of data exists on the role of phytocannabinoids in promoting balance of ECS by differential activation of CB1 and CB2 receptors present throughout the body system when administered^1,3,13.

Full and broad-spectrum hemp oil products containing less than 0.3% THC are very beneficial in this case. Therefore, recommended dosage of hemp oil supplementation (based on body weight of feline and canine candidates) needs to be followed.

Backed by science

There is considerable evidence regarding clinical and health benefits from phytocannabinoids in humans. However, there is still little information and lack of sufficient evidence-based studies regarding the same benefits in animals, except for studies performed in experimental laboratory animals. Scientific research evidence clearly shows that ECS is intimately involved in the regulation of most physiological processes in animal systems¹. A balanced ECS tone (the proper functioning of ECS) plays an important role in regulating the neurological, endocrine, musculoskeletal and immune systems through a complex cellular network to ameliorate pain and inflammation, modulate metabolism, support bone health, and promote digestive health^{1, 3, 5, 7, 8, 11}.

Recommending hemp to your patients

ECS plays a direct role in physiological homeostasis, as it regulates nearly every metabolic process in an animal’s body. As backed by science, a well-balanced ECS will encourage favorable conditions in the animal’s body, impacting their ability to self-manage metabolic stress, anxiety, depression, pain, inflammation and support overall health and systemic well-being. When we understand how full and broad spectrum hemp oil interacts with their ECS, we can potentially provide relief from certain health ailments and improve their quality of life.

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¹Silver RJ. The Endocannabinoid System of Animals. Animals (Basel). 2019;9(9):686. Published 2019 Sep 16. doi:10.3390/ani9090686

²Ritter S, Zadik-Weiss L, Almogi-Hazan O, Or R. Cannabis, One Health, and Veterinary Medicine: Cannabinoids’ Role in Public Health, Food Safety, and Translational Medicine. Rambam Maimonides Med J. 2020 Jan 30;11(1):e0006. doi: 10.5041/RMMJ.10388. PMID: 32017686; PMCID: PMC7000163.

³Freundt-Revilla J, Heinrich F, Zoerner A, Gesell F, Beyerbach M, et al. (2018) The endocannabinoid system in canine Steroid-Responsive Meningitis-Arteritis and Intraspinal Spirocercosis. PLOS ONE 13(2): e0187197. https://doi.org/10.1371/journal.pone.0187197

⁴Cabral, G. A., Rogers, T. J. & Lichtman, A. H. Turning Over a New Leaf: Cannabinoid and Endocannabinoid Modulation of Immune Function. J Neuroimmune Pharmacol 10, 193-203, doi:10.1007/s11481-015-9615-z (2015).

⁵Kaur, R., Ambwani, S. R. & Singh, S. Endocannabinoid System: A Multi-Facet Therapeutic Target. Curr Clin Pharmacol 11, 110-117 (2016).

⁶Sulcova, E.; Mechoulam, R.; Fride, E. Biphasic Effects of Anandamide. Pharmacol. Biochem. Behav. 1998, 59, 347–352.

⁷Munro, S., Thomas, K. L. & Abu-Shaar, M. Molecular characterization of a peripheral receptor for cannabinoids. Nature 365, 61-65, doi:10.1038/365061a0 (1993)

⁸Russo, E. B. Beyond Cannabis: Plants and the Endocannabinoid System. Trends in pharmacological sciences 37, 594-605, doi:10.1016/j.tips.2016.04.005 (2016).

⁹Pertwee, R.G. Cannabinoid receptors and pain. Prog. Neurobiol. 63, 569–611 (2001)

¹⁰Turcotte C, Blanchet MR, Laviolette M, and Flamand N. The CB2 receptor and its role as a regulator of inflammation. Cell Mol Life Sci. 73(23): 4449-4470 (2016). doi: 10.1007/s00018-016-2300-4

¹¹Cable JC, Tan GD, Alexander SPH, and O’Sullivan SE. The effects of obesity, diabetes and metabolic syndrome on the hydrolytic enzymes of the endocannabinoid system in animal and human adipocytes. Lipids in Health and Disease, 13; 43 (2014)

¹²Herkenham, M.; Lynn, A.B.; Little, M.D.; Johnson, M.R.; Melvin, L.S.; de Costa, B.R.; Rice, K.C. Cannabinoid receptor localization in brain. Proc. Natl. Acad. Sci. USA, 87, 1932–1936 (1930).

¹³Paula Morales, Dow P. Hurst, and Patricia H. Reggio. Prog Chem Org Nat Prod.103: 103–131 (2017). doi: 10.1007/978-3-319-45541-9_4