Our pets have CB-1 receptors in the brain and CB-2 receptors in the body, their natural messenger cannabinoids are anandamide and 2-AG, anandamide's. Let's talk about the endocannabinoid system in cats and dogs and how CBD oil works with this system to keep dogs and cats — and humans. Just like their human companions, animals like dogs, cats, and horses have an endocannabinoid system responsible for maintaining balance.
Endocannabinoid Dogs Systems Have
CB2 is detected at low levels in resting cells, while it is present at high levels in activated macrophages [ 5 , 89 ]. Endocannabinoids have been shown to downregulate inflammation in numerous experimental models [ 20 — 26 ]. Activation of the cannabinoid system has been linked to decreased inflammatory cell recruitment and enhanced anti-inflammatory cytokine production [ 18 ]. Evidence shows that exogenous application of AEA and 2-AG exerts anti-inflammatory effects by decreasing the production of inflammatory mediators [ 19 ].
The rapid activation of cannabinoid receptors by endocannabinoids after SCI is thought to be an endogenous protective response [ 48 ]. In another study, Arevalo-Martin and colleagues showed that one single injection of 2-AG 30 minutes after the induction of the lesion, protects the white matter from secondary damage, reducing the lesion expansion and myelin loss [ 46 ], while CB1 and CB2 antagonists increased myelin damage [ 48 ].
Although several studies support endocannabinoids as anti-inflammatory mediators, several in vitro and in vivo experiments have reported a pro-inflammatory role of the endocannabinoid system in the development of inflammation [ 18 ]. These pro-inflammatory effects have been associated with enhanced leukocyte recruitment and activation, production of reactive oxygen species and release of pro-inflammatory cytokines [ 1 , 58 , 59 , 65 , 95 , 96 ].
Nonetheless, most of these pro-inflammatory effects attributed to endocannabinoids involve 2-AG, but not AEA [ 18 ]. Indeed, AEA is a potent anti-inflammatory endocannabinoid and acts practically on all cell subsets except natural killer cells and B cells, while 2-AG exerts both pro- and anti-inflammatory effects which seem to be strictly dependent on cell type [ 97 ]. The endocannabinoid system response in inflammation is indeed dependent on type and state of the disease. While CB2 receptor activation in general mediates immunosuppressive effects limiting inflammation and being associated with tissue damage in several pathological conditions, in some disease states activation of the CB2 receptor may enhance or even trigger tissue damage [ 84 ].
In physiological conditions, the endocannabinoid production by neurons is high and in microglia low [ 98 ]. In diseased CNS tissue with an activated immune system the cell-specific expression profile of cannabinoid receptors changes, resulting in higher expression of CB2 receptors in activated microglia [ 16 , 98 ], which can secondarily activate astrocytes leading to further induction of expression of inflammatory factors [ 5 ].
Such an upregulation on activated microglia cells was also seen in the evaluated canine inflammatory CNS diseases and could be the reason for the excessive immune response in SRMA. As the disorder progresses, the blood brain barrier BBB becomes partially disrupted and blood macrophages, B cells, T cells, natural killer cells and other infiltrating leukocytes start upregulating CB2 [ 5 , 42 , 93 ].
Although the initial enhancement of the endocannabinoid system has been proven to have an endogenous protective response and attempts to control inflammation, as the disease progresses, a later dysregulation of the endocannabinoid system during neuroinflammation leads to increased CB2 receptor expression, excessive endocannabinoid production leading to an exacerbated inflammatory response.
Thus, both CB2 agonists and antagonists might be beneficial in counteracting the inflammatory consequences depending on the disease phase [ 42 ].
The present study revealed an upregulated endocannabinoid system in canines with inflammatory CNS diseases, highlighting the endocannabinoid system as a potential target for treatment of inflammatory CNS diseases.
Furthermore, dogs with eosinophilic pleocytosis showed higher level of ECs than those with neutrophilic pleocytosis. Such an upregulation of AEA and 2-AG together with an overexpression of CB2 receptors may indicate a dysregulation of the endocannabinoid system and may be involved in the inflammatory response. Therefore, the development of new anti-inflammatory treatment strategies in canine CNS inflammation should involve the EC system.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. National Center for Biotechnology Information , U. Published online Feb 6. Author information Article notes Copyright and License information Disclaimer. The authors have declared that no competing interests exist. Received Nov 25; Accepted Oct This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract Endocannabinoids ECs are involved in immunomodulation, neuroprotection and control of inflammation in the central nervous system CNS. Introduction In the last decades an increasing interest emerged in the use of derivatives of the plant Cannabis sativa and Cannabis indica commonly known as Marijuana to treat a variety of disorders both in humans and animals.
Materials and methods Serum and cerebrospinal fluid samples A total of 41 cerebrospinal fluid CSF samples and 36 serum samples were retrospectively analyzed. Animals and tissue samples A total of 8 dogs with SRMA, 2 dogs with confirmed IS, and 5 healthy controls were included in the immunohistochemical evaluation. Open in a separate window. Immunohistochemistry Immunohistochemistry IHC was performed using the avidin-biotin-peroxidase complex ABC method as previously described [ 36 , 40 ].
Spatiotemporal localization of CB2 receptors in healthy dogs Cannabinoid receptor type 2 immunoreaction was detected in spleen and liver samples of healthy dogs serving as positive controls.
CB2 immunoreaction in spleen and liver of a healthy control dog. Spatiotemporal localization of CB2 receptors in IS lesions On thoracic spinal cord sections of dogs with IS, strong CB2 expressing leucocytes, predominantly lymphocytes, plasma cells and macrophages but also eosinophils and neutrophils were found adjacent to the parasite or the parasite tracts, accompanied by severe, multifocal to coalescing necrosis and hemorrhage but also within the subarachnoidal space Fig 5B, 5C and 5D.
Immunohistochemistry of anti-CB2 antibody in spinal cord lesions of dogs with intraspinal spirocercosis. Discussion In the present study, it could be proven that the endocannabinoid system is involved in two different canine inflammatory CNS diseases. Conclusions The present study revealed an upregulated endocannabinoid system in canines with inflammatory CNS diseases, highlighting the endocannabinoid system as a potential target for treatment of inflammatory CNS diseases.
Data Availability All relevant data are within the paper. Miller AM, Stella N. CB2 receptor-mediated migration of immune cells: British journal of pharmacology.
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Endocannabinoids are produced naturally by humans and most other animals including mammals, birds, fish, and so on. Phytocannabinoids are produced in plants, with cannabis flowers being the most prolific producer. As it turns out, the phytocannabinoids found in CBD oil can mimic certain endocannabinoids.
They also produce unique effects of their own. So, what is it that these two types of cannabinoids are actually doing in the body? Many cells in the human body have receptors of their surface that interact with cannabinoids. As mentioned, cannabinoids are relaying instructions from the brain to all the major organs and the immune system at a cellular level.
The way this works is that if the brain detects some kind of imbalance, it produces particular cannabinoid molecules to relay particular behavioral instructions to individual cells and organs. The process is meant to bring the system back into balance. For example, when the brain detects danger, it produces signaling molecules that get an animal amped up and prepared to fight or flee. Heart rate and breathing increase, senses and emotions are heightened, and so on.
When the danger passes the brain produces another set of signaling molecules that tells bodily systems to calm back down. If this system is out of balance, it can cause chronic anxiety issues. The same goes with sleep patterns, digestive activity, inflammatory response, immune response, and on and on. The way CBD fits into all of this is that it mimics the effects of certain endocannabinoids that are involved in all these processes such as reducing anxiety, keeping inflammation in check and many, many more.
Endocannabinoid System in Dogs & Cats Explained
Anxiety, joint pain, skin conditions, cancer if your dog has any of these health concerns, Dogs have the same endocannabinoid system (ECS) as humans. Additionally, 3 serum and 7 CSF samples from seven dogs affected with IS presented to the Koret School of Veterinary. Endogenous cannabinoids use these receptors as part of a signaling system that Dogs are reported to have a higher number of cannabinoid receptors in the.