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Endocannabinoids May Play a Role in Canine Osteoarthritis


The presence of endocannabinoids in canine arthritic knee joints opens the door for new approaches to treating this painful condition.

Osteoarthritis (OA) is a common and painful orthopedic condition in dogs. During OA, a complex interaction of multiple factors (eg, metabolic, biochemical) and active inflammation results in loss of articular cartilage and eventual bony spur development. Because “NSAIDs do not always provide adequate pain relief and may have severe side effects, there is an urgent need for the development of treatments for arthritis,” wrote the authors of a recent BMC Veterinary Research paper on canine OA.

The endocannabinoid system (ECS) modulates inflammation, suggesting a potential role in OA pathophysiology and treatment. The ECS comprises two cannabinoid receptors (CBR1, CBR2) and their endocannabinoid (EC) ligands—arachidonoyl ethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). AEA and 2-AG are produced when needed by various cell types and have very rapid and specific biological activity. Interestingly, several fatty acids (oleoylethanolamide [OEA], palmitoylethanolamide [PEA]) modulate ECS activity but do not bind to cannabinoid receptors, earning them the term “entourage compounds.”


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Because there has been little veterinary research on ECS, the current study’s authors sought to characterize the presence of ECs and entourage compounds in dogs with OA.

Sample Collection

The investigators obtained synovial fluid samples from 10 adult dogs with radiologic evidence of OA in 1 knee joint. For each dog, samples were collected from the arthritic and contralateral healthy knee joint during surgical anterior cruciate ligament reconstruction. The authors then performed synovial fluid cytology and measured levels of AEA, 2-AG, OEA, PEA, and the pro-inflammatory cytokines TNFα and IL-1 beta.

Analysis Results

Compared with healthy synovial fluid, OA synovial fluid had significantly higher levels of neutrophils, mononuclear cells, AEA, and 2-AG. The authors noted that, in a previous human study, AEA and 2-AG were found only in patients with OA and not in healthy patients. In the current study, AEA and 2-AG may have been present in the healthy knees due to early, undiagnosed OA or inflammation caused by altered weight bearing.

Levels of OEA, PEA, TNFα, and IL-1 beta were similar between synovial fluid samples of healthy dogs and dogs with OA. Their presence in the healthy synovial fluid samples may also be explained by early OA or altered weight bearing.

Moving Forward

For the future, the authors proposed larger studies to further define the role of the ECS in canine OA pathophysiology and evaluate the innovative therapeutic potential of cannabinoids in veterinary medicine.

Dr. JoAnna Pendergrass received her Doctor of Veterinary Medicine degree from the Virginia-Maryland College of Veterinary Medicine. Following veterinary school, she completed a postdoctoral fellowship at Emory University’s Yerkes National Primate Research Center. Dr. Pendergrass is the founder and owner of JPen Communications, a medical communications company.

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