Osteoarthritis: Daily CBD Treatment to Reduce Canine Osteoarthritis Pain

A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain

D. Verrico, S. Wesson, V. Konduri, C. J. Hofferek, J. Vazquez-Perez, E. Blair, K. Dunner Jr, P. Salimpour, W. K. Decker, M. M. Halpert                 

2021

KEY TAKEAWAYS:

• Joint destruction in arthritis is driven by a series of inflammatory molecules, of which TNF-α is a major player
• CBD induced a 97% reduction in the secretion of TNF-α in human cells
• Influx of immune cells was reduced by more than 80% after topical CBD application, whereas TNF-α production was reduced by 50%.
• Cannabidiol treatment significantly reduced the development of edema 
• When injected into mice models, CBD caused an increase of anti-inflammatory molecules

OBJECTIVES & HYPOTHESIS → Pain is the primary symptom in osteoarthritis (OA); yet, current treatments are not curative and can be accompanied by significant adverse effects. The joint destruction in arthritis is driven by pathologic inflammatory molecules, including TNF-α, IL-1b, IL-6, IL-17, and IL-21. In addition, pain, inflammation, and joint destruction are mediated by various subsets of immune cell types. As such, the present study aimed to validate whether CBD might positively impact the development and progression of this disease., having as main objective evaluating CBD’s ability to modulate the production of proinflammatory molecules, both in vitro and in vivo.

METHODS → For the in vitro determination of CBD impact on pro-inflammatory molecules, 4 cell types (2 from mice and 2 humans) were isolated. Lipopolysaccharide (LPS) or staphylococcal enterotoxin B (SEB) was added to the cells in order to create an inflammatory environment and later CBD was added. For the in vivo study with mice, 342 subjects were subjected to 2 different inflammation models, the first local and the second generalized. In the first model, croton oil was topically applied to the right ear and 2 hours later vehicle or 100 mL of 10 mg/mL CBD oil was topically applied to swollen and control ears. In the second model, LPS was administered internally and 2 hours after, mice were injected with CBD (1, 10, or 100 mg) or topically administered either CBD (100 mg) or 18.3% methyl salicylate/16% menthol. 

RESULTS → Both LPS and SEB provoked elevations in TNF-α secretion in the cell populations. Application of 100 ng/mL CBD and LPS induced a 42% (human blood cells) to 97% (human immune cells) reduction in TNF-α secretion. Similarly, application of 100 ng/mL CBD in conjunction with SEB induced a 55% (mouse immune cells) to 63% (human immune cells) reduction in TNF-α secretion. These results support the anti-inflammatory potential of CBD. 

Graphic 1: CBD reduces hallmarks of arthritis-related inflammation in vitro. RAW267.4 Macrophage and Mouse Splenocyte are immune mouse cells. THP-1 is a human immune cell and PBMC are peripheral blood mononuclear cells also involved in the immune system.                

Moving to the in vivo local inflammation model, the administration of croton oil induced an inflammatory reaction that includes edema, erythema, immune cells influx, and the production of TNF-α 1 mg of CBD was topically applied. MPO activity (proxy for immune cells influx) in the treated ear was reduced over 80% with concurrent application of CBD. Circulating TNF-α was decreased by 50% after CBD application in comparison with croton oil alone. Cannabidiol treatment also significantly reduced the development of edema. In the systemic (or generalized) inflammation model, administration of LPS induced an inflammatory response with increased expression of TNF-α and IL-6. 2 hours later, mice were injected with increasing doses of CBD (1, 10, or 100 mg) or topically administered with a single CBD dose of 100 mg. Both internal and topical administration of CBD reduced circulating TNF-α and IL-6 levels in a dose-responsive fashion. Moreover, internal administration of CBD alone increased levels of IL-10 (an anti-inflammatory molecule) in the absence of an inflammatory stimulus. Circulating immune cells levels were also reduced up to 60% among LPS-treated mice to which CBD had been administered.