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Cannabidiol’s Intriguing Role in Joint Health

By May 15, 2019CBD

By Chris D. Meletis, ND

For thousands of years, cannabis has been used by people suffering from pain, including joint-related disorders.1 Today, joint pain is the largest medical reason for requesting use of the drug.1  In comparison, it is only relatively recently that researchers have started to investigate cannabidiol (CBD), a non-psychoactive component of cannabis, for its beneficial effects on the joints. Many of the preclinical findings confirm what I’ve witnessed in my clinical practice—that CBD is likely an effective option for patients with arthritis.

The Endocannabinoid System and Joint Health

 Although an extensive discussion of the endocannabinoid system is outside the scope of this article, it is necessary to recap some basic functions of this system to understand its effects on pain. The endocannabinoid system comprises the cannabinoid receptors 1 and 2 (CB1 and CB2), their endogenous ligands known as endocannabinoids, and the enzymes responsible for their synthesis and degradation. The two primary endocannabinoids are anandamide and 2-arachidonoylglycerol (2-AG). It has recently been discovered that other receptors such as transient receptor potential cation channel subfamily V member 1 (TRPV1), peroxisome proliferator-activated receptor alpha (PPARα), and G-protein coupled receptor 55 (GPR55) play an critical role in the endocannabinoid system.2

Although CBD is a phytocannabinoid, its effects on joint health and inflammation are not primarily mediated directly through the traditional endocannabinoid receptors CB1 and CB2. Rather, it acts through PPARα, TRPV, and G-protein coupled receptors.3 CBD’s modulation of the endocannabinoid system also occurs through its ability to inhibit FAAH, the enzyme that breaks down the endocannabinoid anandamide.4 Additionally, CBD has immunoregulatory effects that are of special interest in rheumatoid arthritis, which is characterized by immune cell infiltration into joints.3 For example, CBD can dose-dependently suppress lymphocyte proliferation.5 It also induces regulatory T-cells.3

It’s important to note that CBD does not inhibit either the COX-1 or COX-2 enzymes.6,7 Inhibition of these enzymes can lead to gastrointestinal ulcers and bleeding (COX-1) or myocardial infarctions and cerebrovascular events (COX-2).

Promising Preclinical Studies

A number of preclinical studies in rodent models have yielded promising results in regards to CBD’s ability to modulate joint health. Philpott and associates induced osteoarthritis (OA) in rats and then measured joint pain, inflammation, and joint nerve myelination.8 The researchers then observed the effects of both therapeutic and prophylactic peripheral CBD administration. In rats suffering from end-stage OA, CBD dose-dependently reduced joint afferent firing rate and improved weight bearing. CBD treatment also decreased acute,   transient joint inflammation. CBD administered prophylactically blocked the development of induced joint pain at later time points. Furthermore, CBD was neuroprotective. In summary, local CBD administration inhibited OA pain while prophylactic CBD treatment stopped the later development of pain and nerve damage in joints with OA.

In another rat model of arthritis, Hammell and colleagues induced arthritis in rats and then administered transdermal CBD for four consecutive days afterward.9 In a dose-dependent manner, transdermal CBD markedly improved joint swelling, spontaneous pain, immune cell infiltration, and thickening of the synovial membrane. The rats’ increased sensitivity to pain (hyperalgesia) was reduced after CBD administration. Additionally, levels of proinflammatory biomarkers declined after CBD.

Costa and coworkers determined the effect of oral administration of CBD.10 The researchers induced inflammation in rat paws. For three days after the onset of acute inflammation, the researchers administered 5-40 mg/kg of oral CBD to the animals. A single dose of CBD dose-dependently improved edema. Additional daily doses led to further reductions. Prostaglandin E2 plasma levels, generation of oxygen free radicals—all markers of inflammation—also declined after three doses of CBD.

A mouse model found similar results as the preceding rat studies. CBD administered either orally or through i.p. after the onset of clinical symptoms interfered with the progression of arthritis.5 CBD protected the joints against severe damage. There was also a decline in tumor necrosis factor release by knee synovial cells.

Conclusion

My personal clinical experience and the preclinical research that exists on CBD and joint health is intriguing. Given the results of the existing studies, it is somewhat surprising larger scale human studies investigating CBD and joint health have not been more actively pursued.  The promising results achieved with CBD in clinical practice indicates it is safe and effective. It should be noted, however, that the goal of CBD supplementation is balancing rather than overstimulating the endocannabinoid system. This is why I always have my patients start with a lower dosage of CBD and work up to a sufficient amount to produce optimal results.

References:

  1. Miller RJ, Miller RE. Is cannabis an effective treatment for joint pain? Clin Exp Rheumatol. 2017 Sep-Oct;35 Suppl 107(5):59-67.
  2. Hasenoehrl C, Taschler U, Storr M, Schicho R. The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease. Neurogastroenterol Motil. 2016;28(12):1765-80.
  3. Lowin T, Schneider M, Pongratz G. Joints for joints: cannabinoids in the treatment of rheumatoid arthritis. Curr Opin Rheumatol. 2019 May;31(3):271-8.
  4. Bisogno T, Hanus L, De Petrocellis L, et al. Molecular targets for cannabidiol and its synthetic analogues: effect on vanilloid VR1 receptors and on the cellular uptake and enzymatic hydrolysis of anandamide. Br J Pharmacol. 2001 Oct;134(4):845-52.
  5. Malfait AM, Gallily R, Sumariwalla PF, et al. The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis. Proc Natl Acad Sci U S A. 2000Aug 15;97(17):9561-6.
  6. Stott CG, Guy GW, Wright S. The effects of cannabis extracts Tetranabinex and Nabidiolex on human cyclooxygenase (COX) activity. Presented at the International Cannabinoid Research Society. June 2005 Clearwater, Florida.
  7. Burstein SH, Zurier RB. Cannabinoids, endocannabinoids, and related analogs in inflammation. AAPS J. 2009 Mar;11(1):109-19.
  8. Philpott HT, O’Brien M, McDougall JJ. Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis. Pain. 2017 Dec;158(12):2442-51.
  9. Hammell DC, Zhang LP, Ma F, et al. Transdermal cannabidiol reduces inflammation and pain-related behaviours in a rat model of arthritis. Eur J Pain. 2016 Jul;20(6):936-48.
  10. Costa B, Colleoni M, Conti S, et al. Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw. Naunyn Schmiedebergs Arch Pharmacol. 2004 Mar;369(3):294-9.