Protection from osteoarthritis may lie in our own joints

May 18, 2014

Science Daily/European Calcified Tissue Society

A recent study conducted by researchers at the University of Edinburgh is suggesting a strong link between osteoarthritis, which causes pain and stiffness in the joints and is the most common form of arthritis, and the endocannabioid system, which is found in the synovial tissue and fluid that surround joints. The endocannabinoid system is composed of cannabinoid receptors (which are more popularly known for managing the body's response to the psychoactive effects of cannabis) and endocannabinoid ligands. The type 2 cannabinoid receptor (CB2), is proving to be a significant source of defence against this potentially debilitating disease, which can affect all ages and is particularly common among the elderly.

The findings, which offer the eventual promise of new forms of protection, were presented at the 41st European Calcified Tissue Society Congress, held in Prague on May 17 -- 20, 2014, by Professor Stuart Ralston, Arthritis Research UK Professor of Rheumatology at the University of Edinburgh. Prof Ralston described how a study of mice with destabilised knee joints showed that cartilage degeneration, which lies at the heart of osteoarthritis, was up to 40% more severe in mice who were deficient in CB2 receptors, when compared to 'normal' mice, with the figure reaching up to 60% more severe among aged mice that developed spontaneous osteoarthritis and were deficient in CB2 receptors, when compared to their aged 'normal' counterparts.

The study also showed that a synthesised cannabinoid ligand, HU308, significantly inhibited the progression of arthritis in younger mice with normal levels of CB2 and had no effect on those with CB2 receptor deficiency.

Professor Ralston said: "Learning what provides natural protection against osteoarthritis can potentially give us a much greater insight into how we can develop treatments. We know from this study that, in mice, a CB2 receptor deficiency means a much higher likelihood of developing osteoarthritis and that the use of the synthesised cannabinoid, HU308, in normal mice offers additional protection against the disease.

"Our next step, we hope, is to investigate the role of the CB2 pathway in humans with osteoarthritis."

https://www.sciencedaily.com/releases/2014/05/140518092722.htm

Drugs related to cannabis have pain-relieving potential for osteoarthritis

January 7, 2014

Science Daily/University of Nottingham

Chemical compounds synthesized in the laboratory, similar to those found in cannabis, could be developed as potential drugs to reduce the pain of osteoarthritis.

These compounds could also reduce joint inflammation, according to new research carried out at the Arthritis Research UK Pain Centre at The University of Nottingham.

Cannabis contains a number of natural chemicals called cannabinoids and the brain has the ability to respond to such compounds. Cannabis and synthetically manufactured cannabinoid compounds can relieve pain in animal models of arthritis, but their use has been limited because of undesirable psychological side-effects.

Now a team of researchers led by Professor Victoria Chapman at the Arthritis Research UK Pain Centre at The University of Nottingham have shown that selectively targeting one of the molecules involved in the body's natural pain-sensing pathways, called cannabinoid receptor2 (CB2) can also reduce pain in animal models of osteoarthritis. This works in part through the central nervous system (spinal cord and brain). The compound used in this study, called JWH133, is a synthetic cannabinoid molecule manufactured in a laboratory and is not derived from the cannabis plant.

When the research was extended to humans, studies of the human spinal cord tissue showed for the first time the presence of this receptor and, interestingly, that the amount of receptor was related to the severity of the osteoarthritis. This provides evidence from patients that this drug target may have clinical relevance to osteoarthritis pain.

Cannabinoids are known to have anti-inflammatory effects, and the team have demonstrated that JWH133 reduced the levels of inflammation in their studies of osteoarthritis. Thus, cannabinoid CB2 targeted drugs may have a dual beneficial effect for people with osteoarthritis by providing pain relief as well as reducing inflammation in the joint.

Their findings are published online in the journal PLOS One.

Victoria Chapman, Professor of Neuropharmacology, said: "This finding is significant, as spinal and brain pain signalling pathways are known to make a major contribution to pain associated with osteoarthritis. These new data support the further evaluation of the selective cannabinoid-based interventions for the treatment of osteoarthritis pain."

Professor Alan Silman, medical director of Arthritis Research UK, added: "Millions of people are living with the severe, debilitating pain caused by osteoarthritis, and better pain relief is urgently needed. This research does not support the use of recreational cannabis use. What it does suggest is that there is potential to develop a synthetic drug that mimics the behavior of cannabinoid receptors without causing serious side effects."

Osteoarthritis affects eight million people the UK and occurs when the cartilage at the ends of bones wears away, causing joint pain and stiffness, and is a major cause of pain and disability. Current treatment is limited to pain relief, exercise, physiotherapy weight-loss and joint replacement. There are currently no drugs that slow down its progression, and more effective treatment is urgently needed.

https://www.sciencedaily.com/releases/2014/01/140107092825.htm