Could cannabis compound soothe arthritis pain?

Tuesday January 7 2014

“Synthetic cannabis-like molecule developed in lab could help osteoarthritis sufferers,” reports The Daily Telegraph.

Anecdotal reports of cannabis’s ability to soothe chronic pain conditions such as osteoarthritis have been available for many years.

Aside from the obvious legal issues (cannabis is a Class B illegal drug), cannabis also carries the risk of side effects and complications such as psychosis and depression.

So a compound containing the drug’s painkilling ability without its psychoactive effects could lead to useful new treatments. 

One candidate is “JWH133” a chemical that binds to and activates the cannabinoid 2 (CB2) receptor. Receptors are proteins found on the surfaces of cells. When activated receptors cause a response inside cells. The CB2 receptor is also activated by tetrahydrocannabinol (THC), the principal psychoactive constituent in cannabis. Activating the CB2 receptor is thought to relieve pain and inflammation. 

The new research found evidence that JWH133 relieves pain in a rat model of arthritis. Importantly, the JWH133 compound is selective for CB2 receptors and does not activate cannabinoid 1 (CB1) receptors. CB1 receptors are found in the brain and are believed to be responsible for the psychological effects of cannabis.

So this suggests JWH133 may be a useful candidate for an osteoarthritis treatment. However, this is very early stage research only involving rats.

As Professor Alan Silman, medical director of Arthritis UK, says in the press coverage, this research does not support recreational cannabis use.

Where did the story come from?

The study was carried out by researchers from the University of Nottingham in the UK in collaboration with researchers from the University of Pittsburgh and Virginia Commonwealth University in the US. It was funded by Arthritis Research UK and the National Institutes of Health.

The study was published in the peer-reviewed journal PLOS One. PLOS One is an open-access journal, meaning that all the research it publishes can be accessed for free.

This study was reported on by the Daily Express and The Telegraph. The Telegraph made no mention of the fact that the current research was in rats. This was also unclear from the over-optimistic headline in the Express. However, the report in the Express was of a higher standard, as it explained that the research was in animals and that it would take a considerable amount of time before any pill could be available for patients.

What kind of research was this?

This was a laboratory experiment on animals.

The researchers wanted to test the hypothesis that activation of cannabinoid 2 (CB2) receptors would reduce osteoarthritis pain responses in an animal model of osteoarthritis.

What did the research involve?

To create the animal model of osteoarthritis, rats had an injection of a chemical (monosodium acetate) into one of their knees (on the left rear limb). This triggered the same kind of inflammation and functional damage to the limb that occurs in humans with osteoarthritis.

The rats were then either given a drug called JWH133 or a placebo (“dummy”) injection. JWH133 binds with and activates the CB2 receptor of cells, causing them to respond. Eight rats were injected with JWH133 and eight were injected with placebo.

Pain behaviour was determined by measuring the change in weight distribution between the limbs and by testing the rats' sensitivity to pinch and touch.

Further experiments were performed on the animal model of osteoarthritis and normal rats that had been given an injection of saline (salty water) into their knee to see how JWH133 could reduce pain.

What were the basic results?

Once the rats had the injection of monosodium acetate into the knee of their left rear limb to model osteoarthritis, they placed less weight on that limb and their paw was more sensitive to pinch and touch.

Repeated injections with JWH133 significantly reduced the development of pain behaviour in the osteoarthritis model rats compared to the placebo injection.

The researchers went on to perform a series of further experiments. They found that:

  • treatment with JWH133 reduced the changes in inflammation-controlling chemicals which are released by osteoarthritis model rats
  • treatment with JWH133 reduced the firing of nerve cells in the spine in response to pain in osteoarthritis model rats, but not normal rats
  • osteoarthritis model rats have higher levels of the CB2 receptor “message” (mRNA) and protein in nerve cells in the spine

The researchers then looked at the levels of CB2 receptor “message” in human spines of people who had died who had had knee osteoarthritis. They found that the more severe the disease, the lower the level of CB2 receptor “message”. The researchers say that this might reflect “events associated with later stages of joint pathology [disease]”.

How did the researchers interpret the results?

The researchers conclude that “activation of CB2 receptors attenuated [reduced] the development and maintenance of osteoarthritis-induced pain behaviour”. They go on to state that their “clinical and pre-clinical data support the further investigation of the potential of CB2 receptor agonists [chemicals that bind to the receptor and activate it] for the treatment of pain associated with osteoarthritis, in particular at earlier stages of the disease”.

Conclusion

This study found that a chemical called JWH133, which binds to and activates the cannabinoid 2 (CB2) receptor, could reduce osteoarthritis-induced pain behaviour in rats injected with a chemical to mimic the effects of osteoarthritis.

This early stage research supports the further investigation of the potential of chemicals which bind to activate the CB2 receptor as treatments for osteoarthritis-induced pain. However, so far the treatment has only been tested in a small number of rats injected with a chemical to mimic symptoms of osteoarthritis. This study does not show what positive or negative effect chemicals that activate the CB2 receptor may have in humans suffering from osteoarthritis.

Until further trials involving humans, such as a phase I trial are carried out, it is impossible to predict whether JWH133 will be effective, and probably more importantly, safe in humans.

If you are having problems coping with your arthritis symptoms, the NHS offers specialist services for people with chronic pain conditions.

Read more about NHS Services for people with chronic pain.

Analysis by Bazian
Edited by NHS Choices