In the original large trials of cannabis in MS, there was a failure to see any changes in the Ashworth Scale. This also happened in trials with baclofen and tizanidine too. This indicates that it is insensitive to small changes. However, the people in the trials felt that their spasticity was improving. Eventually the companies convinced the regulators to accept visual analogue scales where the people taking the drug rated the effect rather than the physician-rated Ashworth Scale.
We have invented a scale to look at spasticity in rodents should we call it the Mashworth..mouse Ashworth? :-)
One other way is to get physical measures of change and this could be via electrophysiology. You can stimulate a nerve and the electric signal from an electrode stimulator can stimulate the nerve to send a signal directly to the muscle, which can be measured. This is called the M wave. However, the electrode signal can travel the other way up the nerve into the spinal cord. The signal travels from the nerve and makes a synapses with the motor nerve that sends the signal down to the muscle and this is gives an electrical signal a few thousandth of a second later and this is called the H wave. In the mouse if you stimulate the sciatic nerve in the leg it takes about 2 milli seconds to make the M wave and an extra 7 milli-seconds to make the H wave. Its a bit like an echo of the M wave and in healthy people an animals the H wave is quite small. But when you have spasticity the inhibitory signals normally present in the spinal cord are reduced and so the H wave is exaggerated and is a measure of spasticity.
In this study whilst surprisingly they could see an effect on the Ashworth Scale, when they looked they did not see any influence on the M/H ratio (if the drug had an effect on spasticity the H wave should have been reduced). This shows that this electrophysiology outcome is not always responsive to drug treatment. In a previous study they did not find any influence either.
Centonze D, Mori F, Koch G, Buttari F, Codecà C, Rossi S, Cencioni MT, Bari M, Fiore S, Bernardi G, Battistini L, Maccarrone M.Lack of effect of cannabis-based treatment on clinical and laboratory measures in multiple sclerosis. Neurol Sci. 2009;30(6):531-4.
For this reason we are not concentrating on electrophysiology in our ongoing clinical trial with an new anti-spastic tiral
Canbex - Phase II proof of concept trial VSN16R
Investigators: R Farrell (CI) UCLH, Dr Clarence Liu (Barts Health),
4 phases:
Screening and wash out
Daily single escalating dose – 5 days
Three weeks twice daily stable dosing
Washout and end of study review
Eligibility:
Be between 18 and 70 years of age
Have MS
Able to walk 20 metres ( with aid as needed)
Have spasticity
Not on medication or willing to withdraw current medication
Please note you cannot self-refer for clinical trials you have to be referred via your neurologist, clinical nurse specialist or general practitioner.
CoI I am founder, shareholder consultant to Canbex, which will compete with sativex.