Research: Cannabis and Spasticity. I didn't Inhale..Maybe you Should?

Corey-Bloom J et al. Smoked cannabis for spasticity in multiple sclerosis: a randomized, placebo-controlled trial CMAJ cmaj.110837; published ahead of print May 14, 2012, doi: 10.1503/cmaj.110837

Background: Spasticity is a common and poorly controlled symptom of multiple sclerosis. Our objective was to determine the short-term effect of smoked cannabis on this symptom.
 
Methods: We conducted a placebo-controlled,crossover trial involving adult patients with multiple sclerosis and spasticity. We re -cruited participants from a regional clinic or by referral from specialists. We randomly assigned participants to either the intervention (smoked cannabis, once daily for three days) or control (identical placebo cigarettes, once daily for three days). Each participant was assessed daily before and after treatment. After a washout interval of 11 days, participants crossed over to the opposite group. Our primary outcome was change in spasticity as measured by patient score on the modified Ashworth scale. Our secondary outcomes included patients’ perception of pain (as measured using a visual analogue scale), a timed walk and changes in cognitive function (as measured by patient performance on the Paced Auditory Serial Addition Test), in addition to ratings of fatigue.

Results: Thirty-seven participants were randomized at the start of the study, 30 of whom completed the trial. Treatment with smoked cannabis resulted in a reduction in patient scores on the modified Ashworth scale by an average of 2.74 points more than placebo (p < 0.0001). In addition, treatment reduced pain scores on a visual analogue scale by an average of 5.28 points more than placebo (p =
0.008). Scores for the timed walk did not differ significantly between treatment and placebo (p = 0.2). Scores on the Paced Auditory Serial Addition Test decreased by 8.67 points more with treatment than with placebo (p = 0.003). No serious adverse events occurred during the trial. 

Interpretation: Smoked cannabis was superior to placebo in symptom and pain reduction in participants with treatment-resistant spasticity. Future studies should examine whether different doses can result in similar beneficial effects with less cognitive impact.

Many years ago (2000) we produced the first objective evidence for the cannabinoid control of spasticity (limb stiffness) in experimental systems. In 2010 Sativex a sublingual (under the tongue) spray was approved for the treatment of spasticity in the UK. The major trials have consistently reported percieved benefit from the MSers but cannabis has faired less well on clinically assessed measures of spasticity notable the Ashworth Score. This is a scale rated by the clincial or physiotherapist as follows:

 1.No increase in muscle tone.
2. Slight increase in tone giving a “catch” when affected part is moved in flexion or extension.
3. More marked increase in tone but affected part is easily flexed.
4. Considerable increase in tone; passive movement difficult.
5. Affected part is rigid in flexion or extension.

This scale is very insensitive to change and many agents used to treat spasticity, did not show an effect on the Ashworth scale. In trials of Sativex hundreds of people have been enrolled and there has not been reports of a change in the Ashworth Scale (A clinician-based measure of spasticity). It looks like some people can response to drug and some do not. There has also been a trial on oral cannador (a cannabis extraxct) in a trial involving six hundred people and did not show an intial effect on the Ashworth Scale in a trial lasting about 6 weeks comparing drug to placebo groups. 

In a before and after study of mice treated with cannabis, we could show an effect within ten-thirty minutes in less than 10 animals. 

Those animal studies told us: 
(a) Cannnabis works because is acting on a biological system that is attempting to control spasticity, 
(b) The main ingredient in cannabis for symptom relief is because of tetrahydrocannabinol in cannabis and the cannabinoid one(CB1) receptor in the nervous system. 
(c) If you are aiming to take a dose that does not cause the euphoria associated with cannabis use, then if you do not know you are getting cannabis, you are not getting enough! This is because the CB1 receptor is controlling both the symptomatic effect and the cannabinoid psychoactivity (being stoned) is caused by the same receptor but located in different bits of the brain and you can't hit one without the other occuring.

(d) The oral route is the one where you have least control on dosing because (a) The drug is slowly absorbed and gets bound in dietry and body fat. The drug does through the liver (first pass metabolism) and most of the drug gets broken down before it gets to go to the heart, round the lungs, back to the heart and then off to the brain. The drug arrives slowly and lasts along time at modest levels. The sublingual route means the drug gets aborbed in the blood vessels in the mouth before going to  the heart, round the lungs back to heart and off to the brain. Some gets swallowed. Smoke cannabis goes from lungs to the heart to the brain and you get a rapid peak, so the smoked route was always going to be the most-informative. However, the medical fraternity has been raising battle against smoking and the risk of lung cancer etc, etc, and so is a retrograde step to deliver a medicine by smoke.


However, this study examined spasticity before and after smoked cannabis  and the same people were tested with a placebo and there was a significant reduction in the Ashworth Scale on 30 patients treated for only 3 days. This showed an effect although as anticipated the people were "stoned". If this study had been done years ago, when it should have saved alot of time with the regulators and convincing the medical fraternity of the value of the cannaboind system for the control of spasticity and pain. In addition there would have been more effort is developing a non smoked alternative for cannabinoid delivery, such as as an inhaler. Although it can be argued that heating of the cannabis can have chemical benefits. The study was unblinded in relation what people were taking and the people undertaking the study were cannabis aware, which would aid to the unblinding effect. 

Read the study it is open acccess
 The question is where next? Surely this needs repeating but the question is whether smoked cannabis should become legalised for medical use?  As mentioned already this would be seen as a retograde step.  The problem with a smoked medical cannabis is that creates a portal for the legalise cannabis campaign, with a subtext of recreactional use. I think it is best to keep the recreational and medicinal cannabinoids as seperate issues. We can now do this experiementally Some people use medical marijuana as a means to get recreational drugs "medication". I am sure the"high" is part of the beneficial effect for some people.
 N.B. Cannabis possession in the UK is currently illegal

Now what we want next is evidence that cannabis can have an effect on progressive MS. The biology is there, the experimental evidence is there and the first trial (CUPID) of an (Oral) cannabinoid for the treatment of progressive MS is completed. Anouncment imminent...fingers crossed.

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