The trial’s purpose was to evaluate whether cannabis-based medicines have any psychological impact and/or any impact on cognitive performance, mood, pain and fatigue in participants undergoing treatment. The study started in February 2001.
Preliminary results from one year of this study were presented at the ECTRIMS 2003 conference. (18th Congress of the European Committee for Treatment and Research in Multiple Sclerosis). They showed that the cognitive scores of all the participants at the start and end of treatment within the study remained within the expected range for people with MS. Researchers have concluded that no significant effect on cognition was shown in people using medicinal cannabis. [3] Full results from the study are still awaited.
Lower urinary tract symptoms in MS
Anecdotal evidence suggests that cannabis might be beneficial for some bladder problems in MS. This randomised, controlled, double-blind study was designed as a subset of the main CAMS trial, to test the theory that cannabis-based medicine might improve urgency (the need to empty the bladder at very short notice) and increase day-to-day bladder capacity.All 657 participants in the CAMS trial were asked to complete diaries about whether they experienced urinary incontinence, and also quality of life questionnaires. 47 of these people also agreed to undergo tests for urodynamics - how the bladder works - and incontinence pad tests.
People taking either Cannador or dronabinol demonstrated an improvement of around 35% compared with placebo on the number of episodes of urge incontinence they experienced. However, there was no evidence of any treatment effect on any of the urodynamic measures, nor on quality of life. Still, these results do suggest that cannabis-based medicine may improve some bladder symptoms in MS. [4]
Tremor in MS
One very small randomised, double-blind, placebo-controlled crossover study looked at oral cannabis extract (Cannador) as a treatment for 14 people with MS who experienced tremor in their arms. No statistically significant difference was seen between cannabis-based medicine and placebo in terms of tremor, although people receiving cannabis-based medicine reported more relief than those who receiving placebo. [5]Swiss study of spasticity
57 people with MS undergoing inpatient rehabilitation participated in a randomised, double-blind crossover trial of oral cannabis-based medicine, over a three week period. Active drug was a whole-plant cannabis extract containing 2.5mg THC and 0.9mg CBD in a gelatine capsule. Participants received either active or placebo ingredients for two weeks in the main part of the study. The aim was to investigate whether this helped people who had poorly-controlled spasticity.Results showed no statistically significant differences were seen between cannabis-based medicine compared with placebo. However, minor improvements were seen for spasm frequency, mobility, and getting to sleep in people on cannabis-based medicine. More side-effects were seen in people receiving cannabis-based medicine rather than placebo, although these were manageable.
The researchers suggest cannabis-based medicine might be useful for people with MS whose spasticity is not responding to other drugs. [6]
Commercial cannabis-based medicine trials - Sativex trials
- Bladder dysfunction in advanced MS
- Multiple symptom relief
- Pain relief
- Spasticity
The majority of these trials were double-blind and used a placebo. Sativex was used as an additional treatment, rather than replacing any existing medicines.
Bladder dysfunction in advanced MS
An early Sativex trial was undertaken at the National Hospital for Neurology and Neurosurgery in London with a small number of people with MS with severe bladder problems. 21 people were recruited and results were reported from 15. Urinary urgency, the number of incontinence episodes and volume of urine lost, frequency of day-time and night-time urination all improved significantly following treatment. Participants’ own assessment of pain, spasticity and sleep also reported improvements.Multiple symptom relief
This trial involved 160 people from three centres across the UK. It looked at Sativex’s effect across five symptoms: spasticity, spasms, bladder problems, tremor and pain. Analysis of the results produced a negative result overall, as everyone in the trial reported an improvement on pain, despite whether they were receiving Sativex or placebo. When evaluation of the effect of pain was removed from the results, people who reported spasticity as their main symptom also showed statistically significant improvement on Sativex. Quality of sleep was also shown to improve significantly for people receiving Sativex. Slight but not statistically significant improvements were reached on a number of other measures.[8]Pain relief: A trial in Liverpool has found that Sativex is effective for people with MS experiencing dysaesthetic pain (uncomfortable, abnormal sensations, such as pins and needles, burning or crawling feelings, numbness or tightness) or painful spasms. 66 people received either cannabis-based medicine or placebo in a mouth spray. Pain and sleep disturbance were recorded daily on an 11-point rating scale. The treatment group reported an average reduction in the intensity of pain of 2.7 points as opposed to 1.4 in the placebo group. The effect on sleep disturbance was also marked, with a reduction of 2.5 points in the treatment group and 0.8 in the placebo group. Although the spray was well tolerated, some people reported dizziness, dry mouth, drowsiness and some effect on long-term memory.[9]
Spasticity: GW pharmaceuticals has recently reported the results of a new phase III trial, although these have yet to be formally published. The trial was a randomised placebo-controlled parallel group study in 335 people with spasticity due to MS. The duration of treatment in the study was 14 weeks.
Results showed that people on the trial who received Sativex, rather than placebo and who took the drug throughout the trial, experienced significant improvement in their spasticity. Unfortunately this difference was not repeated once results for everyone on the trial were analysed. These results include people who withdrew from the trial at any point. Overall this is a negative result although it suggests that Sativex can be a valuable treatment for some people with spasticity.
Separately, a pooled analysis across the three Sativex MS spasticity studies now completed, incorporating a total of 652 participants, shows Sativex to be superior to placebo .
CUPID (Cannabinoid Use in Progressive Inflammatory brain Disease)
Following on from CAMS, a new study, CUPID is due to start in 2006. This trial aims to recruit 500 people with progressive MS from around 25 hospitals across the UK.This is due to be a long-term study, and will look at whether delta-9 tetrahydrocannabinol (THC) can slow the increase of disability in people with progressive MS. Other outcome measures include whether THC provides symptomatic relief for spasticity. The trial will also try to assess the long-term safety of cannabis-based medicines. It is important to note that the cannabis-based medicine used in this trial will be different from that used in the CAMS or Sativex trials.Conclusion
The situation for cannabis-based medicine is in a state of flux. The current position, where Sativex is not licensed but is available to some people with MS, is unacceptable in the long-term. The MS Trust would like to see proper, unequivocal results from the research trials that clarify how far cannabis-based medicines are able to relieve MS symptoms. We also welcome any new research into the effects of cannabis on the brain, particularly in people with MS. Any work in this area is always welcome, to increase our understanding and offer hope to people whose MS is progressive.(published with permission in writing from:http://www.mstrust.org.uk)
