MS Progression: Cannabis Active Ingredient Ineffective

Professor John Zajicek Professor of Clinical Neuroscience, Centre for Clinical Trials & Health Research - Translational & Stratified Medicine (Peninsula Schools of Medicine and Interview with:
Professor John Zajicek
Professor of Clinical Neuroscience, Centre for Clinical Trials & Health Research – Translational & Stratified Medicine (Peninsula Schools of Medicine and Dentistry) What are the main findings of the study?

Prof. Zajicek: Our study investigated whether dronabinol (one of the major active ingredients of cannabis) may slow the progression of multiple sclerosis. We currently have no treatments that are effective in modifying the disease course in people with either primary or secondary MS. We did a clinical trial across the UK involving nearly 500 patients, who were randomly allocated to dronabinol or placebo, and followed them up for three years to look at progression on rates. Overall we failed to find an effect of dronabinol on disease progression,  either clinically (using a variety of clinical measures) or using magnetic resonance imaging (MRI). There was a suggestion of an effect in people with the least disability (who didn’t need a stick to help them walk), and there were no major problems with serious side effects.  However, over all the population that took part in the study also progressed less than we expected, which reduced our chances of finding an effect of treatment. The  study was not designed to investigate an effect on MS-related symptoms (such as pain and muscle stiffness), which have been investigated before.  Where any of the findings unexpected?

Prof. Zajicek: It was disappointing that we did not get an overall effect, but encouraging  that there may be an effect in people with less disability. One of the surprising findings was the relative lack of progression in the overall group  of patients who took part. Side effects of active treatment also meant that  people stopped taking active treatment, also reducing the chance of a positive result. We will use this study to plan future studies to ensure we can design trials that are most likely to have a chance of finding an effect i f one is present.  What should patients and providers take away from this study?

Prof. Zajicek: This is essentially another negative study looking for treatment in a neurodegenerative disorder. We desperately need treatments not only for progressive MS, but also Parkinson’s and Alzheimer‘s diseases. Our results do not detract from the established symptomatic benefit that has been identified in previous  shorter-term studies of cannabinoids.  What further research do you recommend as a result of your report?

Prof. Zajicek: The relative absence of treatments for neurological degeneration, means that we should take every opportunity to follow each lead, however slender. Future studies in MS should focus on people most likely to progress over the course of a trial, and further studies of cannabinoid treatments should occur, using lower doses to encourage greater retention on treatment.


Effect of dronabinol on progression in progressive multiple sclerosis (CUPID): a randomised, placebo-controlled trial

Prof John Zajicek PhD,Susan Ball MSc,Prof David Wright PhD,Jane Vickery MSc,Prof Andrew Nunn MSc,Prof David Miller FMedSci,Mayam Gomez Cano PhD,David McManus MSc,Sharukh Mallik MSc,Prof Jeremy Hobart PhD,on behalf of the CUPID investigator group
The Lancet Neurology – 13 July 2013
DOI: 10.1016/S1474-4422(13)70159-5

Press Release: July 22 2013

Cannabis constituent has no effect on MS progression, study shows

But there may be some benefit to those at the lower end of the disability scale

The first large non-commercial clinical study to investigate whether the main active constituent of cannabis (tetrahydrocannabinol or THC) is effective in slowing the course of progressive multiple sclerosis (MS), shows that there is no evidence to suggest this; although benefits were noted for those at the lower end of the disability scale.

The study is published in The Lancet Neurology.

The CUPID (Cannabinoid Use in Progressive Inflammatory brain Disease) study was carried out by researchers from Plymouth University Peninsula Schools of Medicine and Dentistry. The study was funded by the Medical Research Council (MRC), the Multiple Sclerosis Society and the Multiple Sclerosis Trust, and managed by the National Institute for Health Research (NIHR) on behalf of the MRC-NIHR partnership.

CUPID enrolled nearly 500 people with MS from 27 centres around the UK, and has taken eight years to complete. People with progressive MS were randomised to receive either THC capsules or identical placebo capsules for three years, and were carefully followed to see how their MS changed over this period. The two main outcomes of the trial were a disability scale administered by neurologists (the Expanded Disability Status Scale), and a patient report scale of the impact of MS on people with the condition (the Multiple Sclerosis Impact Scale 29).

Overall the study found no evidence to support an effect of THC on MS progression in either of the main outcomes. However, there was some evidence to suggest a beneficial effect in participants who were at the lower end of the disability scale at the time of enrolment but, as the benefit was only found in a small group of people rather than the whole population, further studies will be needed to assess the robustness of this finding.

One of the other findings of the trial was that MS in the study population as a whole progressed slowly, more slowly than expected. This makes it more challenging to find a treatment effect when the aim of the treatment is to slow progression.

As well as evaluating the potential neuroprotective effects and safety of THC over the long-term, one of the aims of the CUPID study was to improve the way that clinical trial research is done, by exploring newer methods of measuring MS and using the latest statistical methods to make the most of every piece of information collected. This analysis continued for several months and has provided important information about conducting further large scale clinical trials in MS.

Professor John Zajicek, Professor of Clinical Neuroscience at Plymouth University Peninsula Schools of Medicine and Dentistry, said: “To put this study into context: current treatments for MS are limited, either being targeted at the immune system in the early stages of the disease or aimed at easing specific symptoms such as muscle spasms, fatigue or bladder problems. At present there is no treatment available to slow MS when it becomes progressive. Progression of MS is thought to be due to death of nerve cells, and researchers around the world are desperately searching for treatments that may be ‘neuroprotective’. Laboratory experiments have suggested that certain cannabis derivatives may be neuroprotective.”

He added: “Overall our research has not supported laboratory based findings and shown that, although there is a suggestion of benefit to those at the lower end of the disability scale when they joined CUPID, there is little evidence to suggest that THC has a long term impact on the slowing of progressive MS.”

Last Updated on September 19, 2013 by Marie Benz MD FAAD