While the CUPID study failed to prove that cannabis slows multiple sclerosis progression, scientists are optimistic for the future of MS research.
In the first large-scale, multi-center
Dubbed CUPID (Cannabinoid Use in Progressive Inflammatory Brain Disease), the trial involved nearly 500 people with progressive MS. In progressive MS, there are no distinct relapses or remissions. Instead, patients experience a slow, steady decline with an accumulation of disability. It took eight years to complete the placebo-controlled study, which mapped patients’ disease progression over three years.
In the CUPID study, two-thirds of patients received dronabinol, a synthetic version of THC (the active chemical in cannabis), while the rest took a placebo. Patients took the medication daily for three years and their disability scores were mapped using the Expanded Disability Status Scale (EDSS). They also completed questionnaires rating the impact of MS on their daily lives.
CUPID failed to prove that dronabinol could slow MS progression, although some patients at the lower end of the disability scale did appear to benefit.
“The effect we found in people with less disability is very interesting, and needs further exploration. There are many possible explanations,” said John Zajicek, chief investigator of the CUPID study and a professor of clinical neuroscience at Plymouth University Peninsula Schools of Medicine and Dentistry. “The first is that this is a chance finding that won’t be repeatable,” he said. But he feels the most likely explanation is that “…these people are progressing the fastest, so we have most chance of seeing an effect.”
Taking the relaxing effects of cannabis into account, Zajicek told Healthline, “[It] may be that as people have more difficulty with walking, the anti-stiffness effect of cannabinoids means that we are removing the stiffness needed to remain walking, so we get a ‘masking’ of potential protective effects.”
Unpleasant side effects of dronabinol could also have played a role in the trial outcome. As Zajicek pointed out, “Side effects meant that people stopped medication more frequently in the active treatment arm.”
Sativex is currently the only licensed cannabis medication on the market, and some MS patients use it to treat symptoms like muscle cramping and pain.
CUPID researchers were surprised to find that, overall, MS progressed at a slower rate than they’d expected. This suggests that a longer trial might yield a more favorable result.
The problem is, according to Zajicek, that “MS studies in progressive disease are incredibly difficult to do. Three years is about as long as it is possible to keep people in trials.”
In the CUPID trial, patients didn’t deteriorate as fast as expected, so if researchers hope to see any potential effect of treatment, Zajicek said, “We need to make sure that in future we try and recruit people who have most chance of progressing.”
CUPID also aimed to improve the way MS clinical trials are conducted.
Zajicek said trials of progressive MS have always used the Expanded Disability Status Scale, “which is a very old measurement scale, with many shortcomings. In CUPID, we used patient-reported outcome as a co-primary measure, alongside the EDSS.”
And while traditional trials compare the study’s entire treatment group to the entire placebo group, Zajicek said, “This doesn’t take account of the vast amount of data every trial actually generates, and doesn’t allow us to estimate the size of benefit for any single person. By using newer methods, we should be able to spot sub-groups of people who may be most likely to benefit. Statistics has moved on considerably, but most clinical trials (in all diseases) don’t make the most of these advances.”
Zajicek emphasized, “There is a desperate need for more studies in progressive MS.” He added that the International Progressive MS Consortium is dedicated to organizing such research. “We need to extract as much information from the CUPID study as possible before we embark on more trials.”
An upcoming study called MS-SMART will use MRI scans to screen for a range of drugs that might help slow progressive MS. However, considering the financial and temporal burden of large-scale trials, Zajicek is hesitant to sign on for another round. “As [CUPID] took eight years, an incredible amount of effort, and overcoming major problems with funding, I’m not sure I’m the person to take this on,” he said.
And people with MS can have an impact. Let organizations like the National Multiple Sclerosis Society (NMSS) or the Multiple Sclerosis Association of America (MSAA) know there is a need. “If people affected by MS want me to take this forward,” said Zajicek, “and there are sufficient funds, then I might be persuaded.”
“We’re also trying to do studies in other areas of MS,” he added, “such as comparing some of the latest treatments head-to-head, and testing the value of adding vitamin D to see if this influences the disease course. There’s a lot that needs to be done.”