The main active constituent of cannabis - tetrahydrocannabinol or THC - has not shown to be effective in slowing the course of progressive multiple sclerosis (MS).

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 Medical Research Council Clinical Trials Unit and University College London and is the first large, non-commercial clinical study of THC for MS progression.

CUPID enrolled 498 people with MS from 27 centers around the UK and has taken eight years to complete. People with progressive MS were randomized 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).

The patients were randomly assigned to a treatment group, 329 received at least one dose of dronabinol and 164 received at least one dose of placebo (five did not receive the allocated intervention). 145 patients in the dronabinol group had EDSS score progression (0·24 first progression events per patient-year; crude rate) compared with 73 in the placebo group (0·23 first progression events per patient-year; crude rate).

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 enrollment 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."

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. 

Citation: 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, 'Effect of dronabinol on progression in progressive multiple sclerosis (CUPID): a randomised, placebo-controlled trial', The Lancet Neurology - 13 July 2013  DOI: 10.1016/S1474-4422(13)70159-5