Abstract

Cannabinoids have been shown to reduce MS-related symptoms, as well as potentially having a longer-term beneficial effect. This potential disease modifying effect is supported by in vitro evidence for neuroprotection. This led to the development of the current CUPID trial, a 30 centre, 493 patient parallel group randomised, placebo controlled trial over a 3-year treatment period. Patients with primary or secondary progressive MS, deemed to be deteriorating by their treating neurologists, with an Expanded Disability Status Score (EDSS) of between 4.0 and 6.5, were allocated to either oral Δ9 tetrahydrocannabinol, or placebo in a 2:1 ratio over the period May 2006–July 2008. An initial dose titration phase was used to optimise dosage whilst minimising side effects. Patients were followed up at 6 monthly intervals for 3 years before coming off medication. Primary outcome measures were reduction in time to EDSS progression maintained for at least 6 months (physician measure), and overall mean change from baseline to the end of the study in the MSIS-20 V.2 (patient-orientated measure). Secondary outcome measures included the Multiple Sclerosis Functional Composite, MSWS-12, symptom measures, SF-36, MSSS-88, and MRI outcomes in just over half of all patients. The study was powered to allow for 15% loss to follow-up, which was the eventual drop-out figure. This is the only non-commercial large multicentre controlled trial to have been conducted for progressive MS in the UK, and results will be presented.