Cannabis-Based Mouth Spray Reduced Spasticity in People With Multiple Sclerosis | Research

The takeaway

A THC/CBD mouth spray was significantly more effective than placebo at reducing MS-related spasticity, with 40% of treated patients achieving meaningful relief.

Read this if you have MS-related spasticity or want to understand the clinical evidence behind Sativex.

40% of patients achieved 30%+ spasticity improvement with the THC/CBD spray

What the researchers found

In this double-blind trial, 189 people with multiple sclerosis and spasticity were randomized to receive either a cannabis-based mouth spray containing THC and CBD (n=124) or placebo (n=65) for six weeks.

The primary analysis showed the active preparation was significantly superior to placebo (p=0.048) in reducing daily spasticity scores recorded by patients. All secondary measures, including the Ashworth spasticity scale and subjective spasm assessment, favored the active treatment, though they did not reach statistical significance individually.

In a responder analysis, 40% of patients on the active treatment achieved at least 30% improvement, a rate significantly higher than placebo (p=0.014). Six patients on the active spray and two on placebo withdrew due to adverse events.

Why it matters

MS spasticity is often difficult to manage with existing medications. This trial provided evidence that a standardized cannabis-based medicine could offer meaningful relief for a significant proportion of patients, contributing to the eventual approval of nabiximols (Sativex) in multiple countries.

The numbers in context

189 patients randomized (124 active, 65 placebo). Primary outcome: p=0.048 favoring active treatment. 40% of active group achieved 30% or greater improvement (p=0.014). 8 withdrawals due to adverse events (6 active, 2 placebo).

How the study worked

This was a randomized, double-blind, placebo-controlled trial. 189 MS patients with spasticity received daily doses of either a standardized oromucosal (mouth spray) cannabis-based medicine containing THC and CBD, or placebo, for 6 weeks. The primary endpoint was change in a daily patient-recorded numerical rating scale of spasticity.

What this study cannot tell us

The 6-week duration may not capture long-term efficacy or safety. The 2:1 randomization ratio gave less statistical power to detect differences. Secondary endpoints did not reach significance, and the primary endpoint p-value was close to the threshold.

How to read the evidence

This is a well-designed randomized, double-blind, placebo-controlled trial with adequate sample size, providing strong evidence for efficacy in MS spasticity.

When this study was published

Published in 2007. Nabiximols (Sativex) has since been approved in over 25 countries for MS spasticity based on this and subsequent trials.

The bigger picture

This study was part of the clinical development program for nabiximols (Sativex), which has since been approved in numerous countries for MS spasticity. It helped establish that a standardized cannabis formulation could meet the rigorous standards of pharmaceutical clinical trials.

Questions still open

Does the benefit persist beyond 6 weeks? Which MS patients are most likely to respond? Could higher doses improve the response rate without unacceptable side effects?

Common questions

What is the cannabis-based medicine used in this study?

It was a standardized oromucosal spray containing both THC and CBD extracted from the cannabis plant, later marketed as Sativex (nabiximols). It is sprayed under the tongue or inside the cheek.

Did all patients improve?

No. While the group average favored the treatment, 40% of patients achieved meaningful improvement (30% or more), meaning the majority had smaller or no measurable benefit.

Read the original research

Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis.

European journal of neurology, 14(3), 290-6

View on PubMed ↗

Citation

Collin, C; Davies, P; Mutiboko, I K; Ratcliffe, S. (2007). Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis.. European journal of neurology, 14(3), 290-6.