Largest MS Cannabinoid Trial Found Small But Significant Spasticity Benefit After 12 Months | Research

The takeaway

The 12-month follow-up of 630 MS patients from the CAMS study found THC produced a small but statistically significant reduction in spasticity on the Ashworth scale (P = 0.01 adjusted), suggesting a longer-term treatment effect beyond what the initial 15-week study showed.

Read this if you have MS spasticity and want to know about the longest-running randomized trial of cannabinoids for this condition.

THC showed significant spasticity reduction at 12 months (P = 0.01) after the initial 15-week study was negative

What the researchers found

This was the 12-month follow-up to the main Cannabinoids in Multiple Sclerosis (CAMS) study, the largest RCT of cannabinoids for MS at the time. Six hundred thirty patients from 33 UK centers had been randomized to oral THC, cannabis extract, or placebo in the initial 15-week study, which had not found significant Ashworth score changes.

Eighty percent of patients continued into this blinded follow-up. At 12 months, intention-to-treat analysis revealed a small but significant treatment effect for THC on the Ashworth spasticity scale (mean reduction 1.82 for THC vs. -0.23 for placebo, P = 0.01 adjusted for ambulatory status and center). Cannabis extract showed a smaller, non-significant effect.

There were suggestive findings for THC benefits on some aspects of disability. No major safety concerns emerged over the 12-month period. Patients generally reported feeling the drugs were helpful.

Why it matters

The finding that THC produced a significant spasticity benefit at 12 months, when the initial 15-week study had not, suggests that cannabinoid effects on spasticity may take time to develop or that the Ashworth scale may be insensitive to early changes. This result was important for the broader case that cannabinoids have a role in MS management.

The numbers in context

630 patients from 33 UK centers. 80% followed for 12 months. THC Ashworth reduction: 1.82 (n=154). Cannabis extract: 0.10 (n=172). Placebo: -0.23 (n=176). P = 0.01 adjusted. No major safety concerns.

How the study worked

Double-blind follow-up study extending the original 15-week CAMS trial. Six hundred thirty MS patients from 33 UK centers originally randomized to oral THC, cannabis extract, or placebo. Eighty percent followed for 12 months. Primary outcome: change in Ashworth spasticity scale. Secondary outcomes: Rivermead Mobility Index, timed walk, disability scores, quality of life.

What this study cannot tell us

The treatment effect, while statistically significant, was small. Cannabis extract did not show a significant effect, complicating interpretation. Eighty percent follow-up means 20% were lost, potentially biasing results. The Ashworth scale has known limitations as a measure of spasticity.

How to read the evidence

Large, multi-center, double-blind RCT with 12-month follow-up. Strongest evidence level, though the treatment effect was small and cannabis extract was not significant.

When this study was published

Published in 2005. The CAMS study remains one of the most cited cannabinoid-MS trials and contributed to subsequent regulatory approvals.

The bigger picture

The CAMS study and its follow-up remain among the largest and most rigorous RCTs of cannabinoids for MS. The delayed treatment effect raises important questions about how and when to assess cannabinoid efficacy. The results contributed to the eventual approval of cannabis-based medicines for MS spasticity.

Questions still open

Why did THC but not cannabis extract show a significant effect? Does the delayed onset of benefit reflect disease modification rather than just symptom relief? How does the clinical significance of the spasticity improvement translate to patients' daily functioning?

Common questions

Did cannabinoids help with MS spasticity in this trial?

THC produced a small but statistically significant reduction in spasticity at 12 months (P = 0.01), though the initial 15-week study had been negative. Cannabis extract did not show a significant effect. The delayed benefit suggests cannabinoid effects on spasticity may take time to develop.

Was this trial large enough to be reliable?

With 630 patients from 33 centers and 80% completing 12 months, this was one of the largest and most rigorous cannabinoid trials ever conducted. The small effect size was statistically significant but the clinical meaningfulness has been debated.

Read the original research

Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up.

Journal of neurology, neurosurgery, and psychiatry, 76(12), 1664-9

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Citation

Zajicek, J P; Sanders, H P; Wright, D E; Vickery, P J; Ingram, W M; Reilly, S M; Nunn, A J; Teare, L J; Fox, P J; Thompson, A J. (2005). Cannabinoids in multiple sclerosis (CAMS) study: safety and efficacy data for 12 months follow up.. Journal of neurology, neurosurgery, and psychiatry, 76(12), 1664-9.