Sativex Spray Significantly Reduced MS Spasticity But Not Other Symptoms in 160-Patient Trial | Research

The takeaway

In a randomized trial of 160 MS patients using Sativex oromucosal spray, spasticity scores improved significantly compared to placebo (P = 0.001), but the primary outcome measuring each patient's most troublesome symptom did not reach significance.

Read this if you have MS-related spasticity and want to know about clinical trial evidence for cannabis-based sprays.

Spasticity VAS scores significantly reduced by Sativex vs. placebo (P = 0.001)

What the researchers found

Researchers recruited 160 MS outpatients experiencing significant problems with spasticity, spasms, bladder issues, tremor, or pain across three centers. Patients received either matched placebo or whole-plant cannabis extract (Sativex) containing equal amounts of THC and CBD at doses of 2.5 to 120 mg each daily via oromucosal spray.

The primary outcome, a visual analogue scale (VAS) score for each patient's most troublesome symptom, improved in both groups but did not reach statistical significance between them.

However, spasticity VAS scores were significantly reduced by Sativex compared to placebo (P = 0.001). There were no significant adverse effects on cognition or mood, and intoxication was generally mild.

Why it matters

While the primary outcome was negative, the significant improvement in spasticity specifically (P = 0.001) suggested that Sativex may be effective for this particular MS symptom. This trial contributed to the evidence base that eventually led to Sativex receiving regulatory approval for MS spasticity in multiple countries.

The numbers in context

160 MS patients across three centers. Sativex dose range: 2.5-120 mg THC and CBD daily. Primary symptom VAS: not significant between groups. Spasticity VAS: significantly reduced (P = 0.001). No significant cognitive or mood adverse effects.

How the study worked

Parallel group, double-blind, randomized, placebo-controlled study across three centers. One hundred sixty MS outpatients experiencing problems with spasticity, spasms, bladder issues, tremor, or pain received oromucosal spray of placebo or Sativex (equal THC and CBD, 2.5-120 mg daily). Primary outcome was VAS score for each patient's most troublesome symptom. Secondary outcomes included VAS scores for other symptoms, disability, cognition, mood, sleep, and fatigue.

What this study cannot tell us

The primary endpoint did not reach significance. The wide dose range (2.5-120 mg) means individual dosing varied substantially. The study grouped patients with different primary symptoms together, which may have diluted the overall treatment effect.

How to read the evidence

Multi-center randomized controlled trial with adequate sample size, though the primary endpoint was negative. The significant spasticity finding was a secondary outcome.

When this study was published

Published in 2004. Sativex has since been approved for MS spasticity in over 25 countries based on this and subsequent trials.

The bigger picture

This trial is part of a series of studies that built the case for Sativex as a treatment for MS spasticity. The pattern of significant improvement in spasticity specifically, but not across all MS symptoms, helped refine the therapeutic target for cannabis-based medicines in MS treatment.

Questions still open

Would a trial focused exclusively on MS spasticity patients show stronger overall results? What is the optimal dose range for spasticity specifically?

Common questions

Did Sativex help with all MS symptoms?

No. The primary outcome measuring each patient's most troublesome symptom was not significantly better than placebo. However, spasticity specifically showed significant improvement (P = 0.001). Other symptoms like pain, tremor, and bladder problems did not show significant benefits.

Did Sativex cause cognitive problems?

No significant adverse effects on cognition or mood were found. Intoxication was generally described as mild.

Read the original research

Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients.

Multiple sclerosis (Houndmills, Basingstoke, England), 10(4), 434-41

View on PubMed ↗

Citation

Wade, Derick T; Makela, Petra; Robson, Philip; House, Heather; Bateman, Cynthia. (2004). Do cannabis-based medicinal extracts have general or specific effects on symptoms in multiple sclerosis? A double-blind, randomized, placebo-controlled study on 160 patients.. Multiple sclerosis (Houndmills, Basingstoke, England), 10(4), 434-41.