Cannabis-Based Spray Significantly Reduced MS Central Pain and Sleep Problems in Rigorous Trial | Research

The takeaway

A randomized controlled trial of 66 MS patients found THC:CBD oromucosal spray significantly reduced central neuropathic pain intensity (P = 0.005) and sleep disturbance (P = 0.003) compared to placebo, with 97% of patients completing the trial.

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

Pain reduced by 2.7 points on the active treatment vs 1.4 on placebo (P = 0.005)

What the researchers found

Sixty-six MS patients with central pain (59 with dysesthetic pain, 7 with painful spasms) participated in a 5-week randomized, double-blind, placebo-controlled trial of a THC:CBD oromucosal spray. Each spray delivered 2.7 mg THC and 2.5 mg CBD, with patients self-titrating up to 48 sprays per day.

Sixty-four patients (97%) completed the trial. In week 4, those on the active medication used an average of 9.6 sprays daily compared to 19.1 for placebo, suggesting participants recognized the active treatment and adjusted their dosing.

The cannabis-based medicine was significantly superior to placebo for both pain intensity (mean change -2.7 vs -1.4, P = 0.005) and sleep disturbance (mean change -2.5 vs -0.8, P = 0.003) on 11-point rating scales. The treatment was generally well tolerated, with dizziness, dry mouth, and somnolence being more common in the active group. Cognitive side effects were limited to long-term memory storage.

Why it matters

Central pain in MS is common and often resistant to existing treatments. This trial demonstrated clinically meaningful pain relief and sleep improvement with a cannabis-based medicine, with the high completion rate (97%) indicating good tolerability. Published in Neurology, it provided high-quality evidence for regulatory decisions.

The numbers in context

66 patients enrolled. 64 (97%) completed. 34 received active treatment. Mean daily sprays: 9.6 active vs 19.1 placebo. Pain reduction: -2.7 vs -1.4 (P = 0.005). Sleep improvement: -2.5 vs -0.8 (P = 0.003). Side effects: dizziness, dry mouth, somnolence.

How the study worked

Single-center, 5-week (1-week run-in, 4-week treatment), randomized, double-blind, placebo-controlled, parallel-group trial. Sixty-six MS patients with central pain received THC:CBD oromucosal spray (2.7 mg THC + 2.5 mg CBD per spray) or placebo as adjunctive analgesic treatment. Self-titration up to 48 sprays/24 hours. Pain and sleep measured daily on 11-point numerical rating scales.

What this study cannot tell us

Single center with 66 patients. The large difference in placebo spray usage (19.1 vs 9.6 daily sprays) suggests possible unblinding, as active treatment participants may have recognized the drug effects. Four-week treatment period may not capture long-term efficacy or safety. Published in Neurology, a high-impact journal.

How to read the evidence

Well-designed randomized, double-blind, placebo-controlled trial published in a top neurology journal. High completion rate and statistically significant results. Possible unblinding suggested by spray usage differences.

When this study was published

Published in 2005 in Neurology. This trial contributed to subsequent Sativex approvals for MS-related symptoms in multiple countries.

The bigger picture

This trial was part of the clinical development program that led to Sativex's regulatory approvals. The focus on central neuropathic pain, a condition particularly resistant to conventional analgesics, positioned cannabis-based medicines as a treatment option where alternatives were limited.

Questions still open

Does the pain relief persist with long-term use, or does tolerance develop? How does this compare to other neuropathic pain treatments in terms of effect size?

Common questions

How effective was the cannabis spray for MS pain?

Patients using the THC:CBD spray had their pain reduced by an average of 2.7 points on an 11-point scale, compared to 1.4 points for placebo. This difference was statistically significant (P = 0.005) and clinically meaningful.

Were there significant side effects?

The treatment was generally well tolerated, with dizziness, dry mouth, and somnolence being more common than placebo. Cognitive side effects were limited to long-term memory storage. Ninety-seven percent of patients completed the full trial.

Read the original research

Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis.

Neurology, 65(6), 812-9

View on PubMed ↗

Citation

Rog, David J; Nurmikko, Turo J; Friede, Tim; Young, Carolyn A. (2005). Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis.. Neurology, 65(6), 812-9.