Cannabis Sprays Reduced Nerve Pain from Brachial Plexus Injury | Research

The takeaway

A randomized trial found that cannabis-based sprays (Sativex and THC-only) produced statistically significant pain improvements in 48 patients with brachial plexus nerve pain, though the improvements did not meet the predefined two-point clinical significance threshold.

Read this if you have nerve pain that has not responded to other treatments and want to know about cannabis-based options.

Statistically significant pain and sleep improvement in treatment-resistant nerve pain

What the researchers found

In 48 patients with chronic nerve pain from brachial plexus root avulsion, both Sativex (THC:CBD approximately 1:1) and a THC-only extract delivered by oral spray produced statistically significant improvements in pain severity compared to placebo during two-week treatment periods. Sleep measures also improved significantly.

However, the primary outcome (mean pain severity over the last 7 days) did not fall by the two points defined in the study hypothesis as clinically meaningful, placing this in the category of statistically significant but not clinically significant by the researchers' own predefined standard. The medications were generally well tolerated, with most adverse events being mild to moderate.

Why it matters

Brachial plexus avulsion pain is an excellent model of central neuropathic pain because the injury is anatomically uniform. All patients had intractable symptoms on current analgesics, making this a treatment-resistant population. The finding of statistical significance despite the predefined clinical threshold not being met raised important questions about outcome definition in chronic pain research.

The numbers in context

Forty-eight patients enrolled. Baseline pain score 4+ on 11-point scale. Two-week treatment periods. Both active treatments showed statistically significant improvement. Predefined two-point clinical significance threshold not met.

How the study worked

This was a randomized, double-blind, placebo-controlled, three-period crossover study. Forty-eight patients with at least one avulsed brachial plexus root and baseline pain score of 4+ (out of 11) received placebo, Sativex (THC:CBD), or THC-only extract via oromucosal spray in random order, each for two weeks following a two-week baseline.

What this study cannot tell us

Two-week treatment periods may have been too short for full therapeutic effect in chronic pain. The predefined two-point threshold for clinical significance was ambitious for a pain population already on analgesics. The crossover design could be affected by carryover effects.

How to read the evidence

This is a well-designed randomized, double-blind, placebo-controlled crossover trial with 48 patients, providing moderate-level evidence.

When this study was published

Published in 2004. Sativex was subsequently approved for neuropathic pain in some jurisdictions.

The bigger picture

This trial contributed to the evidence base for Sativex in neuropathic pain. While the primary outcome was technically not met, the combination of statistical significance, sleep improvement, and good tolerability in a treatment-resistant population supported continued development. Sativex was later approved for MS-related neuropathic pain in some jurisdictions.

Questions still open

Would longer treatment periods produce larger pain improvements? Was the two-point threshold too stringent for treatment-resistant neuropathic pain? How do these results compare to other treatments for brachial plexus pain?

Common questions

Can cannabis help with nerve pain?

This trial found statistically significant improvements in neuropathic pain from brachial plexus injury with cannabis-based sprays. While the improvement was modest, it was meaningful for patients who had not responded to other pain treatments.

What is the difference between statistical and clinical significance?

Statistical significance means the result was unlikely due to chance. Clinical significance means the improvement is large enough to matter to patients. This trial achieved the former but not the latter by the researchers' own predefined standard of a two-point reduction on an 11-point scale.

Read the original research

Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial.

Pain, 112(3), 299-306

View on PubMed ↗Publisher’s paper ↗

Citation

Berman, Jonathan S; Symonds, Catherine; Birch, Rolfe. (2004). Efficacy of two cannabis based medicinal extracts for relief of central neuropathic pain from brachial plexus avulsion: results of a randomised controlled trial.. Pain, 112(3), 299-306. https://doi.org/10.1016/j.pain.2004.09.013