Sativex Significantly Reduced Neuropathic Pain and Allodynia in a Controlled Trial | Research

The takeaway

A THC/CBD mouth spray reduced neuropathic pain nearly three times more than placebo, and a follow-up study showed the benefit lasted a full year without dose escalation.

Read this if you have neuropathic pain and want to understand the clinical trial evidence for cannabis-based treatments.

-1.48 vs. -0.52 point pain reduction (p=0.004), sustained for 52 weeks

What the researchers found

In a five-week randomized trial, 125 patients with peripheral neuropathic pain received either Sativex (THC:CBD mouth spray) or placebo while continuing their existing pain medications.

Patients on Sativex experienced significantly greater pain reduction: -1.48 points vs. -0.52 points on a 0-10 pain scale (p=0.004). The treatment also improved sleep (p=0.001), reduced both dynamic and punctate allodynia (pain from normally non-painful touch), and lowered pain-related disability (p=0.003).

Patient-reported global improvement strongly favored Sativex (p<0.001). However, 18% of Sativex patients withdrew due to side effects (mainly sedation and GI issues) compared to 3% on placebo.

An open-label extension study showed that pain relief was maintained for 52 weeks without dose escalation or toxicity, suggesting no tolerance developed.

Why it matters

Neuropathic pain is notoriously difficult to treat, and allodynia (pain from gentle touch) is one of its most debilitating features. This trial showed Sativex addressed both general neuropathic pain and allodynia specifically, with sustained benefit over a year.

The numbers in context

Pain reduction: -1.48 vs. -0.52 points (p=0.004). Sleep improvement: p=0.001. Dynamic allodynia: p=0.042. Punctate allodynia: p=0.021. Disability index: p=0.003. Withdrawal due to adverse events: 18% Sativex vs. 3% placebo. 52-week extension showed maintained benefit.

How the study worked

Randomized, double-blind, placebo-controlled, parallel design trial over 5 weeks. 125 patients with peripheral neuropathic pain self-titrated their Sativex dose while maintaining existing analgesics. Primary outcome was change in daily pain intensity on a 0-10 numerical rating scale. An open-label extension followed for up to 52 weeks.

What this study cannot tell us

The five-week controlled phase was relatively short. The open-label extension lacked a placebo control, so sustained benefit could partly reflect placebo effects or natural disease fluctuation. The 18% withdrawal rate on Sativex suggests tolerability challenges for some patients.

How to read the evidence

This is a well-designed randomized, double-blind, placebo-controlled trial with a substantial open-label extension, providing strong evidence for Sativex in neuropathic pain.

When this study was published

Published in 2007. Sativex has since received regulatory approval in multiple countries for MS-related symptoms and is used off-label for neuropathic pain.

The bigger picture

This study was part of the clinical evidence base that supported Sativex's regulatory approval in multiple countries. The demonstration that cannabinoid-based treatment could provide sustained neuropathic pain relief without tolerance was particularly important given concerns about long-term cannabinoid use.

Questions still open

Which neuropathic pain conditions respond best to Sativex? Can the side effect profile be improved through dosing strategies? How does Sativex compare directly to existing neuropathic pain medications?

Common questions

What is allodynia?

Allodynia is pain caused by stimuli that normally would not be painful, such as light touch or gentle pressure. It is a hallmark of neuropathic pain and significantly impacts quality of life.

Did patients need to keep increasing their dose?

No. The 52-week extension study found that the dose remained stable over time with no evidence of tolerance, meaning patients did not need more medication to achieve the same level of pain relief.

Read the original research

Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial.

Pain, 133(1-3), 210-20

View on PubMed ↗

Citation

Nurmikko, Turo J; Serpell, Mick G; Hoggart, Barbara; Toomey, Peter J; Morlion, Bart J; Haines, Derek. (2007). Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial.. Pain, 133(1-3), 210-20.