THC/CBD Spray Helped Some Patients with Treatment-Resistant Nerve Pain | Research

The takeaway

In a trial of 246 patients with peripheral neuropathic pain, THC/CBD spray achieved a meaningful pain response in significantly more patients than placebo, with additional benefits for sleep quality.

Read this if you have nerve pain and want to know whether cannabis-based medicines could help.

Significant 30% pain response rate and sleep quality improvement vs. placebo

What the researchers found

At the 30% pain reduction threshold (considered clinically meaningful), significantly more patients on THC/CBD spray achieved this target compared to placebo (p=0.034). The mean pain score reduction was numerically larger in the THC/CBD group but did not reach statistical significance on the continuous measure.

Secondary outcomes provided additional support: sleep quality improved significantly in the THC/CBD group (p=0.0072), and patients rated their overall condition as significantly more improved on the Subject Global Impression of Change (p=0.023).

Importantly, these patients had peripheral neuropathic pain with allodynia (pain from normally non-painful touch) and were already on analgesic therapy, making them a treatment-resistant population where any additional benefit is clinically relevant.

Why it matters

Peripheral neuropathic pain with allodynia is notoriously difficult to treat. Current medications provide inadequate relief for many patients. This trial demonstrates that THC/CBD spray can provide meaningful additional pain relief in a subset of otherwise treatment-resistant patients.

The numbers in context

303 screened, 246 randomized (128 THC/CBD, 118 placebo). 30% responder rate: significant (p=0.034, 95% CI: 1.05-3.70). Sleep quality: significant (p=0.0072). SGIC: significant (p=0.023). Mean pain score change: not significant.

How the study worked

This 15-week randomized, double-blind, placebo-controlled parallel group study enrolled 303 patients with peripheral neuropathic pain and allodynia. 128 received THC/CBD spray and 118 received placebo as add-on therapy to their current analgesic regimen. Co-primary endpoints were the 30% responder rate and mean change in pain scores on a 0-10 numerical rating scale.

What this study cannot tell us

The mean pain score change was not statistically significant, with only the responder analysis reaching significance. This suggests the benefit is concentrated in a subgroup rather than uniform across all patients. The 15-week duration may not capture long-term effects. The relatively high placebo response rate reduced the apparent treatment effect.

How to read the evidence

This is a well-designed, adequately powered Phase III RCT. The mixed results (significant responder rate but non-significant mean change) provide strong but nuanced evidence.

When this study was published

Published in 2014. THC/CBD spray (Sativex) has since been approved in several countries for various pain conditions.

The bigger picture

Neuropathic pain affects millions of people and responds poorly to standard painkillers. This trial adds to the evidence that cannabinoid-based medicines can benefit a meaningful proportion of these patients, even though the average effect across all patients may appear modest.

Questions still open

Can the responding subgroup be identified before treatment to improve prescribing? What is the long-term efficacy and does tolerance develop? Would higher doses produce greater pain relief or only more side effects?

Common questions

What is allodynia?

Allodynia is a condition where normally non-painful stimuli (like light touch or clothing against the skin) cause pain. It is common in peripheral neuropathic pain and makes the condition especially debilitating and difficult to treat.

Why was the mean pain score change not significant if the responder rate was?

This pattern suggests the drug works well for some patients but not others. When you average all patients together, the non-responders dilute the effect. The responder analysis captures the fact that a significantly larger proportion of treated patients achieved meaningful relief.

Read the original research

A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment.

European journal of pain (London, England), 18(7), 999-1012

View on PubMed ↗Publisher’s paper ↗

Citation

Serpell, M; Ratcliffe, S; Hovorka, J; Schofield, M; Taylor, L; Lauder, H; Ehler, E. (2014). A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment.. European journal of pain (London, England), 18(7), 999-1012. https://doi.org/10.1002/j.1532-2149.2013.00445.x