A Cochrane review of 16 trials found cannabis-based medicines provide modest pain relief for neuropathic pain but with significant side effects | Research

The takeaway

A Cochrane review of 16 randomized trials (1,750 patients) found that cannabis-based medicines may increase 50% pain relief compared to placebo (21% vs 17%, NNT 20) for chronic neuropathic pain, but potential harms (nervous system disorders NNH 3, psychiatric disorders NNH 10) may outweigh benefits.

Pain medicine specialists; neurologists treating neuropathic pain; guideline developers; patients considering cannabis for nerve pain.

NNT of 20 for 50% pain relief; NNH of 3 for nervous system side effects

What the researchers found

The Cochrane Collaboration reviewed 16 randomized, double-blind controlled trials (1,750 patients, 2-26 weeks) of cannabis-based medicines for chronic neuropathic pain.

Formulations included: THC/CBD oromucosal spray (10 studies), nabilone (2), inhaled herbal cannabis (2), and dronabinol (2).

Efficacy was modest: 21% of cannabis patients achieved 50% or greater pain relief vs 17% with placebo (NNT 20, low-quality evidence). For 30% pain relief: 39% vs 33% (NNT 11, moderate-quality evidence).

Harms were notable: 10% discontinued due to adverse events vs 5% on placebo (NNH 25). Nervous system adverse events occurred in 61% vs 29% (NNH 3). Psychiatric disorders occurred in 17% vs 5% (NNH 10).

The authors concluded that "potential benefits might be outweighed by potential harms" and noted that study populations excluded people with substance abuse history and significant comorbidities, limiting real-world applicability.

Why it matters

Cochrane reviews are considered the gold standard of evidence synthesis. This review's conclusion that harms may outweigh benefits for neuropathic pain is a significant counterpoint to the enthusiastic promotion of cannabis for chronic pain. The NNT of 20 for 50% pain relief is notably worse than many existing pain treatments.

The numbers in context

16 trials, 1,750 patients. 50% pain relief: 21% vs 17%, NNT 20 (low quality). 30% pain relief: 39% vs 33%, NNT 11 (moderate quality). Adverse event withdrawal: NNH 25. Nervous system AEs: 61% vs 29%, NNH 3. Psychiatric AEs: 17% vs 5%, NNH 10.

How the study worked

Cochrane systematic review and meta-analysis. 16 RCTs, 1,750 participants. Random-effects model. GRADE quality assessment. NNT and NNH calculations. Quality ranged from low to high across studies.

What this study cannot tell us

Most studies used THC/CBD spray (Sativex), limiting generalizability to other cannabis products. Study populations excluded substance abuse and significant comorbidities. Short trial durations (2-26 weeks). No long-term safety data available.

How to read the evidence

Strong. Cochrane systematic review with GRADE quality assessment, the highest level of evidence synthesis, though limited by the quality of underlying trials.

When this study was published

Published in 2018. This remains one of the most-cited reviews on cannabis for neuropathic pain.

The bigger picture

This Cochrane review provides the most rigorous evidence assessment to date on cannabis for neuropathic pain. The modest efficacy combined with significant side effects suggests cannabis-based medicines should be positioned as a later-line option rather than a first-choice treatment for neuropathic pain.

Questions still open

Would specific neuropathic pain subtypes respond better? Do inhaled cannabis and oral products have different efficacy profiles? What is the long-term safety profile for chronic neuropathic pain use? How do cannabis medicines compare head-to-head with existing neuropathic pain treatments?

Common questions

What does NNT of 20 mean?

Number needed to treat (NNT) of 20 means that 20 patients need to be treated with cannabis-based medicine instead of placebo for one additional patient to achieve 50% pain relief. Lower NNTs indicate more effective treatments. For comparison, some existing neuropathic pain drugs have NNTs of 4-7.

Does this mean cannabis does not work for pain?

Cannabis-based medicines showed statistically significant pain relief compared to placebo, so they do "work" to some degree. The concern is that the benefit is modest (NNT 20) while the side effects are frequent (61% had nervous system effects). For some patients the benefit may be worthwhile, but on a population level, harms may outweigh benefits.

Read the original research

Cannabis-based medicines for chronic neuropathic pain in adults.

The Cochrane database of systematic reviews, 3(3), CD012182

View on PubMed ↗Publisher’s paper ↗

Citation

Mücke, Martin; Phillips, Tudor; Radbruch, Lukas; Petzke, Frank; Häuser, Winfried. (2018). Cannabis-based medicines for chronic neuropathic pain in adults.. The Cochrane database of systematic reviews, 3(3), CD012182. https://doi.org/10.1002/14651858.CD012182.pub2