Background: Evidence of cannabinoids’ analgesic efficacy is scant and largely anecdotal. How do efficacy and side effects of nabilone, a synthetic cannabinoid, compare with those of dihydrocodeine for chronic neuropathic pain?

Design and Participants: This was a randomized, double-blind, crossover trial comparing dihydrocodeine and nabilone. Patients with chronic neuropathic pain greater than 40.0 mm on a 0- to 100-mm visual analog scale (VAS) were randomized to receive up to 240 mg dihydrocodeine or 2 mg nabilone daily in two 6-week treatment periods separated by a 2-week washout period. Participants recorded average daily pain score, hours of sleep, sleep interruptions, amount of study drug taken, and side effects. The primary outcome was difference between the analgesic effect of nabilone vs. dihydrocodeine, measured by mean pain VAS score in the last 2 weeks of each treatment period. Secondary outcomes were change in mood, quality of life, sleep, and psychometric function. Participants (N = 96) had a mean age of 50 years (SD, 14); 48% were female; mean pain duration was 76 months (SD, 69); mean baseline pain VAS score was 70 mm (range, 29-95).

Results: Dihydrocodeine was a significantly better analgesic than nabilone. Mean VAS score at 6 weeks was 6.0 mm higher in the nabilone group than in the dihydrocodeine group (95% CI, 10.5-1.4, P = .01) for the available case analysis and 5.6 mm (95% CI, 10.3-0.8, P = .023) higher for the per-protocol analysis. Secondary outcomes were in alignment with primary outcomes. Side effects, though mild, were more frequent with nabilone. No patient responded to both drugs; 49 patients had no clinically relevant drop in pain score on either treatment.

Commentary: Cannabinoids are ineffective for acute pain, are relatively weak analgesics for peripheral neuropathies, and have the strongest evidence as an analgesic class for central neuropathic pain syndromes.1,2 This is the first double-blind randomized controlled trial (RCT) (which also included a crossover design) to compare nabilone with an opioid. The dose of nabilone was titrated to 2 mg/day, which is generally an acceptable dosing strategy to minimize toxicity, and the 6-week duration of treatment for each drug was a good compromise between adequate time to achieve some measure of efficacy without significant patient attrition. The results are rather disappointing. Dihydrocodeine is a weak opioid, compared to tramadol and potent mu agonists, and yet in treatment for neuropathic pain, its effect was superior to nabilone. There is evidence that the combination of a cannabinoid plus opioid is better than either one alone, and it is also reasonable to assume that central neuropathic pain syndromes (which were not well represented in this study) would have responded better to nabilone than peripheral neuropathies.2

Bottom Line: Weak opioids are superior to nabilone in the management of peripheral neuropathies.

Note: An RCT of cannabis cigarettes vs. placebo for HIV-associated neuropathic pain is reviewed in PC-FACS Issue 21 (April 2007), available online.

Reviewer: Mellar P. Davis, MD FCCP, The Cleveland Clinic, Cleveland, OH

Source: Frank B, Serpell MG, Hughes J, Matthews JNS, Kapur D. Comparison of analgesic effects and patient tolerability of nabilone and dihydrocodeine for chronic neuropathic pain: a randomised, crossover, double blind study. BMJ. 2008;336:199-201. To access the abstract of this article, link to NLM–PubMed here.

References:

1. Davis MP. Oral nabilone capsules in the treatment of chemotherapy-induced nausea and vomiting and pain. Expert Opin Investig Drugs. 2008;17:85-95.

2. Finnerup NB, Otto M, McQuay HJ, et al. Algorithm for neuropathic pain treatment: an evidence-based proposal. Pain. 2005;118:289-305.