Selective Cannabinoids: A Potential Adjuvant for Chronic Neuropathic Pain?

Neuropathic pain is an elusive target for anesthesia pain specialists. A small class of anti-epileptic and antidepressant mediations has been the mainstay of medical therapy for neuropathic pain, and it has been put forward that only one in three patients who suffer from this particularly recalcitrant condition has an analgesic response to treatment.

In searching for potential new therapies for neuropathic pain, selective cannabinoids (synthetic cannabinoids containing only tetrahydrocannabinol [THC]) have emerged in the past decade as a drug class of interest. Cannabinoid receptors play a role in pain modulation by inhibiting pain responses, and also interact with various other receptor systems such as GABA, opiate, serotonergic and adrenergic, many of which are current targets for neuropathic pain medications.

A recent meta-analysis attempted to examine the efficacy of selective cannabinoids in treating neuropathic pain refractory to first and second-line agents. A database search was conducted for randomized control trials (RCT) comparing selective cannabinoids (dronabinol, nabilone, and nabiximols) containing synthetic THC, or a combination of extracted THC and CBD, versus placebo or standard treatment.

Selective Cannabinoids11 RCTs were selected for inclusion. All studied neuropathic pain patients, but there was variability in the etiology of this pain and its distribution. Variation also existed in which cannabinoid was used (1 dronabinol trial, 3 nabilone, and 7 nabiximols) and for how long (2 to 15 weeks), as well as the dosages. Primary outcome in all studies was pain score, with a multitude of secondary outcomes including physical function, quality of sleep, anxiety, and patient satisfaction. Not all secondary outcomes were examined across all studies (e.g. only three included physical function).

Metanalysis of the 11 RCTs showed that with regard to the primary outcome of pain scores (measured on the numerical rating scale and measured at least two weeks after therapy initiation), there was a statistically significant but clinically small reduction in pain scores in the selective cannabinoids group (mean difference −0.65 points; 95% CI, −1.06 to −0.23 points; P = .002, I2 = 60%).

For secondary outcomes, quality of sleep and patient satisfaction were significantly improved. Only one of the three studies that examined physical function reported an improvement. Six out of the seven studies that examined quality of sleep found an improvement. Only one of the three studies that examined anxiety reported an improvement. Five of the six studies that examined patient satisfaction reported positive results.

Adverse effects of selective cannabinoids studied by the 11 included RCTs were mostly mild to moderate. Most common were dizziness/lightheadedness, somnolence, and dry mouth. Rarely there were severe adverse effects requiring withdrawal from the trials: confusion (2 patients), headache (1 patient), agitation and paranoid ideation (2 patients).

Overall, the small clinical reduction in pain scores must be weighed against the potential for adverse effects. Sleep quality and patient satisfaction are likely secondary benefits. Weaknesses of this meta-analysis include wide heterogeneity of trials and likely publication bias. Further research is needed to standardize dosages and duration of treatment, as well as better define adverse effects.

References

  1. Meng H, Johnston B, Englesakis M, Moulin DE, Bhatia A. Selective cannabinoids for chronic neuropathic pain: a systematic review and meta-analysis [published online May 19, 2017]. Anesth Analg. doi:10.1213/ANE.0000000000002110