Can an Oromucosal Spray of THC-CBD Reduce Chronic Neuropathic Pain?

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Digitally generated close up Neurons cells
Researchers conducted a meta-analysis of double-blind RCTs of nabiximols and placebo treatments for chronic, noncancer neuropathic pain.

Noncancer-related chronic neuropathic pain may be effectively reduced by treatment with a mixture of tetrahydrocannabinol (THC) and cannabidiol (CBD), but additional large clinical trials are needed to assess the true impact of the medication on this condition. These results were published in the journal Pain Medicine.

Nabiximols (Sativex® oromucosal spray, GW Pharmaceuticals/Jazz Pharmaceuticals) — a complex, botanical mixture of THC and CBD with other cannabinoid and noncannabinoid components — is approved in certain countries, not including the United States, as an add-on therapy for people with chronic neuropathic pain who have inadequate relief from opioids and other analgesics. While numerous systematic reviews and meta-analyses have evaluated both cannabis and cannabinoid-related products (including nabiximols) for chronic pain management, no published reports to date have specifically reviewed the role of nabiximols in chronic neuropathic pain.

Researchers therefore conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) of nabiximols and placebo treatments for chronic, noncancer neuropathic pain. Inclusion was restricted to double-blind RCTs.

The meta-analysis included 9 RCTs with a total of 1289 patients (633 treated with nabiximols and 656 who received placebo). Included patients had neuropathic pain of various etiologies, including multiple sclerosis or other neurological defects, spinal cord injury, brachial plexus avulsion, postherpetic neuralgia, peripheral neuropathy, radiculopathy, complex regional pain syndrome type II, postherpetic neuralgia, peripheral neuropathy, focal nerve lesion, and diabetes. Seven studies had parallel group designs and 2 were crossover studies.

Mean study duration was 7.2 weeks. The maximum allowed dosage of nabiximols was 12 to 48 sprays per day (mean dosage, 8-10.9 sprays per day). Patients were permitted to continue treatment with any underlying analgesic medication, with treatment and control groups generally well-matched for concurrent medication. Baseline pain severity was moderate in all studies.

Results of a meta-regression showed no correlation of efficacy with either treatment duration (correlation coefficient [r]=−0.04; P =.386; R2=10.9%) or maximum daily dosage (r=0.01; P =.659; R2=10.9%).

A pooled endpoint for change in pain scores was significantly in favor of nabiximols over placebo; effect size estimate was −0.40 (95% CI, −0.59 to −0.21) in a fixed effect model and −0.44 (95% CI, −0.70 to −0.19) in a random effects model. Statistical heterogeneity was deemed not important (I2=39%).

Nabiximols were associated with a small but significant treatment effect across studies. Standardized mean difference was −0.21 (95% CI, −0.32 to-−0.10) in the fixed effect model and −0.26 (95% CI, −0.42 to −0.10) in the random effects model, with moderate statistical heterogeneity (I2=43%).

Sensitivity analysis of effect size estimates for change in pain scores favored nabiximols over placebo for indications of MS or other underlying condition, central or peripheral chronic neuropathic pain, treatment duration ≤6 weeks or >6 weeks, and maximum allowed daily dosage of nabiximols.

Study limitations include the short treatment period in some studies and population heterogeneity in terms of the underlying chronic pain condition.

The results of this analysis suggest that therapy with nabiximols oromucosal spray for chronic noncancer neuropathic pain refractory to usual treatments may be associated with a treatment effect, although not yet statistically significant.

“The emergent message is that individualized RCTs should generally be larger and adequately powered to show a statistically significant effect,” they concluded. “At present, additional larger RCTs specifically designed to assess the effect of nabiximols in neuropathic pain are required” in order to enable more definitive conclusions to be reached.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Dykukha I, Malessa R, Essner U, Überall MA. Nabiximols in chronic neuropathic pain: A meta-analysis of randomized placebo-controlled trials. Pain Med. 2021;22(4):861-874.

This article originally appeared on Clinical Pain Advisor