Cannabinoids for Neuropathic Pain: Do They Work?

Selective cannabinoids may provide limited relief from chronic neuropathic pain and improvements in quality of life and sleep with no major adverse effects, according to a systematic review and meta-analysis recently published in Anesthesia & Analgesia.¹

Howard Meng, MD, from the Department of Anesthesia and Pain Management at the University of Toronto, Canada, and colleagues reviewed the effects of selective cannabinoids vs conventional treatments or placebo on chronic neuropathic pain.

For this review, they searched MEDLINE, EMBASE, and other databases through March 2016 and performed a meta-analysis of numerical rating scale scores for neuropathic pain. The Grade of Recommendations Assessment was used to classify the certainty of evidence.

A total of 11 randomized controlled trials including 1219 patients (614 in the selective cannabinoid group and 605 in comparator groups) treated for periods ranging from 2 to 15 weeks were included in this study. Cannabinoids assessed were: dronabinol (also known as Δ9-tetrahydrocannabinol [THC]; 1 trial); nabilone, a synthetic cannabinoid that mimics THC (3 trials); and nabiximols (cannabis extract with THC and cannabidiol [CBD] as active ingredients; 7 trials).

Patients in the selective cannabinoids groups had a significant but clinically small reduction in pain vs the comparator group (-0.65 points on the 0 to 10 numeric rating scale; 95% CI: -1.06 to -0.23 points; P =.002, I₂ = 60%; Grade of Recommendations Assessment, Development, and Evaluation: weak recommendation and moderate-quality evidence).

The majority of reported adverse effects were mild to moderate, the most common including dizziness and lightheadedness, drowsiness, and dry mouth. Adverse effects usually occurred when treatment began and reduced over time, indicating that participants were developing tolerance.

Adverse events serious enough to require withdrawal from trials included confusion (2 patients on nabilone), headache (1 patient on nabilone), intolerance (4 patients on nabilone and 8 patients on dihydrocodeine used as a comparator treatment), and agitation and paranoid ideation (2 patients on selective cannabinoids).

“Daily doses of 2.5 to 10 mg of dronabinol, 1 to 4 mg of nabilone, and 8.3 sprays of nabiximols when administered over 2 to 15 weeks are associated with analgesic benefit compared [with] placebo at 2 weeks or more following initiation of treatment,” the researchers wrote.

However, “there was variability in the studies in quality of reporting, etiology of [neuropathic pain], type and dose of selective cannabinoids,” they noted. “Well designed, large, randomized studies are required to better evaluate specific dosage, duration of intervention, and the effect of this intervention on physical and psychologic function.”

Summary & Clinical Applicability

The researchers recommend that selective cannabinoids may be used as adjunct analgesics in patients with neuropathic pain (Grade: weak recommendation; moderate quality evidence).

In addition to providing mild pain relief, selective cannabinoids may also be associated with improvements in quality of life, sleep, patients’ impressions of positive change, and improved sensory and pain thresholds with psychometric testing.

Nabiximols and dronabinol, but not nabilone, provided pain relief in the trials included in this systematic review and meta-analysis.

“The overall small analgesic benefit and the adverse effects associated with use of selective cannabinoids should be discussed with patients and their preferences and values considered before prescribing selective cannabinoids,” the researchers concluded. “Further research in this field is justified because there is a lack of information about appropriate dosages and duration of treatment, impact of these medications on physical and psychologic functioning, and adverse effects.”

Limitations & Disclosures

• The researchers were unable to comment on the ideal proportions of THC and CBD in nabiximols because of the significant variation in the amounts used in the trials. The dose per administration and daily maximum limits also varied across the trials.
• Pain relief was assessed over a wide range of time periods after interventions were started.
• Diagnosis of neuropathic pain was primarily clinical, and measures such as qualitative sensory testing and validated questionnaires were not used consistently.
• The effect of selective cannabinoids on physical and psychological disability, sleep, and quality of life was not assessed rigorously in the trials.

Reference

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

This article originally appeared on Clinical Pain Advisor