San Diego—Those touting the panacea-like properties of cannabinoids may be disappointed by a recent study from Canada. The systematic review and meta-analysis of trials for chronic neuropathic pain has shown that cannabinoids provide only a modest analgesic benefit compared with conventional management or placebo.

According to the study’s authors, the moderate quality of evidence suggested that cannabinoids are effective in reducing central but not peripheral neuropathic pain.

“Based on these data, we can say cannabinoids have a statistically significant but clinically modest effect on chronic neuropathic pain,” said Howard Meng, MD, a resident in the Department of Anesthesia and Pain Management at Toronto Western Hospital, University of Toronto. “With this moderate quality of evidence, we can make a weak recommendation for the use of cannabinoids for treating neuropathic pain as a pain adjunct, not as a sole agent, and specifically for central neuropathic pain.”

As Dr. Meng reported at the 2016 annual meeting of the American Society of Regional Anesthesia and Pain Medicine (abstract 2909), management of chronic neuropathic pain with available pharmacotherapy is associated with a high failure rate.

“Given the void of effective therapy, there’s been an increase in use and popularity of cannabis and cannabinoid for treating this type of pain,” Dr. Meng said. “The concern that we have, however, is that recent pain guidelines provide contradictory recommendations.”

Systematic Review and Meta-Analysis
Using MEDLINE, Embase and other major databases, Dr. Meng and his colleagues reviewed randomized controlled trials (up to March 31, 2016) that compared cannabinoids (dronabinol [Marinol, AbbVie], nabilone [Cesamet, Meda] and nabiximols [Sativex, GW]) with conventional treatment or placebo in patients with chronic neuropathic pain. The researchers included 11 randomized controlled trials of 1,219 patients in total.

There was variability in the etiology of neuropathic pain, dose of cannabinoids, duration of trials and choice of adjunct analgesics, Dr. Meng reported. Before being treated with cannabinoids, patients were refractory to first- or second-line neuropathic pain agents.

When compared with placebo in patients with neuropathic pain, cannabinoids yielded a modest reduction of pain scores (mean difference, –0.65 points; 95% CI, –1.06, –0.23; P=0.002; I=60%).

Although there were no major adverse effects, cannabinoid users had increased nonserious side effects compared with placebo counterparts, said Dr. Meng, who noted that these effects subsided with time, “perhaps due to a buildup of tolerance.”

Additional analysis comparing specific cannabinoids showed that nabiximols had a significant effect, whereas nabilone did not. Nabiximols with cannabidiol (CBD) had a significantly better effect, Dr. Meng noted.

Finally, whereas analgesic efficacy of cannabinoids was shown in patients with central neuropathic, pain scale scores of trials in patients with peripheral neuropathic pain were not significant when compared with conventional treatment or placebo, perhaps due to the different mechanisms involved in these types of pain.

“Cannabinoids provide modest analgesic benefit in trials lasting two to 15 weeks in patients with chronic neuropathic pain,” Dr. Meng concluded.

The session moderator, Charles Berde, MD, PhD, division chief of pain medicine and pain treatment service at Boston Children’s Hospital, and professor of pediatric anesthesia at Harvard Medical School, in Boston, cited the promising research of cannabinoid pharmaceuticals by Mark Wallace, MD, professor of anesthesiology at the University of California, San Diego (UCSD) and program director at UCSD Center for Pain Medicine.

“Based on Dr. Wallace’s work,” Dr. Berde said, “I’m personally convinced that a pure pharmaceutical of CBD or CBD mixture, but not a predominant THC [tetrahydrocannabinol] mixture, might make sense as a pharmaceutical someday. Dronabinol is good for appetite and nausea, but it’s not very effective for pain.

“Dr. Wallace is obviously an advocate for cannabinoids,” Dr. Berde added, “but, regardless of what you think about their efficacy and long-term effects, his track record of getting people off opioids is compelling.”

—Chase Doyle

Drs. Meng and Berde reported no relevant financial disclosures.