A newly updated review suggests that there is limited evidence to support the use of cannabis-based medications for chronic neuropathic pain.

Investigators analyzed 21 clinical trials involving more than 2100 adult participants and examined three categories of cannabis-based medications: products high in tetrahydrocannabinol (THC), those primarily containing cannabidiol (CBD), and combination formulations with comparable amounts of both. The researchers found no high-quality evidence that any of these treatments reduced neuropathic pain more effectively than a placebo over follow-up periods ranging from 2 to 26 weeks.

Some small improvements were self-reported by patients who used combination products, but “these changes were not large enough to be considered clinically meaningful,” the investigators noted in a release.

Study investigator Winfried Häuser, MD, Technische Universität München, München, Germany, said in the release that well-designed studies are needed that are larger, include participants with comorbid physical and mental health conditions, and have treatment durations of at least 12 weeks.

“At present, the quality of most of the trials is too poor to draw firm conclusions,” Häuser added. 

The findings were published online on January 18 in the Cochrane Database of Systematic Reviews.

Updated Evidence

Population-based estimates suggest that 6%-10% of people experience chronic pain with neuropathic components, but existing pharmacologic treatments are often ineffective, the researchers noted

In light of increasing media promotion of cannabis for chronic pain, the researchers updated a review originally published in 2018.

The current analysis included 21 randomized, double-blind trials from three continents that compared placebo to medical cannabis, plant-derived cannabinoids, and synthetic cannabinoids for the treatment of neuropathic pain that lasted at least 2 weeks. 

Among the 21 studies (n = 2187; mean age range, 34-61 years), 15 were carried over from the 2018 review, and six were new. Seven studies evaluated THC-dominant products, five focused on CBD-dominant products, and nine assessed combined CBD-THC formulations. 

Outcomes included self-reported pain relief, a rating of “much” or “very much” improved on the Patient Global Impression of Change (PGIC), serious adverse events (AEs), and AE-related withdrawals.

No Robust Evidence

In the studies that compared THC-dominant products to placebo, there was “no clear evidence for effect” on pain relief of at least 30% (risk difference [RD], 0.16) or 50% (RD], 0.14), as well as for improved PGIC ratings (RD, 0.17), withdrawals due to AEs (RD, 0.03), serious AEs (RD, 0.02), and psychiatric disorder-related AEs (RD, 0.01).

Additionally, all findings were considered to have low-certainty evidence.

There was also no clear evidence that THC-CBD combination products were more effective than placebo for pain relief of at least 50% (RD, 0.04) or serious AEs (RD, 0.01), with both outcomes showing low-certainty evidence.

There were reports of improved PGIC ratings and pain relief of at least 30% (RD for both, 0.07), along with fewer AE-related withdrawals (RD, 0.05), but it all had low-certainty evidence, and the effects were not deemed to be clinically relevant.

For CBD-dominant medicines vs placebo, no clear evidence was found for an effect on pain relief of at least 50% (RD, -0.08).

The investigators noted “they may increase or decrease” PGIC improvement ratings, (RD, -0.03), withdrawals due to AEs (RD, 0.02), serious AEs (RD, 0.02), pain relief of at least 30% (RD, -0.04), nervous system-related AEs (RD -0.03), and psychiatric disorder-related AEs (RD -0.01); however, all had low-certainty evidence.

“Due to a lack of robust evidence, the benefits and harms of cannabis-medicines are unclear,” the researchers wrote.

They added that the overall evidence “was limited in both methodological rigor and clinical relevance.”

The investigators reported several financial relationships and/or potential conflicts, which are fully listed in the original article.