Cannabis Gaining Acceptance as Treatment for Neuropathic Pain?

Pauline Anderson

June 02, 2020

Experts may be moving toward accepting cannabis as a useful tool to treat neuropathic pain (NP), a recent debate on the topic suggests.

During the debate, one expert argued for, and another against, there being sufficient evidence for the use of cannabis to treat neuropathic pain, but in the end, they agreed that some patients do benefit.

The discussion took place at the Congress of the European Academy of Neurology (EAN) 2020, which transitioned to a virtual online meeting because of the COVID-19 pandemic.

The cannabis plant has 460 constituents. The two main components are tetrahydrocannabinol (THC) and cannabidiol (CBD). It can be consumed by swallowing oil extracts, by the sublingual route, or by smoking or eating the plant. Cannabis medications already in use include oral THC (nabilone, dronabinol) and an oral mucosal spray (nabiximols [Sativex]).

Arguing that therapeutic cannabis is helpful for neuropathic pain, Elon Eisenberg, MD, professor of neurology and pain medicine, Israel Institute of Technology, Haifa, cited a number of encouraging randomized controlled trials (RCTs) and meta-analyses of studies on the subject.

Opioid Substitute

He discussed three relevant articles. One was a 2016 viewpoint article published in JAMA that concluded that "cannabis seems to be a substitute, a rather good one, for opioids," said Eisenberg.

A "comprehensive" 440-page review, published by the National Academies Press in 2017, evaluated the evidence to that point and "came to the conclusion there is substantial evidence that cannabis is an effective treatment for chronic pain in adults," said Eisenberg.

And a 2018 position paper from the European Pain Federation determined that "the quantity and quality of evidence is such that cannabis-based medicines may be reasonably considered for chronic neuropathic pain," he said.

He noted that the most recent results from an Israeli prospective cohort registry study that is following more than 851 patients who are taking cannabis over a year are positive. Analyses show a steady reduction in pain intensity and improvements in catastrophizing and disability. Importantly, he said, participants are using fewer opioids.

However, about 40% of patients in that registry study experienced some adverse event, although most were not serious, said Eisenberg

Not Convinced

Arguing on the other side ― that therapeutic cannabis is not helpful for neuropathic pain ― was Nadine Attal, MD, PhD, professor of therapeutics and pain at the University Versailles Saint Quentin, France.

She questioned the quality of some of the research to date and stressed that studies should consider NP as a primary outcome ― not spasticity or pain in general. They should also be double-blind, randomized, and placebo controlled, she said.

In addition, she said these studies should enroll at least 10 patients per group and should continue for 3 weeks or longer.

Attal wondered which of the many plant derivatives (phytocannabinoids) are used in cannabis studies.

She discussed four meta-analyses or reviews on the topic, some of which she said are "heterogeneous" and don't provide convincing evidence for cannabis use in NP.

For example, one review only examined marijuana, and all studies in it were short term. One of the studies in this review was of spasticity.

Another review included two studies of cancer pain, and the most positive study in NP used short-term inhaled THC.

"There is no evidence to date that cannabinoids, including nabiximols or oral THC, administered for at least 3 weeks are more effective than placebo in neuropathic pain," she concluded.

Some Responders

However, Attal acknowledged that cannabis might be effective for some patients. In her experience, which has been borne out by some observational studies, patients with paroxysmal pain, or sudden stabbing pain, seem to get more relief from cannabis.

"It's absolutely possible that there's a subgroup of symptoms or a subgroup of patients with specific symptoms who are much better responders to cannabis than others," she said.

Asked if patients experience increased pain after withdrawing from cannabis, Eisenberg said he has observed that many patients stop taking cannabis when they start feeling better, but he hasn't seen severe withdrawal symptoms.

However, there are other concerns related to cannabis use, said Eisenberg.

A major concern regards driving a vehicle. In Israel, getting behind the wheel is prohibited within 6 hours of using cannabis.

But Eisenberg pointed out that published data on the safety of cannabis and driving were based on recreational users. "We need to keep in mind that recreational users typically use other substances, so we're not sure the data is accurate," he said.

There are increasing reports of stroke, transient ischemic attack, and myocardial infarction among cannabis users. This is especially concerning because many of these cases involve young male adults who have no risk factors, said Eisenberg.

One delegate asked whether legal issues make it difficult to properly investigate cannabis in large studies.

Eisenberg noted that legal concerns may help explain why there have not been any new RCTs for about 2 years.

"In the US, you can't do clinical trials; cannabis is still regarded as schedule I substance," he said.

Some physicians "are reluctant to deal with cannabis unless they get better data," he said. "Doing research on cannabis seems to be somehow out of the mainstream."

Moreover, the research is difficult to carry out, owing to the complexity of the cannabis plant, which has many constituents. Perhaps it's a matter of identifying and adding particular components to better demonstrate reduced pain, said Eisenberg.

Another complicating factor is that bioavailability differs considerably from one patient to another, "sometimes even by 10-fold," he said.

Attal's group will be starting a study next January that will enroll a large sample of patients with neuropathic pain or spasticity. In that study, cannabis will be dispensed through pharmacies and primary care. The aim of the study is "to see how it works in a real-life setting," she said

Those participating in the virtual session were asked to vote on which side they agreed with. About 57% voted in favor of cannabis use, 14% voted against, and 28% had no opinion.

Eisenberg has received research grants from Rafa Laboratories, Saga Medical Ltd, Israel Pain Association, and Teva Israel. Attal has received support from MSD, Sonofi, Ipsen, Novartis, Aptinyx, Air Liquide, Lilly, and Grunenthal.

Congress of the European Academy of Neurology (EAN) 2020. Presented May 25, 2020.

For more Medscape Neurology news, join us on Facebook and Twitter.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.