Cannabinoid drugs have a head start in the search for opioid alternatives

But new, safer opioids are nipping at their heels.

Cannabis-based drugs are slowly finding foothold in the pharmaceutical industry. The FDA has approved some synthetic cannabinoids to treat nausea from chemotherapy, and weight loss in AIDS patients. But even as the opioid epidemic highlights the need for new kinds of painkillers, cannabinoids’ potential to relieve pain remains largely untapped. Still, a handful of pharmaceutical companies are developing cannabinoid pain treatments, despite regulatory hurdles.

“We’re very interested in finding a new therapeutic for pain, because we have so few options out there,” explains Ziva Cooper, an associate professor of clinical neurobiology at Columbia University Medical Center. Cannabinoids are emerging as a candidate, particularly for sufferers of chronic pain.

Cannabinoids aren’t the only new approach to pain relief, but they are one of the most promising. New opioid compounds, designed to relieve pain without adverse effects like dependency, have also shown potential. “Opioids are super powerful analgesics,” explains Cooper, who expects the new opioid compounds could provide greater pain relief than cannabinoids. But research into these novel opioids is still in its infancy, and they haven’t yet been studied in humans. Meanwhile, there is a growing body of clinical evidence that cannabis and synthetic cannabinoids can reduce symptoms in chronic pain patients—and companies have started developing drugs to harness this effect.

Researchers and companies face regulatory hurdles

“Legal and regulatory restraints on cannabis research remain a tremendous obstacle, especially in the United States,” says neurologist and psychopharmacology researcher Ethan Russo. Having spent the bulk of his career in the United States, Russo is now Director of Research and Development at the International Cannabis and Cannabinoids Institute, a research center in the Czech Republic. “I’m afraid that real progress will continue to occur only abroad,” he says.

Russo, a former scientific advisor to GW Pharmaceuticals, believes non-synthetic cannabis extracts hold particular potential for developing alternatives to opioids. But many companies are focusing their efforts on synthetic cannabinoids. “These would provide clear intellectual property to their patent holders, as compared to cannabis itself,” says Russo. But there are also other reasons for companies to focus on synthetics. For one, they’re less regulated, and thus easier to research.

Established drug shows potential for pain relief

GW Pharmaceuticals is a drug company in the UK that specializes in cannabinoid drug development, and one of the few to focus on plant-derived cannabinoids. Their drug Sativex, while not approved in the United States, is used in 30 other countries to treat spasticity associated with multiple sclerosis. The company believes Sativex has potential to treat pain as well. Based on early trials in the mid-2000s, Sativex received conditional approval in Canada for cancer pain and nerve pain from multiple sclerosis. More recently, it was approved to treat these types of pain in Israel too.

However, recent clinical trials have had limited success, and more evidence of the drug’s effectiveness against pain is needed. “Whilst certain trials have been successful, not all of them have met their endpoint,” said Geoffrey Guy, chairman and founder of GW Pharmaceuticals. “There will be more work required to determine the optimal patient population in which to study cannabinoids in pain.”

GW Phamaceuticals

A pain relief patch

Zynerba Pharmaceuticals, a US company, also focuses exclusively on cannabinoid-based therapies. One of two drugs currently in development is ZYN001, a skin patch to relieve pain by delivering synthetic THC.

The drug is for patients suffering from nerve pain and fibromyalgia, chronic widespread pain that can’t be adequately treated with standard medications, including opioids. “Although opioids are often used as a treatment of fibromyalgia, the effectiveness is limited due to a reduced availability of opioid receptors associated with the condition,” explained Kim Lawson, a pharmacologist specializing in the syndrome.

Lawson says other synthetic cannabinoid drugs—nabilone and dronabinol—have been shown to significantly reduce pain and improve quality of life for people with fibromyalgia. However, they also have adverse effects, like dizziness and nausea, which have led many patients to drop out of clinical trials. As a patch, ZYN001 can be absorbed gradually to avoid the THC spikes associated with oral drugs. The drug would also bypass the liver, which Zynerba hopes will facilitate a lower dose, making the drug easier to tolerate.

An opioid developer enters the cannabinoid game

Another US company, Cara Therapeutics, specializes in new kinds of opioids that target different opioid receptors than traditional pain drugs like morphine. They’re also pursuing a cannabinoid-based treatment: the compound CR701, which is in preclinical development. Though it’s not yet been tested in humans, the company says CR701 has been shown to relieve pain resulting from nerve damage in animals.

Experts are cautious, but optimistic

The types of pain targeted by these three drugs represent just some of the many conditions for which opioids are prescribed. “It seems to be clear that cannabinoids are more effective for chronic pain, whereas they’re not effective for acute pain,” says Cooper. “If you’re going in for a dental procedure, cannabinoids aren’t the way to go.”

Much is still unknown about potential adverse effects of cannabinoid pain medication. “There’s definitely cognitive impact of cannabinoids and cannabis,” says Cooper, who lists memory issues, anxiety, paranoia, and nausea among potential side effects. There’s also the potential for abuse. While abuse liability has yet to be comprehensively studied on people using cannabinoids exclusively for medical purposes, a recent WHO assessment reported that CBD, one of the two cannabinoids in Sativex, was not associated with abuse potential. With variations in dose and type, comparing cannabinoids' side effects to those of opioids can be like comparing apples and oranges. “But in the greater scheme of things,” says Cooper, “the overall adverse clinical impact of cannabis and cannabinoids is considerably less than opioids.”

Russo too is optimistic about cannabinoids’ potential. “They portend to offer relief to millions of patients for whom conventional medicines have failed,” he says. “With 64,000 people dying each year of opioid overdoses in the United States, it is incumbent upon politicians and regulators to realize that cannabis is far less dangerous than opioids, and is part of the solution.”

Featured image courtesy of GW Pharmaceuticals.