Marijuana-like drugs may offer addiction-free pain relief

Beautiful female backache, close up (Copyright 2008 Marija Savic. All rights reserved.)

As abuse of prescription opioids in the United States has reached epidemic proportions, researchers around the nation have been searching for other ways to offer people pain relief, ways that don't bring such a risk of addiction.

Now, two independent teams of researchers have developed drugs similar to marijuana that show evidence of providing pain relief in laboratory animals, but have no apparent addictive properties and do not cause a "high" that impairs motor function.

The researchers presented their work Nov. 14 at a news conference at the annual meeting of the Society for Neuroscience in San Diego.

Nearly 50 million American adults have significant chronic pain, according to a government-funded study published last year in the Journal of Pain. And opioids — a class of drugs that includes OxyContin, Vicodin and morphine — are commonly prescribed for pain. An estimated 20 percent of patients with pain receive an opioid prescription, a rate that has quadrupled since 1999, according to the Centers for Disease Control and Prevention (CDC).

However, opioids are highly addictive. The CDC estimates that 2 million Americans abused or were dependent on prescription opioids in 2014, contributing to about 14,000 deaths that year (CDC data shows that an equal number of yearly deaths are due to heroin, which is an illegal opioid.)

Researchers in recent years have attempted to create drug compounds that can target pain receptors in the brain but not affect opioid receptors, the source for opioid addiction. Marijuana can provide some pain relief, but the drug has unwanted side effects, such as motor impairment and memory loss, and can be potentially addictive, although it is not an opioid drug.

One research group, led by Andrea Hohmann, a professor of neuroscience at Indiana University, has developed a class of compounds that partially mimics the action of the main psychoactive ingredient in marijuana, THC, short for tetrahydrocannabinol. THC stimulates cannabinoid receptors in the brain to release endocannabinoids, natural pain-relieving molecules.

Hohmann's compounds, called positive allosteric modulators, or PAMs, bind to a recently discovered site on a cannabinoid brain receptor called CB1, but they do not bind to the typical THC receptor or the opioid receptor. As a result, the compound produces pain relief without the high associated with marijuana and without the risk of addiction.

In experiments, the compound provided pain relief to laboratory mice that were given paclitaxel, a common cancer chemotherapy drug known to damage nerves and cause pain.

The PAMs acted in "a very targeted way [and] amplified the therapeutic effect of endocannabinoids," Hohmann told Live Science. "You can view it as 'turning up the gain.'"

Unlike marijuana or prescription opioids, the PAM compounds "do not hit every receptor everywhere," she added.

Another group of researchers, led by Jason Clapper, a scientist at Abide Therapeutics in San Diego, took a different approach and developed a compound that indirectly increased the amount of natural cannabinoids in the brains of rats, which relieved the animals' chronic pain symptoms.

Clapper's compound blocked the body's production of a protein called MGLL, which through a series of events, triggered a release of the brain's natural endocannabinoids, and brought subsequent pain relief.

"Today's findings reveal a better understanding of the body's cannabinoid system and how to modulate it," said Margaret Haney, a drug-abuse expert at Columbia University in New York who was not associated with either research project. "There are now a number of ways to target this system and possibly alleviate pain and other disease without relying on marijuana."

Hohmann noted the path to humans studies "can be a long, slow road" but she's very excited about the potential for this line of therapy.

Originally published on LiveScience.