Although President Trump has so far stopped short of declaring opioid dependency a national emergency, he is expected to deem it a public health emergency, freeing up funds that states will be able to use to address the crisis. The move comes amid alarming reports of overdoses and deaths from prescription painkillers. In 2015 alone, more than 15,000 deaths were blamed on overdoses of commonly prescribed opioids, according to the U.S. Department of Health and Human Services.
As public health officials work to address the problem, scientists are laboring to develop opioid alternatives that can relieve pain without causing dependency and other adverse side effects. This week a team at Indiana University reported promising results in mice for a novel compound that enhances the brain’s natural ability to produce painkillers.
The compound is part of a class of medicines called positive allosteric modulators (PAMs) which work by precisely targeting receptors in the body that amplify natural processes rather than turning them on or off altogether. The PAM used in this study pumps up the production of two pain-relieving brain chemicals, anandamide and 2-arachidonoylglycerol, according to a press release from the university. These compounds act on a brain receptor called CB1—the very same receptor that responds to THC, the main ingredient in cannabis.
In mice, the PAM enhanced the pain-relieving power of anandamide and 2-arachidonoylglycerol without causing effects associated with marijuana, like impaired motor function, the researchers found. The compound also didn’t produce the tolerance that commonly leads to dependence. They reported their results in the journal Biological Psychiatry.
The researchers believe the key to the PAM’s effectiveness is that it cues the body’s natural painkillers to hit a limited number of targets at the right time, rather than flooding many receptors throughout the body. “If these effects could be replicated in people, it would be a major step forward in the search for new, non-addictive forms of pain relief," said study coordinator Andrea G. Hohmann, a neuroscience professor at IU Bloomington, in the statement.
Several companies are working on opioid alternatives, including Trevena, Mebias and Nektar Therapeutics. They have all been focusing on proving in clinical trials that their drugs produce opioid-like pain relief without raising the risk of dependency and other adverse effects.
The PAM used in the study led by Indiana University, called GAT211, was developed at Northeastern University. During the study, the scientists compared GAT211 to two other alternative pain relievers and found that it was most likely to maintain its effectiveness over time and less likely to create addiction, they reported.