Since the onset of the opioid crisis, scientists have been looking for safe, effective, non-addictive alternatives to pain management. Not only do many people misuse their prescription opioids, but a lot of people who end up taking harder drugs started out with an opioid painkiller. According to data from 2002 to 2012, people who reported having used prescription opioids improperly were 19 times more likely to begin using heroin. Now, researchers from the Wake Forest Baptist Medical Center in Winston-Salem, North Carolina have developed a non-addictive painkiller called AT-121.
It might sound like a droid from Star Wars, but AT-121is an opioid compound that, according to a study published in Science Translational Medicine in August, provides better pain relief than even morphine. At the same time, it works without the euphoric effects that cause people to keep seeking drugs and lead to dependency and addiction.
Opioids work by attaching to certain receptors in the brain, called mu-opioid receptors, that are associated with pain. There are opioids naturally present in the body, which send signals to the brain to block pain, slow down breathing, and cause a general feeling of calmness and wellbeing. Unfortunately, those natural opioids can’t be produced in numbers large enough to deal with severe or chronic pain. Opioid medications mimic the effects of the natural ones, essentially tricking the receptors and allowing the drugs to activate the pain-moderating nerve cells in the brain. They don’t work quite the same as the real thing, however, and they end up causing abnormal messages to be sent through the reward system, essentially overstimulating it. This teaches the brain to keep seeking out opioids to get that feeling of reward.
The answer to the opioid problem, then, seems to be developing a drug that eases pain without triggering the pleasure centers in the brain. AT-121 targets those same pain receptors as existing opioids, but it also binds to a second set of receptors, called the nociceptin opioid receptors, which are proteins that regulate behaviors related to emotions and instincts. Blocking both types of receptors at once seems to keep the drug from triggering a pleasure response while still effectively treating the pain.
The researchers from Wake Forest tested AT-121 on rhesus monkeys and discovered that a similar degree of pain relief could be obtained at a dose 100 times smaller than morphine. The monkeys were able to self-administer the drug, but they showed no indications of doing so repeatedly or unnecessarily. They also didn’t exhibit any of the side effects that are usually present in humans who take morphine, such as itching and problems breathing.
The drug is still many years away from being considered for approval in humans, but it does at least open up a new avenue for research. Scientists are currently studying several other compounds that selectively target receptors to prevent addiction.
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