About 72,000 Americans died of a drug overdose in 2017, and at least two thirds of those deaths were opioid related. The opioid crisis has been driven by overprescription of opioid painkillers over the past 30 years. Opioid manufacturers convinced doctors that pain was being undertreated and that opioid medications were non-addictive and safe for long-term use. While it is true that pain is a serious issue and needs to be treated seriously, many people received excessive opioid prescriptions, and many of those people developed a dependence on opioids when they normally would not have been at risk.
As the scope of the crisis came to light, doctors started curtailing their opioid prescriptions. Following the release of CDC guidelines in 2012, opioid prescriptions continued to fall and there has been considerable improvement on that front. However, pain remains a problem for many people. One priority in fighting the opioid epidemic has been to develop less addictive pain medication so fewer people become dependent while taking pain medication following injuries and medical procedures. There may recently have been a breakthrough in finding a safer pain medication.
A new drug called AT-121 may offer pain relief without the addictive potential of opioids. A recent study tested the drug in 15 adult rhesus monkeys and found the pain relief was similar to morphine at about one percent of the dose. Not only that, but the monkeys didn’t become addicted to the drug. When they were allowed to self-administer AT-121 by pressing a button, they chose not to. The drug doesn’t appear to have the same euphoric effects that make opioid drugs so addictive. Perhaps most importantly, AT-121 doesn’t appear to suppress breathing the way opioids can. Typically, when someone dies of an opioid overdose, their respiration is suppressed until they suffocate, but that doesn’t appear to be a danger with this new drug. If these effects transfer to humans, it could be a major breakthrough in safer pain relief.
The drug works by acting as an agonist at both the mu-opioid receptor and the nociceptin receptor. The interaction with the nociceptin receptor appears to block the side effects of opioids that are related to dependence. Most opioid drugs only target the mu-opioid receptor. This relieves pain, but it also causes euphoria. The monkeys in the study chose to continue dosing themselves with oxycodone, but not AT-121. When animals that were dependent on oxycodone were given AT-121, it actually reduced their signs of addiction. In addition to reducing dependence and respiratory suppression, targeting both the mu and nociceptin receptors makes the drug a more effective pain reliever.
AT-121 is not ready for the market yet. It still has to pass human trials, but if it lives up to its early promise, it could make a big difference in the number of people who become addicted to opioids every year.
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