Opioid crisis breakthrough: Non-addictive painkiller found effective

Scientists have tested a non-addictive painkiller in primates and found it to be safe and effective. The fact that the compound was successful in a species so closely related to humans strengthens the findings, which could help solve the opioid public health crisis.

The National Institute on Drug Abuse (NIDA) estimate that over 115 people in the United States die from an opioid overdose daily.

The origins of the opioid public health crisis can be traced back to the late 1990s, which was when physicians started prescribing opioid-based pain relievers such as hydrocodone (brand name Vicodin), oxycodone, morphine, codeine, fentanyl, and many others at a higher rate.

According to the NIDA, in 2015, over 33,000 U.S. individuals died from an opioid overdose and another 2 million were living with opioid abuse disorders. Currently, up to 29 percent of those who are prescribed the pain relievers end up abusing them.

The NIDA have also been supporting research efforts to develop alternatives to these highly addictive drugs. One such effort has recently proven successful.

A team of scientists led by Prof. Mei-Chuan Ko, of the Wake Forest Baptist Medical Center in Winston-Salem, NC, developed a non-addictive painkiller called AT-121.

The researchers have just tested the compound in a species of non-human primates called rhesus monkeys and published the results of their experiments in the journal Science Translational Medicine.

'Morphine-like' AT-121 blocks abuse potential

AT-121 was designed with a dual purpose in mind: to block the addictive action of opioids and to relieve chronic pain at the same time.

To this end, Prof. Ko and colleagues developed the drug so that it would simultaneously have an action on the "mu" opioid receptor, which makes opioids effective in relieving pain, and the "nociceptin" receptor, which inhibits the addictive effect of opioids.

Some of the current opioids, such as fentanyl and oxycodone, only act on the mu opioid receptor, which is the main reason that they become addictive and have a wide range of side effects.

Prof. Ko explains, "We developed AT-121 that combines both activities in an appropriate balance in one single molecule, which we think is a better pharmaceutical strategy than to have two drugs to be used in combination."

In their tests, the researchers revealed that the newly designed compound had a "morphine-like" pain-relieving effect, but it only needed the 100th part of a typical morphine dose to achieve this effect.

Importantly, because AT-121 targets both of the aforementioned receptors, it also avoided the side effects that other opioids typically induce, such as "respiratory depression, abuse potential, opioid-induced hyperalgesia, and physical dependence."

As Prof. Ko explains, "Our data show that targeting the nociceptin opioid receptor not only dialed down the addictive and other side effects, it provided effective pain relief."

"[T]his compound," he continues, "also was effective at blocking abuse potential of prescription opioids, much like buprenorphine does for heroin, so we hope it could be used to treat pain and opioid abuse."

He goes on to explain the significance of testing the compound in primates.

"The fact that this data was in nonhuman primates, a closely related species to humans, was also significant because it showed that compounds such as AT-121, have the translational potential to be a viable opioid alternative or replacement for prescription opioids."

Prof. Mei-Chuan Ko

Finally, Prof. Ko lays out the next steps. If more preclinical studies prove that the drug is safe, it will be submitted to the Food and Drug Administration (FDA) for approval, and if they approve it, the drug could be moved into clinical trials in humans.