According to the CDC, from 2000 to 2014 nearly 500,000 people died of drug overdoses in the U.S. 2014 had a record high of 47,055 deaths, with opioids being involved in 61 percent of fatalities. Although the majority of opioid overdoses were caused by heroin, a growing number of addicts start with prescriptions (morphine, Oxycontin, fentanyl) and eventually switch over to less expensive street heroin. In a panel discussion last March, President Barack Obama said the opioid crisis is one of the largest problems facing the country. “When you look at the staggering statistics in terms of lives lost, productivity impacted, cost to communities, but most importantly cost to families from this epidemic, it has to be something that is right up there at the top of our radar screen.” With no relief in sight for this epidemic, researchers have found hope in a new opioid that may be able to deliver pain relief with none of the addictive qualities.
The research began in 2000 when Dr. Laura Bohn learned about a protein called beta-arrestin. Beta-arrestin attaches to opioid receptors when activated by an opiate such as morphine or Oxycontin. Bohn began experimenting on mice that were unable to produce the beta-arrestin protein, and what she found was astonishing. Mice that lack the protein and are given morphine felt numb to pain, but didn’t suffer the negative side effects. They didn’t get high, build up tolerance, go through withdrawals, or experience irregular breathing—a symptom which kills many addicts.
Bohn’s research also revealed the mu-opioid receptor to be more complex than originally believed. Previously, scientists thought it was a simple switch that can be turned on or off. “The hope is you’d have another molecule that looks like morphine and binds to the same receptor, but the way it turns the receptor on is slightly different,” says Dr. Aashish Manglik, an opioid receptor researcher at Stanford University. This discovery inspired researchers to begin searching for a compound that could attach to opioid receptors, while avoiding the negative side effects associated with beta-arrestin.
Researchers screened nearly three million compounds using virtual simulations before discovering a drug that produced the perfect interaction with the mu-opioid receptor: PZM21. Tests on lab mice showed the compound to reduce pain without any breathing interference and they didn’t appear to get high. “If you give a mouse a drug that activates its reward pathways like cocaine, amphetamine or morphine, the mice just run around more,” Manglik says. “In this compound, we saw very little of that.”
Although early research looks promising, the drug has a long road before it can be approved for use in humans. “[Opioids have been used] medicinally and recreationally for more than 4,000 years because of its remarkable pain-relieving and euphoria-inducing properties,” Professor Brigitte Kieffer, of McGill University in Canada, says. She believes that PZM21 as “a step towards this perfect drug.” This drug would not only help people manage debilitating pain more effectively, but it would also help to alleviate the scourge of opioid addiction that is now killing more Americans each year than traffic accidents.