Two Scripps Florida scientists won a five-year, $3.7 million grant from the National Institutes of Health to develop safer pain medications, the Jupiter nonprofit said Wednesday.
Laura Bohn and Thomas Bannister will use the money to study new compounds that separate the powerful pain relief of opioids from the drugs’ life-threatening side effects of decreased breathing rate and lower blood-oxygen levels.
The scientists also will look into other downsides of opioids, including addiction risk and constipation.
The scientists are trying to find a way to treat pain without the side effect of overdose and without the risk of addiction -- the Holy Grail of pain treatment. Bannister acknowledged that safer pain pills will address only one part of the opioid epidemic.
“It’s a multi-faceted crisis,” Bannister said. “I wouldn’t ever sell this as a way out of the opioid crisis.”
Bohn and Bannister have been working on safer painkillers since 2011.
“It wasn’t really thought of as a crisis at that point,” Bannister said. “Heroin hadn’t really reemerged as a street drug, and we hadn’t seen the overdoses from drugs laced with fentanyl. Those things have really turned the heat up.”
Last year, Bohn and Bannister published a paper in the journal Cell describing compounds that activate the body’s mu opioid receptor, which relieves pain, without likewise activating the betaarrestin pathway, which is associated with the harmful effects of pain killers.
“The core idea of this is that when the opioid binds to the receptor, there are two pathways -- one for pain relief, another for breathing,” Bannister said.
Opioid painkillers and related drugs, such as heroin, sedate users and slow their breathing. At high doses, and when mixed with alcohol or other sedatives, users can die in their sleep when the body's breathing mechanisms cease functioning.
Bohn and Bannister are developing a drug known by the mundane moniker SR-17018. Bohn and Bannister first focused on how to treat pain without slowing breathing. Measuring the effects on lab mice was a straightforward matter of gauging oxygen levels in their blood.
“The respiration part was relatively easy,” Bannister said. “Addiction is quite a bit more complicated. We don’t know as much about addictive properties and constipation and tolerance.”
Even constipation, which sounds like a side issue in a deadly crisis, is a costly side effect for the health system. In some cases, physicians won’t release patients from the hospital until they’ve resumed normal bowel movements.
But it was the surge in overdose deaths that last year led President Donald Trump to declare a national emergency.
Prescription pills often introduce patients to opioids, and for some the pain medications turn into an addiction that leads to the abuse of legal opioids and illegal drugs such as heroin and black-market fentanyl. In Florida in 2016, more than 15 people a day died of opioid-related overdoses.
Doctors use opioids to treat severe pain after accidents and surgeries. While different patients respond differently to the drugs, patients who take them for long periods build up tolerance and, in some cases, addiction.
Today's opioid epidemic is partly the fallout from pharmaceutical companies' efforts, starting in the mid-1990s, to market the painkillers as safe.
Palm Beach County remains the epicenter, leading all counties in heroin-related overdose fatalities with 571 lives claimed in 2016.
Despite promising progress so far, Bohn and Bannister stress that SR-17018 won't be available at pharmacies anytime soon. The next step is a series of trials to study safety and side effects, first in animals and then later in people.
“It’s a long way before it really gets validated in people,” Bannister said.
Researchers note that the human brain is complicated, and how it works remains in many ways a mystery, so inventing an addiction-proof, overdose-free painkiller is a monumental task.