prescription painkillers
Addiction & Substance Overuse

A Safe Painkiller?

Researchers working from scratch have developed a new opioid drug candidate that blocks pain without the dangerous side effects of current prescription painkillers.

The international team — led by scientists at UC San Francisco, Stanford University, the University of North Carolina (UNC), and the Friedrich-Alexander University Erlangen-Nürnberg in Germany — explored more than four trillion chemical interactions in the study.

The findings, published in the journal Nature, showed how researchers used the newly deciphered atomic structure of the brain’s “morphine receptor” to custom-engineer a novel drug candidate that blocked pain as effectively as morphine in mouse experiments, but did not share the potentially deadly side effects typical of opioid drugs.

In particular, the new drug did not interfere with breathing — the main cause of death in overdoses of prescription painkillers as well as street narcotics like heroin — or cause constipation, another common opioid side effect. The new drug also appears to side-step the brain’s dopamine-driven addiction circuitry and did not cause drug-seeking behavior in mice.

More work is needed to establish that the newly formulated compound is truly non-addictive and to confirm that it is as safe and effective in humans as it is in rodents, the authors say. But if the findings are borne out, they could transform the fight against the ongoing epidemic of prescription painkiller addiction.

Deaths from opioid drug overdoses have been on the rise in the US for decades. According to the Centers for Disease Control and Prevention, 28,000 Americans died of narcotic overdoses in 2014, four times more than in 1999, with more than half of these deaths involving prescription drugs. The epidemic has gotten the attention of national leaders: in February, 2016, President Obama proposed $1.1 billion in new funding for opioid addiction treatment, and in July Congress passed the Comprehensive Addiction and Recovery Act, a bill intended to curb opioid abuse and improve treatment.

But as damaging as opioids can be, modern medicine depends on these drugs as our most powerful weapon against pain.

“Morphine transformed medicine,” said Brian Shoichet, PhD, a professor of pharmaceutical chemistry in UCSF’s School of Pharmacy and co-senior author on the paper. “There are so many medical procedures we can do now because we know we can control the pain afterwards. But it’s obviously dangerous too. People have been searching for a safer replacement for standard opioids for decades.”

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