Potent overdose treatment boosts hopes of combating opioid crisis

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Scientists have found a way to boost the effectiveness of the most popular opioid overdose treatment, raising hopes of reducing drug-related deaths that claim tens of thousands of lives every year in the US.

An international research team discovered a chemical compound that improves the potency of naloxone more than seven-fold, potentially allowing the antidote to be given in smaller doses.

Opioid addiction and its lethal consequences have become an intense focus of US politicians and health authorities, with more than 70,000 Americans dying annually for the past several years from overdoses involving the drug. A surge in availability of powerful synthetic opioids such as fentanyl has exacerbated the crisis.

Naloxone is widely known under its brand name Narcan. The naloxone booster discovery, published in Nature on Wednesday, is part of a wider effort to use chemical means to tackle the destructive impact of opioids, said Professor Brian Kobilka, leader of the research.

“This approach will hopefully save lives, but will not address the underlying problem of opioid addiction,” said Kobilka, a joint winner of the 2012 Nobel Prize for chemistry. His laboratory is working on developing non-opioid painkillers, which remove the risk of addiction. US biotech Vertex Pharmaceuticals has a similar drug in late-stage trials.

Kobilka and other scientists from the US, Japan and Denmark screened a library of 4.5bn candidate chemical compounds until they found one called “368” that binds to a specific type of opioid receptor site. The 368 compound amplifies the ability of naloxone to block addictive opioids such as fentanyl and morphine, while minimising withdrawal symptoms.

While Kobilka noted that the latest breakthrough was still in the “very early stages in the drug development process”, it raises the prospect of progress in dealing with the opioid addiction scourge in the US, Canada and other countries.

In a commentary also published in Nature, Catherine Cahill, a researcher at Los Angeles-based Jane & Terry Semel Institute for Neuroscience & Human Behavior, said it was an “important advance, opening up fresh avenues of investigation in the search for solutions to the opioid crisis”.

Naloxone, one of two approved overdose reversal agents, is a key tool used by US health authorities for tackling the opioid epidemic. In California, the state government in April struck a deal with a manufacturer of a generic version to boost availability of free doses of the drugs. Naloxone is available for free in pharmacies in many other states, such as New Jersey and Nevada.

Last year Narcan, which is produced by Emergent BioSolutions, was approved by the Food and Drug Administration for over-the-counter sales. For several years, Emergent stymied efforts to produce an over-the-counter version of Narcan to keep profits high. A two-dose box of Narcan is priced at $44.99.

Emergent, which generated nearly $500mn in sales from Narcan last year, said “this early research appears promising and is important in advancing the science of naloxone to address the opioid crisis”. But it noted the researchers used a subcutaneous dose while Narcan is a nasal spray.

Emergent added that it was “committed to expanding access [while] increasing awareness and maintaining affordability” of Narcan.

Michael Litterer, vice-president at RWJBarnabas Health Institute for Prevention and Recovery, part of New Jersey’s biggest healthcare system, said the biggest impact of a boosted version of naloxone would be as an antidote to “the skyrocketing potency of fentanyl”, he said.

“There’s not enough availability of naloxone in general, let alone enough to combat high-potency fentanyl,” he added.

Emergency services sometimes did not “carry enough Naloxone to save people” when users had taken large doses of fentanyl, said Ryan Hansen, associate professor of pharmacy at Washington university in Seattle, “If these products were co-administered, it could save a lot of lives,” he added.