Scientists have found a way to create drugs you can’t overdose on or become addicted to
The world is facing an opioid crisis.
Countries across the globe are in the clutches of an epidemic and in the US, in particular, there were 63,600 drug overdose deaths last year alone, with about two-thirds linked to synthetic opioids.
Opioids make up a group of drugs best known for effectively treating pain and include the likes of codeine, tramadol, fentanyl, morphine and methadone.
Yet, despite their pain-killing properties, many are associated with a worrying list of side effects ranging from anxiety to severe dependency, hallucinations and even death (as the result of respiratory depression). As a result, doctors typically only prescribe them when other, weaker painkillers are ineffective.
The reason opioids are so dangerous is that they bind to several receptors in the brain. Specifically, they target both the kappa opioid receptor (KOR) and the mu opioid receptor, the latter of which is associated with the most serious effects.
If it was possible to engineer an opioid that only binds with the kappa opioid receptor, and not the mu opioid receptor, it could eliminate these side effects and help bring a safer opioid to market.
Incredibly, that’s what scientists at the University of North Carolina School of Medicine have reportedly done.
“To create better opioids, we need to know the structure of their receptors,” said senior author Dr Bryan Roth from UNC-Chapel Hill. “Until recently, this was impossible. But now we know the structure of the activated kappa opioid receptor. And we showed we can actually use the structure to make a drug-like compound with better properties than current opioids.”
Two postdoctoral fellows in Roth’s lab, first author Tao Che, PhD, and corresponding author Daniel Wacker, PhD, led the work and used a series of experiments to analyse the structure of an activated kappa opioid receptor.
Once they knew the KORs’ structure, the team used computer models to establish which parts of a morphine derivative they could change to make it bind with the receptor more tightly (see above), while ignoring other receptors. After changing the compound, the researchers used lab tests to demonstrate that the new drug would work the same way in practice.
“Now we have a much better understanding of the direction we have to explore in order to create a selective drug to activate only kappa opioid receptors,” Wacker said.
That’s not to say the new opioids solve the problem entirely. Drugs that target KORs have other side effects including hallucinations and dysphoria.
“There is no doubt that drugs which activate kappa receptors cause hallucinations. Salvia divinorum – a hallucinogenic plant – has its effects via kappa receptors,” Roth told Alphr.
When I asked if Roth’s team believes its work could have wider implications on drug manufacturing, he confidently responded: “Yes…it provides a ‘roadmap’ for how one might create drugs to target KOR for improved efficacy and reduced side-effects.”
Image credit: Tao Che and Daniel Wacker, Roth Lab, UNC School of Medicine