Chemists Likely Found A Way To Make Opioids Less Addictive

Chemists may have found a way to make opioids less addictive: adding a fluorine atom to the drug’s structure. The change keeps the opioid weak in normal body tissue but active at the inflamed site of an injury. So it can still ease pain while carrying less addiction risk.

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Summary: Opioid addiction is a major health threat. But not all opioids are equally addictive. So changing the chemical structure of current opioids may make them less addictive. Researchers think they have found a way. Adding a fluorine atom to various opioids seems to make them less addictive while still working well at the site of injury.

The opioid epidemic shows no sign of fading. But we cannot deny that opioids are among the best painkillers. So giving up opioids completely may cause problems. Doctors may find it hard to manage moderate to severe pain without them. Life for people with chronic pain may become miserable.

It has also long been known that opioids differ a lot, and some are not addictive at all. For example, codeine, used for pain and dry cough, is unlikely to cause addiction. The diarrhea drug loperamide does not cause addiction at all. Even the lab-made opioid painkiller tramadol does not seem to cause addiction. So why not try to create strong opioid painkillers with no addictive effect?

Current opioids need small changes so they stop crossing the blood-brain barrier and causing a high. This is possible, though hard. But with overdoses and painkiller abuse rising, it is also urgently needed. In many medical conditions, opioids are almost impossible to replace.

Of course, chemists would have done this long ago if it were that simple. Still, recent years have brought many advances in technology. For example, computer-based chemistry has given chemists more power.

How do opioids work in the body?

There are many types of opioids, but they share some basic structures. Small differences between them lead to very different chemical and even biological properties.

One problem is that big changes to an opioid’s structure can make it work less well. But to cut the addictive effects of opioids, we need ways to make bigger changes while keeping the painkilling effect.

This topic is not new. Some opioids already have a very different chemical structure from morphine and other classic opioids. One example is fentanyl.

Studies show that opioids work in part by becoming positively charged when they touch body fluids.

This positive charge helps opioids lock onto their target. The problem with current opioids is that they become charged in all body fluids, in every organ, including the brain. So if we could stop that, or make them charge only at certain sites, it could help prevent addiction and many side effects of opioids.

How can an opioid be made less addictive?

Researchers think the opioid structure must change so the drug becomes charged only in very acidic places. Studies show injured or inflamed tissue is more acidic than other body parts, because lactic acid builds up there. So any opioid that needs more acid to switch on will work more at the target site. It will also be less likely to cause a high.

Researchers found this is possible, mainly by adding a fluorine (F) atom near the nitrogen in fentanyl’s amine group. That keeps fentanyl less active in ordinary body fluids. It becomes more active at sites of inflammation and pain. What is exciting is that new studies show adding the fluorine atom to morphine may also change how it acts. Morphine will then need a bit more acid to switch on. That would make morphine more active in injured tissue and less active in the brain and elsewhere. So it would be less likely to cause addiction.

Today, opioid treatment programs have started using suboxone, another possible medicine. Researchers think they can explore ways to change how oxycodone and hydrocodone work too. But so far, this approach has only been tested in labs, where it seems to work. Now it needs to be tested in clinical trials.

Frequently asked questions

Is there a new painkiller to replace opioids?

Chemists are building a smarter opioid, not a replacement. Adding a fluorine atom near the nitrogen in fentanyl’s amine group keeps the drug less active in ordinary body fluids. It becomes more active in the acidic tissue around an injury or inflammation, where lactic acid builds up. The same change to morphine makes it need more acid to switch on. So it acts on injured tissue and less in the brain.

Why are opioids addictive?

Opioids work by becoming positively charged in body fluids, which lets them lock onto their targets. Today’s opioids take on that charge everywhere, including the brain. Reaching the brain across the blood-brain barrier is what causes the high. An opioid that becomes charged only in the more acidic setting of injured or inflamed tissue would keep its pain relief. It would also be less likely to cause addiction.

When will less addictive opioids be available?

Not until they pass clinical trials. So far the fluorine approach has been tested only in labs, where it seems to work. Researchers want to extend it to oxycodone and hydrocodone. The work took this long because big changes to an opioid’s structure can weaken its pain relief. Recent advances such as computer-based chemistry have given chemists more power to make those changes safely.