Key Points

  • Researchers at the National Institute on Drug Abuse have developed a new synthetic opioid called DFNZ that, in rat models, showed reduced signs of addictive behavior compared to morphine.
  • DFNZ is a nitazene, a class of synthetic opioids previously known mainly for fatal overdoses tied to the illicit drug supply.
  • The drug appears to deliver pain relief while sidestepping the dopamine surge and respiratory depression that make traditional opioids dangerous.
  • Findings are preclinical only. DFNZ has not been tested in humans and is not available for medical use.
  • “Less addictive” does not mean non-addictive. Lessons from the OxyContin era suggest caution is warranted as research advances.

Addiction News Weekly Episode 1.2

In This Episode:

00:00 Welcome to Addiction News Weekly by Rehab.com, where we break down the biggest stories in addiction, recovery, and public health.

A New Synthetic Opioid Shows Lower Addiction Potential

00:09 This week, we’re looking at new research into a potential opioid that may be less addictive than current pain medications.

00:25 A new study published by researchers at the National Institute on Drug Abuse suggests that a synthetic opioid may offer pain relief with a lower risk of addiction.1

00:36 Live Science’s reporting on the study notes the compound appears to provide pain relief while producing fewer of the reinforcing effects that are typically associated with addiction.2

00:49 In early testing, the drug showed reduced signs of compulsive use compared to traditional opioids like morphine.

00:56 Researchers say this may be due to how the drug interacts with receptors in the brain,

01:02 potentially separating pain relief from the reward response that can lead to misuse.

01:07 However, the study is still in its early stages, and the findings are based on preclinical data.

01:13 That means the drug has not yet been tested in large human trials, and it is not currently available for clinical use.

01:20 Experts also note that even if a drug is considered less addictive, that does not mean it is non-addictive or without risk.

Expert Analysis with Dr. Sylvie Stacy

01:29 But what does less addictive actually mean in real life? To help break that question down, we asked Rehab.com medical officer Dr. Sylvie Stacy.

01:45 I was both a little skeptical and a little fascinated when I first saw this article and heard about the study that it discusses.

01:55 The study is of a compound that belongs to a class of substances called nitazenes. And these are synthetic opioids that most of us have only been hearing about in the context of fatal overdoses and being laced into the illicit drug supply.

02:12 But this study is on what’s referred to as DFNZ. It really seems to be making some researchers question the idea that a powerful painkiller really has to be a dangerous substance or be addictive.

Dependence vs. Addiction: A Crucial Distinction

02:29 Before I go further into the study and what they found, I do think it’s really important to clarify what is meant by the phrase less addictive, because people very often mix up dependence and addiction.

02:42 So people can of course be physically dependent on a street drug like heroin or fentanyl.

02:49 But dependence can also occur in patients who are using certain prescribed medications exactly according to their doctor’s instructions.

02:57 Dependence means their bodies have adapted to the medication. So if they stop suddenly, they have this fairly predictable and uncomfortable withdrawal syndrome.

03:08 But that doesn’t necessarily mean that they have an addiction.

03:12 Addiction is that compulsive psychological drive to keep using a substance despite it causing significant problems in your life, like financial problems or social, occupational, or legal problems.

How DFNZ Works in the Brain

03:27 So with that in mind, getting back to this article.

03:31 What’s notable about this compound, DFNZ, is that it seems to address both dependence and addiction potential.

03:40 In the rodent models that were studied, the rats didn’t show a typical response that is referred to in the study as the extinction burst. So usually when you stop giving a rat an opioid, it starts to frantically press down on a lever to try to get some more. But the DFNZ rats just stopped. They didn’t seem to have that very hijacked reward response that drives the transition from regular routine use of a substance to a full-blown substance use disorder.

04:12 And the pharmacology here is pretty clever too. DFNZ uses a mechanism that involves a glycoprotein, which you can think of as kind of like a bouncer at the blood-brain barrier.

04:25 DFNZ gets into the system to help with pain, but this bouncer kicks the drug out of the brain almost as soon as it gets in. And because the drug can’t stay in the brain’s respiratory centers, it doesn’t slow or stop the drive to breathe, which is how opioids usually end up killing people.

04:44 It also avoids a specific receptor complex of opioid receptors and another receptor called the galanin receptor.

04:54 We think these pairings of receptors are the primary triggers for that massive dopamine spike when someone uses opioids. And that’s the feeling of being high that makes a drug so reinforcing.

05:07 And by bypassing that spike, you can potentially provide significant pain relief without the euphoric reward that leads to drug misuse.

Lessons from the OxyContin Era

05:19 So the study discussed in this article is an excellent showcase of this concept, but we have to remember, of course, that a rodent’s brain and a human’s brain are not the same thing.

05:30 Many listeners probably remember being told in the past that certain opioids are safe and not addictive.

05:38 And we know how that story ended back in the nineties and the early 2000s. But that said, I remain quite optimistic given the results of this study. I hope that DFNZ moves on to human trials.

05:52 If it does though, our medical protocols and our understanding of patient monitoring are going to have to evolve to some extent to make sure we’re monitoring the right variables and factors that give us all the information we need about both pain control and physical dependence and addiction potential.

Conclusion

06:19 And that concludes this week’s focus. For more, visit Rehab.com. We’ll be back next week.

Sources in This Episode

Nahas K. New pain-relief opioid could be much less addictive than morphine, rodent study finds. Live Science. Published April 18, 2026. Accessed April 28, 2026. https://www.livescience.com/health/medicine-drugs/new-pain-relief-opioid-could-be-much-less-addictive-than-morphine-rodent-study-finds

Gomez JL, Ventriglia EN, Frangos ZJ, et al. A µ-opioid receptor superagonist analgesic with minimal adverse effects. Nature. Published April 1, 2026. Accessed April 28, 2026. https://doi.org/10.1038/s41586-026-10299-9

Dr. Sylvie Stacy
By Dr. Sylvie Stacy
Published on April 28, 2026