Frightening spread of synthetic opioids

According to a research letter in the Journal of the American Medical Association, synthetic opioids have eclipsed non-synthetic opioids in terms of opioid deaths. In this 150-Second Analysis, F. Perry Wilson, MD, discusses the new findings and their implications.

What started as the opioid epidemic in the U.S. is rapidly becoming the synthetic opioid epidemic, and we need to begin to grapple with exactly what that means. The issue is brought into stark relief by this research letter appearing in the Journal of the American Medical Association.

Researchers used data from the National Cause of Death File, which records multiple causes of death as reported on death certificates. Over the past 6 years, deaths from opioid overdoses have increased dramatically, and the proportion of those deaths associated with synthetic opioids has increased as well.

Let’s go back to biochem to remember what synthetic opioids are. Your traditional opioids come, essentially, from the poppy plant.

Morphine, codeine, oxycodone, heroin — all of these are poppy derivatives. But in 1960, Paul Janssen (founder of Janssen pharmaceuticals) synthesized fentanyl in a lab. It was approved for medicinal use in 1968.

Fentanyl is markedly more potent than heroin largely due to its lipophilic nature — it can cross the blood-brain-barrier quite easily. Note the difference in the amount of drug sufficient for a fatal overdose:

The combination of high potency and the ability to synthesize the drug without having to grow a field of poppies has quickly led fentanyl to become one of the most smuggled illicit drugs in the world. A 1-kilogram block of fentanyl can fetch as much as $10 million on the black market, compared with a paltry $200,000 per kilogram of heroin.

What the paper shows is that synthetic opioids are increasingly being found in the system of those who overdose on really any drug.

For example, in the year 2010, 4% of patients who died of a cocaine overdose had synthetic opioids in their system. In 2016, that number was up to 40%.

These highly potent drugs, in other words, are adulterating the entire illicit drug chain. And many users have no idea.

I spoke to lead author Dr. Christopher Jones of the Substance Abuse and Mental Health Services Administration about this very issue: “I think what you’re seeing in the data in the last couple of years is that the illicit drug supply has become substantially more dangerous than it has been, and there’s this level of unpredictability and lack of awareness of what are exactly the substances that people are using that are contributing to the overdose risk,” he said.

There are two issues to grapple with here as physicians. First, we need to educate the public as to just how dangerous synthetic opioids are due to their potency. Second, we need to tell people that other recreational drugs — not just opioids — may be cut with these agents. Most people aren’t expecting to overdose on fentanyl when they do cocaine, but it is a real possibility. First responders also need to be trained to recognize opioid overdose even in the absence of a clear opioid ingestion and be equipped with reversal agents like naloxone as well.

F. Perry Wilson, MD, MSCE, is an assistant professor of medicine at the Yale School of Medicine. He is a MedPage Today reviewer, and in addition to his video analyses, he authors a blog, The Methods Man.

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