Fentanyl regulations in the US are so strict they could interfere with lifesaving research

According to chemist Gregory Dudley, as the number of opioid-related deaths continues to rise in the US, researchers are prohibited from studying the very substances that could be an antidote to overdose.

When Covid-19 broke out, the US and many other countries poured huge resources into research, developing antivirals, vaccines, and other treatments to save lives immediately. This general mobilization contrasts sharply with another major public health crisis that is still shaking the country: the drug overdose epidemic.

In 2021, more than 100,000 people overdosed in the United States, nearly double the number in 2018. Most of these deaths were related to opioids. But rather than responding to this crisis with an all-out push for more effective life-saving measures, policy has been designed to stifle research and curtail critical innovation. This leaves our society trying to fight this crisis with one hand tied behind its back.

The synthetic opioid fentanyl is one of the substances behind the overdose epidemic. It is 50-100 times stronger than morphine and highly addictive. An overdose of fentanyl can be fatal. In addition, an alarming amount of unregulated fentanyl is sold illegally in the US. This is without a doubt a serious problem and a serious cause for concern.

But this is also the case when fentanyl is approved by the US Food and Drug Administration for use in surgery and for the treatment of severe and chronic pain, including in people with cancer. The World Health Organization has identified fentanyl as an essential drug. It is not always easy to draw the line between a life-saving drug and a dangerous drug.

In the US, the Drug Enforcement Administration classifies drugs into five different categories, or “schedules,” based on their medical value and potential for abuse. The lower the number, the more strictly the substance is regulated and the more severe the punishment for illegal use or sale. Schedule I is reserved for drugs that do not have a safe, accepted medical use and have a high potential for abuse. Research on Schedule I drugs is severely limited.

Fentanyl itself is a Schedule II drug. In 2018, the Trump administration classified all “fentanyl-related substances” as Schedule I drugs, suggesting that they all have a high potential for abuse (and are not used for medical purposes). Since then, Congress has expanded this Schedule I classification several times while retaining the original assumptions.

The problem is that compounds chemically related to fentanyl can be more or less dangerous, more or less potent, or even counteract its action; they can serve as an antidote for fentanyl overdose. The naive assumption at the heart of this 2018 decision subjected countless substances – both real and hypothetical – to the harshest drug penalties and effectively made it impossible for scientists to work with or study them.

The purpose of all this may be to deter the development of illicit drugs, but the implications are broader and more complex. The only defining characteristic of a “fentanyl-related substance” is its molecular structure, not its function, activity, or potential for abuse. Structure is important, but functionality is more important here.

Consider naloxone, an opioid antagonist or antidote that can reverse an overdose. In Tennessee alone, from October 2017 to June 2022, naloxone was used to prevent an estimated 50,000 deaths. Naloxone has a molecular structure related to morphine; it is a product of research related to morphine.

Could fentanyl research lead to new and possibly more effective life-saving interventions? We won’t know until we’ve done the work, but there are already encouraging signs. The US National Institute on Drug Abuse studied a small handful of fentanyl-related substances and found that at least one (we don’t know which) exhibited naloxone-like antagonist properties. We should follow suit, but research to develop more effective fentanyl-related drugs is currently halted.

Meanwhile, trafficking in fentanyl variants continues unabated, and cases of opioid overdose continue to rise.

Last year, I joined over 100 other scientists to send a letter to the Biden administration calling for changes that would make overdose drug development easier, not harder. In October of this year, New Jersey Senator Cory Booker introduced the Testing Act, which calls into question the assumptions underlying the classification of all “fentanyl-related substances” into the Schedule I drug list. As written, the Testing Act extends the temporary a list of fentanyl-related substances for two years, but also requires the government to test more of these substances, report the results, and remove anything that does not belong to Schedule I. This is a common sense approach with broad support.

We must treat the US overdose epidemic as an urgent public health crisis. The time has come to untie the hands of scientists and let them fight this with all their might.

Gregory Dudley professor of chemistry and department head at West Virginia University.