Fentalogs: The Next Great Overdose-Reversing Drug Might Already Exist

The overdose crisis is getting worse. Biblical-plague worse. The United States recorded more than 107,000 drug-induced deaths in 2021, up 28 percent from the previous year. Fentanyl has played a key role in this spike, with 64 percent of those deaths involving the synthetic opioid and its analogs. On the ground, harm-reduction groups are working to save lives with medications like naloxone, yet their efforts can only do so much. But they could soon have more tools to save lives: Scientists have discovered several fentanyl-related substances with potential to reverse overdoses. And this month, the US Congress has an opportunity to make studying these drugs and others like them easier.

Right now, getting approved to research fentanyl-related substances (often called “fentalogs” in the lab) requires leaping through onerous regulatory hoops. John Traynor, a pharmacology professor at the University of Michigan, is one of the relatively few researchers who have successfully gone through the approval process, which he calls “not impossible, but frustratingly slow.” It took one year to receive partial approval and another year for his lab to get full access to the fentalogs it needed. In a recent open letter to US president Joe Biden, more than a hundred other researchers called the process “prohibitively difficult.”

The reason for all this red tape? In 2018, the Trump Administration temporarily classified all fentalogs as Schedule I drugs, meaning they have no accepted medical use. (Fentanyl itself remained Schedule II, as it is a commonplace pain medication in hospitals.) The byzantine approval process to study these drugs reflects their status as potential hazards in the eyes of regulators; the US Drug Enforcement Agency (DEA) doesn’t want just anyone getting their hands on these substances, and wants to ensure they are handled properly. Traynor’s lab had to buy a new safe during their approval process, and received many in-person visits from local DEA officers.

This particular classification move was unprecedented. Typically, the DEA schedules individual drugs after a multistep evaluation process, looking at whether each one might have therapeutic value and potential for abuse. This time, it banned an entire group of molecularly related substances without evaluating them first. Thousands of these substances are thought to exist, many of which may be completely harmless, and some of which may be helpful. The ban even covers hypothetical fentalogs—substances that don’t exist yet, and for which there cannot possibly be any proof of danger: like, for instance, substances that could be vital to developing overdose-reversing medications.

Despite this sweeping, unorthodox approach, the Schedule I order was not especially controversial in Washington. In fact, it had bipartisan support. (The Biden administration actually recommended a permanent Schedule I classification for these substances last year.)

This stridency reflects the national mood toward fentanyl. Politicians have been desperate to address the overdoses ravaging their constituencies. (Some have even called for the drug to be labeled a “weapon of mass destruction.”) Prior to the temporary scheduling, drug traffickers had been introducing fentalogs to the streets at a rapid clip; by changing the molecular structure slightly, they had created substances that were harder for law enforcement to detect. The reclassification looked like a straightforward way to stymy traffickers’ efforts. Since Biden took office, this temporary Schedule I policy has been repeatedly extended by Congress. It’s up for renewal once again, as the current extension expires at the end of this year.

Critics say the Schedule I classification is heavy-handed, based on fear rather than evidence. “It bypasses science,” says Maritza Perez, a director at the Drug Policy Alliance, a nonprofit focused on drug policy reform. Frustrated by this blanket ban and eager to develop new overdose treatments, a growing number of scientists, doctors, and other researchers are pushing back.

“A classwide ban based on chemical structure alone would preclude a lot of research that could lead to life-saving medications,” says Gregory Dudley, a chemistry professor at West Virginia University and one of the co-authors of the open letter to Biden. In that letter, Dudley and other scientists argue that permanent Schedule I status could “inadvertently criminalize” important tools to fight the overdose crisis.

Dudley supports a bill introduced last week by US senator Cory Booker (D-New Jersey) called the Temporary Emergency Scheduling and Testing (TEST) Act, which would temporarily extend Schedule I classification again but also require the government to evaluate individual fentalogs, descheduling those with therapeutic uses or without risk of abuse. Booker is hopeful he can pitch his bill as a common-sense approach to the issue. “This bill strikes a middle ground to ensure that we are doing all we can to save lives,” he told WIRED by email.

Even some experts who support permanent scheduling recognize that the status quo doesn’t work. “I believe that the fentanyl-related substances should be permanently put into Schedule I. But I also very strongly believe that the research on Schedule I drugs—and this is more than just the fentanyl-related substances—should be made easier,” says Victor Weedn, a forensic pathologist and professor at George Washington University. In addition to fentalogs, drugs like cannabis and psilocybin are also classified as Schedule I, which has impeded research on those substances as well.

by Kate Knibbs, Wired |  Read more:

Image: Ted Horowitz/Getty Images

[ed. Politicians, DEA, FDA. American drug policy continues to kill more Americans every day (and at a good clip). What's that banal definition of insanity?]