On a warm night three summers ago, Kai Raydon, a student at the University of Colorado, Boulder, opened a package of orange-white powder that he had purchased through an encrypted site on the dark web. He had ordered quaaludes, an illegal sedative, but wasn’t taking chances. He placed a sample on a fentanyl test strip: negative.
Mr. Raydon weighed out a gram using a digital scale that sat on the coffee table in his room at his fraternity. Grateful Dead posters decorated the walls. Delilah, his rat terrier, sat with him on the couch. With a rolled-up $50 peso bill, he inhaled the gram.
“Just tried the ludes and they are just as good as people say,” he messaged a friend on social media. “Holy Hell. Doses are $20.”
His girlfriend, Emma Buck, had been in the hallway on a call. She returned to find Mr. Raydon pacing — an odd reaction, “uncharacteristic of a sedative,” she said.
It wasn’t a sedative. It was something new and unknown — and part of an explosion of novel lab-made chemicals that is redefining the illicit drug market. In recent years, hundreds of ultra-potent drugs have emerged, often identified by health authorities and law enforcement only after they have shown up in the toxicology report of someone who has overdosed.
Most of these substances originate in traditional medical research, in scientific papers and patents that were published by legitimate scientists and companies and then copied and modified by illicit chemists. This is the science-to-street pipeline and it has come to dominate the illicit drug market.
In his fraternity room that night, July 22, 2023, Mr. Raydon started to feel sick. He took a cold shower, put on an anti-nausea bracelet and lay with his head on Ms. Buck’s lap. The pair had fallen hard for each other that spring. He was a neuropharmacology major, fascinated by the brain. “He was the most intellectually curious person I’d ever met,” she said.
She left after midnight; by then, she said, he was feeling better and had fallen asleep. The next day, when she couldn’t reach him, she came to check on him. She found him in bed, with Delilah perched on him. She thought he was asleep until she felt his cold body.
Katie Becker, a morgue supervisor for Boulder County, assisted in the autopsy. She noticed foam around his lips: a telltale sign of overdose, typically associated with fentanyl. The drug slows breathing and suppresses the gag reflex, causing fluid to build up in the air sacs, effectively drowning the user.
But a toxicology exam found no fentanyl. “There was nothing in the report that would explain the cause of death,” Ms. Becker said. “It was a mystery.”
The story of what happened to Mr. Raydon, and the detective story that followed, is a chilling example of the intimate relationship between well-intended science and the creators of the world’s most lethal drugs. By its end, the case would lead its scientific investigators unsettlingly close to their own doorstep.
A synthetic frontier
In 1971, President Richard Nixon began what became known as the war on drugs; that year, 6,771 Americans died of overdose. In 2024, 80,000 did, an increase of nearly 70 percent from just a decade earlier.
What has changed are the drugs. In the 1970s, the main targets — coca, poppies, marijuana — came from farms. Today, most illegal drugs are made in unregulated labs around the globe, from big enterprises in China and India to single-person operations run from anonymous apartments.
The drugs include fentanyl, but it is just one of hundreds of synthetic, ever more potent compounds known as novel psychoactive substances. The United Nations Office on Drugs and Crime now lists 1,446 new psychoactive substances, up from 643 a decade ago.
Experts refer to this trend as the “digitization of drugs.” Today, with the internet, virtually any esoteric molecular structure or chemistry study that is published online is instantly available to armchair chemists and illicit drug suppliers the world over.
Dr. Laura Bohn, an associate dean of research at the Morsani College of Medicine at the University of South Florida who develops new opiate molecules for medical research, described the internet as the “cookbook” for the drug trade, offering “thousands of papers, proceedings and books with different molecules.”
It has also made the drug supply dangerously unpredictable. Compounds are now mixed, substituted and adulterated almost continuously. A recent study from the National Institute of Standards and Technology, or NIST, which tests illicit drugs from around the country, found that 42 percent of samples that contain fentanyl include five or more psychoactive compounds, up from 23 percent three years ago. The supply is so reliably polluted that even careful users like Mr. Raydon are operating blind.
“You have almost no chance of knowing what you’ve got,” said Edward Sisco, a research chemist at NIST.
For scientists, the new reality is all too clear: The best-intentioned research discovery, if published, could quickly give rise to the next deadly street drug.
“We had no idea these compounds would be used illicitly,” said Alexandros Makriyannis, a professor of medicinal chemistry at Northeastern University in Boston and director of the Center for Drug Discovery there. “It didn’t occur to us.”
There are countless examples. In 2001, Dr. Makriyannis published his discovery of AM-2201, a lab-made molecule that mimicked properties of cannabis but with greater potency. The patent for AM-2201 — a chemical name taken from Dr. Makryiannis’s initials — suggested that it might be used to develop a drug to treat “pain, glaucoma, epilepsy, nausea, AIDS wasting, multiple sclerosis” and other potential ailments.
A pain drug never materialized, but within several years, illicit drug makers had copied and manipulated AM-2201 to create the basis for an illegal, addictive and sometimes deadly synthetic compound called Spice.
As novel drugs continued to emerge, well-intentioned scientists tried a new tactic to get ahead of the problem: They would try to predict what deadly drugs might emerge next. This is what drug experts call “prophetic” research. But as scientists are discovering, illicit drug makers can pirate this literature, too.
The rise of nitazenes
On Oct. 19 of 2023 three months after Mr. Raydon’s death, samples of his blood and urine arrived for analysis at the Center for Forensic Science Research & Education, a nonprofit forensics laboratory in Horsham, Pa., outside Philadelphia. The laboratory is tasked with identifying a rapidly growing assortment of new synthetic drugs that are further polluting the drug supply and causing widespread overdoses.
In 2023, Mr. Raydon’s was one of 268 cases of unidentified novel drug substances handled by the Center for Forensic Science Research & Education; this year it is on pace to exceed 1,000. The center is run by Alex J. Krotulski, a forensic toxicologist and rising expert on novel psychoactive substances. Stocky and quick to smile, Dr. Krotulski fuels his day with energy drinks and coffee spiked with Splenda. Colorful sculptures of skulls decorate his office, and paintings of skulls hang on the walls. “It’s because I deal with death so much,” he said, sitting at his desk one afternoon in the summer of 2024.
When Mr. Raydon’s samples arrived, they were run through a high-resolution mass spectrometer, which finely measures the molecular weights of compounds as a first step toward identifying them. The compounds were then compared against a database of 1,200 known drug molecules — several times more molecules than a typical medical examiner can access. By November, the lab had found a match for the molecule that had killed Mr. Raydon: N-desethyl etonitazene.
“It is 10 times more potent than fentanyl,” Dr. Krotulski wrote in an email to Ms. Becker, the Boulder pathologist. “We are just seeing this for the first time.”
By “first time,” Dr. Krotulski meant that they were seeing the compound on the streets for the first time. But he realized that he had encountered it previously, in a paper written by a colleague not two years earlier.
N-desethyl etonitazene, the drug found in Mr. Raydon, belongs to a family of synthetic opiates called nitazenes. This chemical group first caught Dr. Krotulski’s attention in the spring of 2019, when he and other scientists on the leading edge of forensic toxicology learned about a fatality in Alberta, Canada. The cause was a nitazene variant called isotonitazene. The same drug also showed up in deaths in the coming months in Minnesota, Iowa and Illinois, among other places.
These drugs appeared to be following a familiar pattern from lab to street. The nitazene drug family was developed in the late 1950s by a Swiss pharmaceutical company, Ciba, whose scientists hoped they had found a new pain drug. But in early experiments, nitazenes dangerously suppressed breathing. So, like many pharmaceutical creations with unacceptable side effects, nitazenes all but disappeared, and the chemical structures and effects were hardly known beyond old German patents.
Dr. Krotulski and his peers had a theory about why nitazenes were suddenly resurfacing in the drug supply: The U.S. and China had outlawed fentanyl, and illicit drugmakers had gone looking for a replacement.
“Every time something happened to one compound, something new would come to take its place,” Dr. Krotulski said.
Then, in July of 2020, a second nitazene, called metonitazene, showed up in a death in Ohio. The prospect that nitazenes were morphing was no longer theoretical. “Oh, no,” Dr. Krotulski recalled thinking at the time. “This is really happening.”
‘Why do we wait?’
By this time, Dr. Krotulski had begun brainstorming with a small group of molecule detectives, which included academic researchers, officials in Europe and forensic toxicologists at commercial companies. Could they reasonably predict what nitazene might appear next on the streets? By modeling the future, could they help police officials and hospitals to prepare, and even save lives?
“Why do we wait until a 15-year-old kid dies or until somebody overdoses?” said Roy Gerona, a forensic toxicologist at the University of California, San Francisco, who helps identify new drug compounds for the Drug Enforcement Administration and works independently of Dr. Krotulski’s group.
Christophe Stove, a toxicologist at the University of Ghent in Belgium, argued that this predictive work could help shorten the life span of dangerous new drugs by getting them declared illegal more quickly and perhaps discouraging their production.
“We are telling the drug producers, ‘We already know about this compound, we already have the standards, it’s already detectable,’” he said. “We’d rather have the data before a compound is on the mass market.”
Among the influential prophetic scientists is István Ujváry, a Hungarian medicinal and pharmaceutical chemist who worked in agricultural pesticides in Hungary for decades before becoming obsessed 20 years ago with the rise of new synthetic drugs.
The shelves of his home office in Budapest are packed with scientific journals, historical proceedings from conferences and esoteric small-run chemistry books with such titles as “Opiates and Characteristics and Functions of Opioids” and “Europsycho Pharmacology.” Dr. Ujváry scours these for compounds that could become threats.
“I look at a patent,” he said. “It could be 200 pages or 400 pages, with 50 to 200 individual compounds described. I look for the most active ones in the table and I print it out, highlight, extract the two or five most active ones, look at the structures and I present them at conferences.”
In 2020, shortly after the first nitazenes appeared, officials from the European Union Drugs Agency, which tracks the emergence of new molecules, asked Dr. Ujváry to help them write an in-depth paper exploring which nitazene substances might appear next. A top European authority sent an email to Dr. Ujváry asking him to “provide a top-level review” on “some of the other new opioids we have seen (or may see).”
Dr. Ujváry was aware that such predictions came with a risk: Street chemists could lift that research and use it to make a drug. The prophecy could spur the reality.
It had happened before. In April 2013, Samuel Banister, an accomplished medicinal chemist and expert in the rise of novel psychoactive substances, had published a paper in the journal ACS Chemical Neuroscience profiling a recently detected synthetic cannabinoid called AB-001 and several related molecules. He used his initials as codes for several of these, including two molecules: SDB-006 and 5F-SDB-006. Several months later, customs agents in Finland seized drugs based on these molecules in a shipment from Hong Kong.
“Someone somewhere in the world had read our paper and replicated our work,” Dr. Banister said. He was “scared and concerned” at the time, he recalled. “It’s when I started wondering: What is the responsibility of scientists in all of this?”
The circle tightens
In March of 2021, the brainstorming and predictive work on nitazenes was published in two independent but related papers in the ACS Chemical Neuroscience, a journal of the American Chemical Society. The articles would later haunt Dr. Krotulski as he reviewed Mr. Raydon’s toxicology report.
The first paper, by Dr. Ujváry and several top officials with the European Union Drugs Agency, reviewed research dating back to the 1950s to consider various nitazene variants and ways that the molecules could be modified to create new ones that were more or less potent. In the paper, the authors argued that much of this information had already been published; if underground chemists were mining the literature, they already knew what Dr. Ujváry and his colleagues had to say.
Indeed, by this time, even newer nitazenes had begun appearing. In February of 2021, protonitazene, which is 15 times more potent than fentanyl, surfaced in Iowa, and has since killed at least 200 people. Still another variant, which was 40 times more potent than fentanyl, surfaced in March 2021 in West Virginia and has killed at least 100 people.
The second paper in 2021, written by other scholars, including Dr. Stove from the University of Ghent, looked at existing nitazene compounds, modeled hypothetical new ones and explored how they interact with the opioid receptor in the brain.
Not long after, some of the drugs mentioned in the two papers appeared on the street for the first time. In November 2022, N-desethyl isotinizonaze surfaced in a drug sample from Florida; it is 80 times more potent than fentanyl and has been detected in at least 40 fatal overdoses, Dr. Krotulski said.
Then, in October 2023, another one emerged. It had been one of the hypothetical compounds mentioned in the second paper, and was called N-desethyl etonitazene. But now it had been made real: It was the drug that killed Mr. Raydon.
Unlike many new illicit drugs, this one could not have been directly pirated from older scientist literature; the original German patent had not discussed its potency and structure. That appeared to come with the 2021 prophetic paper, which, Mr. Krotulski said, put the compound on the map.
Confronting the past
Had the papers contributed in some way to the death of Mr. Raydon? Were forensic toxicologists predicting the future, or were they creating it? In November of 2024, at a symposium in Philadelphia, Simon Elliott, a visiting professor in forensic toxicology at King’s College London, put the question directly to Dr. Ujváry, Dr. Krotulski and Dr. Stove.
“Is there a chance,” Dr. Elliott asked, “with chicken and egg, when you are proposing certain compounds, that illicit chemists saw these and said, ‘You’ve done the hard work for us, we now know the chemistry?’” He continued: “Is there a chance you actually start the trend?”
The symposium, organized by Dr. Krotulski’s lab, had brought together officials from the U.S. Drug Enforcement Administration and U.S. Customs and Border Control as well as scientists from around the world. Over three days of presentations and panel discussions, they wrestled with where new molecules were coming from (mostly scientific literature and patents), who was making them (labs in India, China and Mexico) and how best to stop the spread (more chemists and resources).
Dr. Krotulski was first to respond to Dr. Elliott’s question.
“The reality is, yes, there’s always a possibility,” he said. Case by case, it was typically unclear where clandestine chemists found their ideas, he added. “Nobody knows what’s really coming next,” he continued. “So you can make the argument that having that information is more beneficial to us than not having the information.”
Dr. Ujváry followed. “If I can access the literature,” then “they also can find those structures,” he said. The challenge, he added, was to be “not one step behind but one step ahead.”
Dr. Stove agreed. “If we can think of it, others can think of it,” he said. “We’re not that smart.” In a more recent interview, Dr. Stove said he didn’t know if the paper had played a role in the emergence of N-desethyl etonitazene. “I’m not entirely sure it would not have surfaced,” he said, adding that the drug might have emerged anyway.
In the audience in Philadelphia was Ms. Becker, the morgue supervisor who had assisted in the autopsy on Mr. Raydon; Dr. Krotulski had invited her to present the case and the discovery of N-desethyl etonitazene in his system. Later, she said she found it interesting that the effort to predict new nitazenes might have played a role in seeding them. But she appreciated the effort to stop the spread.
“We’re all trying to stay ahead of it,” she said.
Matt Richtel is a health and science reporter for The Times, based in Boulder, Colo.
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