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Nitazenes

1d ago 13:50

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This week we talk about OxyContin, opium, and the British East India Company.

We also discuss isotonitazene, fentanyl, and Perdue.

Recommended Book: The Thinking Machine by Stephen Witt

Transcript

Opioids have been used as painkillers by humans since at least the Neolithic period; there’s evidence that people living in the Iberian and Italian Peninsulas kept opium poppy seeds with them, and there’s even more evidence that the Ancient Greeks were big fans of opium, using it to treat pain and as a sleep aid.

Opium was the only available opioid for most of human history, and it was almost always considered to be a net-positive, despite its downsides. It was incorporated into a mixture called laudanum, which was a blend of opium and alcohol, in the 17th century, and that helped it spread globally as Europeans spread globally, though it was also in use locally, elsewhere, especially in regions where the opium poppy grew naturally.

In India, for instance, opium was grown and often used for its painkilling properties, but when the British East India Company took over, they decided to double-down on the substance as a product they could monopolize and grow into a globe-spanning enterprise.

They went to great lengths to expand production and prevent the rise of potential competitors, in India and elsewhere, and they created new markets for opium in China by forcing the product onto Chinese markets, initially via smuggling, and then eventually, after fighting a series of wars focused on whether or not the British should be allowed to sell opium on the Chinese market, the British defeated the Chinese. And among other severely unbalanced new treaties, including the ceding of the Kowloon peninsula to the British as part of Hong Kong, which they controlled as a trading port, and the legalization of Christians coming into the country, proselytizing, and owning property, the Chinese were forced to accept the opium trade. This led to generations of addicts, even more so than before, when opium was available only illicitly, and it became a major bone of contention between the two countries, and informed China’s relationship with the world in general, especially other Europeans and the US, moving forward.

A little bit later, in the early 1800s, a German pharmacist was able to isolate a substance called morphine from opium. He published a paper on this process in 1817, and in addition to this being the first alkaloid, the first organic compound of this kind to be isolated from a medicinal plant, which was a milestone in the development of modern drug discovery, it also marked the arrival of a new seeming wonder drug, that could ease pain, but also help control cold-related symptoms like coughing and gut issues, like diarrhea. Like many such substances back in the day, it was also often used to treat women who were demonstrating ‘nervous character,’ which was code for ‘behaving in ways men didn’t like or understand.’

Initially, it was thought that, unlike with opium, morphine wasn’t addictive. And this thinking was premised on the novel application method often used for morphine, the hypermedia needle, which arrived a half-century after that early 1800s isolation of morphine from opium, but which became a major driver of the new drug’s success and utility. Such drugs, derived scientifically rather than just processing a plant, could be administered at specific, controllable doses. So surely, it was thought, this would alleviate those pesky addictive symptoms that many people experienced when using opioids in a more natural, less science-y way.

That, of course, turned out not to be the case. But it didn’t stop the progression of this drug type, and the further development of more derivations of it, including powerful synthetic opioids, which first hit the scene in the mid-20th century.

What I’d like to talk about today is the recent wave of opioid addictions, especially but not exclusively in the US, and the newest concern in this space, which is massively more powerful than anything that’s come before.

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As I mentioned, there have been surges in opioid use, latent and externally forced, throughout modern human history.

The Chinese saw an intense wave of opioid addiction after the British forced opium onto their markets, to the point that there was a commonly held belief that the British were trying to overthrow and enslave the Chinese by weighing them down with so many addicts who were incapable of doing much of anything; which, while not backed by the documentation we have from the era—it seems like they were just chasing profits—is not impossible, given what the Brits were up to around the world at that point in history.

That said, there was a huge influx in opioid use in the late-1980s, when a US-based company called Purdue Pharma began producing and pushing a time-released opioid medication, which really hit the big-time in 1995, when they released a version of the drug called OxyContin.

OxyContin flooded the market, in part because it promised to help prevent addiction and accidental overdose, and in part because Purdue was just really, really good at marketing it; among other questionable and outright illegal things it did as part of that marketing push, it gave kickbacks to doctors who prescribed it, and some doctors did so, a lot, even when patients didn’t need it, or were clearly becoming addicted.

By the early 2000s, Purdue, and the Sackler family that owned the company, was spending hundreds of millions of dollars a year to push this drug, and they were making billions a year in sales.

Eventually the nature of Purdue’s efforts came to light, there were a bunch of trials and other legal hearings, some investigative journalists exposed Purdue’s foreknowledge of their drug’s flaws, and there was a big government investigation and some major lawsuits that caused the collapse of the company in 2019—though they rebranded in 2021, becoming Knoa Pharma.

All of which is interesting because much like the forced legalization of opium on Chinese markets led to their opioid crisis a long time ago, the arrival of this incredibly, artificially popular drug on the US market led to the US’s opioid crisis.

The current bogeyman in the world of opioids—and I say current because this is a fast-moving space, with new, increasingly powerful or in some cases just a lot cheaper drugs arriving on the scene all the time—is fentanyl, which is a synthetic opioid that’s about 30-50 times more potent than heroin, and about 100 times as potent as morphine. It has been traditionally used in the treatment of cancer patients and as a sedative, and because of how powerful it is, a very small amount serves to achieve the desired, painkilling effect.

But just like other opioids, its administration can lead to addiction, people who use it can become dependent and need more and more of it to get the same effects, and people who have too much of it can experience adverse effects, including, eventually, death.

This drug has been in use since the 1960s, but illicit use of fentanyl began back in the mid-1970s, initially as its own thing, but eventually to be mixed in with other drugs, like heroin, especially low-quality versions of those drugs, because a very small amount of fentanyl can have an incredibly large and potent effect, making those other drugs seem higher quality than they are.

That utility is also this drug’s major issue, though: it’s so potent that a small amount of it can kill, and even people with high opioid tolerances can see those tolerances pushed up and up and up until they eventually take a too-large, killing dose.

There have been numerous efforts to control the flow of fentanyl into the US, and beginning in the mid-20-teens, there were high-profile seizures of the illicitly produced stuff around the country. As of mid-2025, China seems to be the primary source of most illicit fentanyl around the world, the drug precursor produced in China, shipped to Mexico where it’s finalized and made ready for market, and then smuggled into the US.

There have been efforts to shut down this supply chain, including recent tariffs put on Chinese goods, ostensibly, in part at least, to get China to handle those precursor suppliers.

Even if that effort eventually bears fruit, though, India seems to have recently become an alternative source of those precursors for Mexican drug cartels, and for several years they’ve been creating new markets for their output in other countries, like Nigeria, Indonesia, and the Netherlands, as well.

Amidst all that, a new synthetic drug, which is 40-times as potent as fentanyl, is starting to arrive in the US, Europe, and Australia, and has already been blamed for thousands of deaths—and it’s thought that that number might be a significant undercount, because of how difficult it can be to attribute cause with these sorts of drugs.

Nitazenes were originally synthesized back in the 1950s in Austria, and they were never sold as painkillers because they were known, from the get-go, to be too addictive, and to have a bad tradeoff ratio: a little bit of benefit, but a high likelihood of respiratory depression, which is a common cause of death for opioid addicts, or those who accidentally overdose on an opioid.

One nitazene, called isotonitazene, first showed up on US drug enforcement agency radars back in 2019, when a shipment was intercepted in the Midwest. Other agencies noted the same across the US and Europe in subsequent years, and this class of drugs has now become widespread in these areas, and in Australia.

It’s thought that nitazenes might be seeing a surge in popularity with illicit drugmakers because their potency can be amped up so far, way, way higher than even fentanyl, and because their effects are similar in many ways to heroin.

They can also use them they way they use fentanyl, a tiny bit blended into lower-quality versions of other drugs, like cocaine, which can save money while also getting their customers, who may not know what they’re buying, hooked, faster. For context, a fifth of a grain of nitazene salt can be enough to kill a person, so it doesn’t take much, less than that, if they want to keep their customers alive, to achieve the high they’re looking for. A little bit goes a long, long way.

This class of drugs is also difficult to detect, which might be part of the appeal for drug makers, right now. Tests that detect morphine, heroin, and fentanyl do not detect natazines, and the precursors for this type of drug, and the drugs themselves, are less likely to be closely watched, or even legally controlled at the levels of more popular opioids, which is also likely appealing to groups looking to get around existing clampdown efforts.

Right now, drug agencies are in the process of updating their enforcement and detection infrastructure, and word is slowly getting out about nitazenes and the risk they potentially pose. But it took years for sluggish government agencies to start working on the issue of fentanyl, which still hasn’t been handled, so it’s anyone’s guess as to when and if the influx of nitazenes will be addressed on scale.

Show Notes

https://www.wired.com/story/a-new-type-of-opioid-is-killing-people-in-the-us-europe-and-australia/

https://link.springer.com/article/10.1007/BF02161116

https://www.thelancet.com/journals/lanpub/article/PIIS2468-2667(24)00024-0/fulltext

https://www.theguardian.com/society/2025/nov/03/nitazenes-synthetic-opioid-drug-500-times-stronger-than-heroin-fatal

https://www.nature.com/articles/d41586-025-03280-5

https://theconversation.com/10-times-stronger-than-fentanyl-nitazenes-are-the-latest-deadly-development-in-the-synthetic-opioid-crisis-265882

https://www.cato.org/blog/fentanyl-nitazenes-why-drug-war-keeps-making-danger-worse

https://www.cfr.org/backgrounder/fentanyl-and-us-opioid-epidemic

https://en.wikipedia.org/wiki/Purdue_Pharma

https://en.wikipedia.org/wiki/Oxycodone

https://en.wikipedia.org/wiki/Fentanyl

https://en.wikipedia.org/wiki/Nitazenes

https://en.wikipedia.org/wiki/Opioid

https://en.wikipedia.org/wiki/Timeline_of_the_opioid_epidemic

https://en.wikipedia.org/wiki/Opioid_epidemic

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Nitazenes

Let's Know Things

published 1d ago