Info on nitazenes, also called benzimidazole opioids, a group of potent, synthetic opioids that are increasing in prevalence as the U.S. fentanyl supply is threatened.
There is a sensationalist trap that it's easy to fall into when writing about the War on Drugs from its frontlines.
I've teetered on the edge of it myself when covering fentanyl and xylazine and choosing words such as "unprecedented," "intensifying," "nightmarish," and so on.
The truth is that nothing about humanity's current use of opioids or any other drugs is unprecedented.
In my piece on the evolutionary biology of addiction, I referenced an 1887 newspaper column from the Southern Standard paper of McMinnville, Tennessee. Titled "The Opium Habit - The Most Abject Slavery - Is There Any Emancipation?," the article characterized addicts as "hopeless, helpless slaves, mind weakened, lacking energy for any effort toward recovery, rapidly drifting into imbecility and untimely graves. A peculiar feature is that victims craftily conceal it from their nearest friends..."*
*The same publication advertised a "health-preserving, pure and wholesome" Safe Yeast cure, demonstrating that the natural vs. manmade bias was already established and that the sketchy supplement industry has been around for at least 150 years in the U.S.
This type of language is intimately familiar. It recalls the anti-drug coverage of my youth; the same urgency and moral judgment can be found in the anti-drug exhortations of today.
In popular culture and mass media, drugs are almost invariably associated with the younger generations and societal decline, never mind that our grandparents were high on the same substances and often even wilder ones that have since gone out of fashion.
The fact is that humanity has struggled in our relationship with mind-altering substances for thousands of years - from the time that we discovered alcohol and addictive plant alkaloids such as cocaine and opiates.
During the past 200 years or so, humanity has progressed through at least three major waves of opiate / opioid abuse, and there have been at least three cycles of amphetamine abuse and addiction since these chemicals were first synthesized at the end of the 1800s, as well.
The only thing that is unprecedented about the War on [Certain People Who Use Certain] Drugs is that the government has made it a criminal offense to put select mind-altering chemicals into our bodies. This has resulted in an extinction vortex involving ever more desperate actions on the part of all of the actors involved; it has produced a carceral state in which the United States imprisons more of its citizens per capita than any other country save perhaps North Korea, in which almost 50 percent of incarcerated people are serving time for offenses related to drugs.
As someone who has been addicted to both prescription and illegal drugs, who has lived in the U.S. during the peak crackdown on illicit opioid use and then abroad in a country where legally obtaining benzos and opioids was fairly simple, I can personally testify that, dangerous though these substances are, the majority of the most harmful results of addiction stem from prohibition, not the drugs themselves.
Most of the time, it is prohibition that kills addicts; most of the time, the drugs themselves do not.
The issue with feeding into the hype around what I refer to as the "it chemicals" of the moment - various fentanyl analogues and xylazine, at the present time - is that it removes our current struggles from their proper sociohistorical context.
Less obviously and more importantly, it also establishes a reactive journalistic mode that makes us feel even less well-equipped to face these threats than we really are. It fails to trace the trajectory forward through its next logical steps, which keeps us a step behind in a perpetual game of chemical Whack-a-Mole.
I've already written fairly extensively about what's going on with the fentanyl supply at the moment.
Today, I want to engage in a bit of predictive analysis - to attempt to chart out what's coming in the next phase of the failed War on Drugs, and to talk a little bit about how our government could end this zero-sum struggle against its own citizens.
***
One of the perversities of the War on Drugs is that the more deadly substances are, the more valuable they become.
Doctors use different parameters to evaluate the safety of drugs. One of them is the therapeutic index (TI), defined as the ratio of the highest exposure to a drug that results in no toxicity to the exposure that produces the desired therapeutic effect:
TI = Maximum non-toxic dose / therapeutic dose
The higher the TI, the safer the substance.
In general, doctors would prefer to use less potent chemicals in most situations, particularly with respect to mind-altering chemicals. The first reason for this is that the body reacts less harshly to substances that are milder; side effects, tolerance, and dependence are all less pronounced with less potent substances.
Less potent substances are also easier to formulate and administer. Hence, using morphine, whose active doses are in the range of a few to a couple hundred milligrams (thousandths of a gram) is much safer than using fentanyl, whose active doses can be as low as 50 to 100 micrograms (millionths of a gram).
When using a substance such as fentanyl, lethal doses of which can be as small as a grain of sand, small errors in formulation can mean death. This problem is vastly magnified in the illicit fentanyl supply, which is often synthesized by less-than-expert chemists and then cut and packaged by street-level dealers who don't have the knowledge or the equipment necessary to formulate consistent doses in the appropriate range.
Again, doctors would, generally speaking, prefer to use less potent, less toxic substances.
When the War on Drugs means that addictive substances must be smuggled in through the country's borders, however, the more potent the drug by weight and volume, the easier it is to conceal, and the greater the profit margin on bringing it in.
This is the key reason for fentanyl and its analogues replacing heroin in the U.S. illicit opioid supply.*
*The other reason is that heroin is a semisynthetic chemical produced from opium poppies, whereas fentanyl is a fully synthetic compound that can be synthesized in a lab.
During his first term, Trump pressured China to ban fentanyl export. At the time, China's pharmaceutical companies, mostly centered around the southern city of Guangzhou (Canton, in ancient times), were churning out fentanyl that was shipped to South American cartels, which then trafficked it into the U.S.
China did, in fact, heavily restrict the manufacture and export of fentanyl. However, this didn't put a dent in the U.S. fentanyl supply, as cartel chemists simply imported the precursor chemicals from China, then synthesized the fentanyl themselves.
Let's say that in his second term, Trump's efforts actually disrupt the U.S.' fentanyl supply, unlikely though this is. Will this actually be a win?
The answer is a resounding no, as I will explain below.
***
One of the most alarming elements of the current opioid epidemic is the increase in prevalence of xylazine, a veterinary tranquilizer whose use causes gangrene and other serious medical problems (I wrote about this so-called "tranq dope" here and here). In some parts of the U.S., as much as 40% of the illicit fentanyl supply is now contaminated with xylazine, which is being used to stretch the fent supply and to make the subjective effects of the fentanyl last longer.
Medetomidine, a closely related chemical, has recently appeared in the illicit opioid supply, as well.
These drugs, which aren't approved for use in human beings (despite having been subject to clinical trials after their discovery), are increasing amputation rates and fueling lethal polydrug overdoses that can't be fully reversed with Narcan (naloxone).
Without the fentanyl, the xylazine wouldn't appeal to most drug users, and more importantly, it wouldn't prevent opioid addicts from entering withdrawal. If fentanyl becomes unavailable, then, what's the next opioid of choice?
To answer this question, it's helpful to know something about the Federal Analogue Act (21 U.S.C. § 813), which is a section of the United States Controlled Substances Act of 1986.
The Controlled Substances Act classified substances into different schedules, with Schedule I containing substances with no recognized human medical applications, Schedule II consisting of the most tightly regulated substances with medical purposes in human medicine, and so on through the less-strictly-controlled Schedules IV and V.
These schedules are meant to reflect the medical value of these substances as well as their likelihood of being abused and causing addiction. They profoundly influence how available these substances are by restricting doctors' ability to prescribe the more tightly controlled chemicals.*
*Although this system has many biases, eccentricities, and loopholes, as we saw during the OxyContin epidemic, during which millions of U.S. citizens became addicted to oxycodone, a Schedule II narcotic that should have been subject to intense restrictions.
Okay, back to the Federal Analogue Act, which says that any substance "substantially similar" to a controlled substance listed in Schedule I or II will be treated as though it were listed in Schedule I, meaning that it is illegal to manufacture, sell, and possess for human consumption.
The Act is meant to keep regulators one step ahead in the game of regulatory Whack-a-Mole that I described above. For chemicals such as fentanyl, which has dozens of chemical "cousins" that differ only in the placement and identity of an atom or two, it prevents chemists from making tiny tweaks to the chemical structure in order to create a legal substance that can then be sold for human consumption (until regulators catch up with new legislation banning said tweaked substance).
However, the Act has its limitations. What constitutes "substantial similarity" has been hotly debated as a legal issue. As a result, states often pass emergency legislation to clarify that specific analogues of currently popular recreational substances are illegal whether they are covered by the Federal Analogue Act or not.
Thus, heroin, which is Schedule I in the U.S.*, is out as the illicit opioid of choice, as is fentanyl (Schedule II) and its analogues, which are treated as Schedule I when found in the illicit drug supply and which are the focus of current crackdown efforts.
*A bit of chemical trivia: Heroin is simply diacetyl morphine - a morphine atom with two C-H3-CO groups attached to it, which increase its lipid solubility and hence the rate that it passes through the blood-brain barrier. Heroin is essentially a prodrug for morphine, which means that by the time it hits your brain cells, it has been stripped of its acetyl groups and converted to morphine (as expected, in lab experiments, rats show no discrimination between the two substances). Heroin, called diamorphine, is still used medically in the UK and other countries.
Hydrocodone, hydromorphone, oxymorphone, morphine (and its many analogues), tramadol, meperidine, codeine and its analogues - all previously abused and therefore already controlled.
The thing is, the Analogue Act defines substantial similarity mainly in structural, rather than functional, terms (so, for example, z drugs, which act very similarly to benzodiazepines at the same GABA-A receptor site, were not covered by the Act because they didn't resemble benzos structurally despite their nearly identical mechanism of action).
Because of this, drugs that stimulate the mu-opioid receptor, but which are not structurally similar to opioids that are already federally scheduled, are not covered.
The nitazenes, also known as the benzimidazole opioids after their defining structural motif (see image below), are one such group of synthetic opioids.
I first encountered this group of research chemicals a few weeks ago, when a reader of this blog messaged me to share her story. She's an SEO expert / content creator who, along with her husband, has been on methadone for years.
Both she and her husband regularly order nitazenes from the Dark Web (I have an upcoming piece about some of these "Amazon for drugs" sites, which includes screenshots from sample orders; see image at the end of this section for an example).
Several of these nitazene compounds are available from Dark Web suppliers, and they typically come in the same standardized formulations ordered by universities for biomedical research - marked "Not for Human Consumption" and sometimes with the très chic skull-and-crossbones imagery as well.
The thing about the nitazenes is that many of them are exceptionally potent - so much so that, after their initial synthesis and preliminary clinical explorations in the 1950s, they were declared unfit for use in human beings due to the risk of overdose.
Whereas fentanyl, which has caused an - cough - unprecedented wave of overdoses, is 80 to 100 times stronger than morphine, some of the nitazenes are hundreds to thousands of times more potent than morphine (take etonitazene, for example, which is in fact available from Dark Web suppliers and is 1000-1500 times more potent than morphine, making it at least 10 to 15 times more potent than fentanyl).
What this means is that - without Burroughs-level opioid tolerance - nitazenes are certain to kill you. Even if you have such elevated tolerance, tiny mistakes in the synthetic processes, which can inadvertently generate more potent analogues, or in the process of weighing out individual doses, as well as small variations in your own cardiovascular and neural physiology, can have lethal consequences.
To my knowledge, because of their structural dissimilarity from other licit and illicit opioids, nitazenes will not show up on standard drug screens, providing another incentive for use by people in methadone clinics, drug courts, and other situations where there are punitive consequences for positive drug tests.
Moreover, because they're obtained mainly via the Dark Web, they're shipped in small quantities domestically and internationally, meaning that they won't be affected by any crackdown in conventional drug trafficking through the U.S.-Mexican border.
Nitazenes have the perfect cocktail of traits - potency, selectivity, availability, and undetectability.*
*Some states have passed emergency regulations scheduling specific nitazenes, and there is an emergency Drug Enforcement Agency order from July 2024, which applies until July 2025 unless extended, that temporarily schedules N -desethyl isotonitazene and etonitazepipne. However, because there are dozens of nitazenes to choose from and enforcement is always a step behind legislation, the availability of nitazenes from gray and black market sources is essentially unrestricted at present.
My prediction is that nitazenes are the next "it opioids," and that they will be even worse than fentanyl in terms of their likelihood of causing severe addiction and fatal overdose.
Even the experienced opioid users who have survived oxy, heroin, and now fentanyl and xylazine are likely to be at risk, especially as chronic liver disease, respiratory illnesses, and other consequences of long-term drug use catch up with them.
Because nitazenes have only recently appeared on the public health radar and are not widely tested for, we don't have a handle on how prevalent their use is. However, we do have isolated reports of nitazenes appearing in the illicit drug supply in Florida, Colorado, and other parts of the U.S., in connection with which, unsurprisingly, overdoses have been reported.
***
Things are looking grim, right? They almost seem hopeless, and the way that the mainstream media reports on the War on Drugs reinforces this perception.
This is exactly how we are meant to feel.
Except that things are far from hopeless; the only thing standing between us and liberation from this extinction vortex is ourselves, by which I mean our tolerance for our elected representatives' repugnant failure to do their jobs.
The simple truth is that the vast majority of the United States' current opioid addicts became dependent on highly potent synthetic opioids because of the overprescription of
a high-dose formulation of oxycodone known as OxyContin, which Purdue made billions of dollars by pumping several entire generations full of despite the ample evidence that it was highly addictive, that its time-release mechanism was defective, and that it was being prescribed in hundreds to thousands of times the quantities needed for legitimate pain control purposes.
Although Purdue has been successfully sued, none of its executives have faced criminal prosecution, and the FDA has still not addressed the structural corruption that permitted the situation to arise in the first place.
I mention this context to establish that it was a failure of government regulation that produced the opioid epidemic in the first place. When I was growing up, OxyContin was so popular that I remember kids walking around with turquoise and gold streaks on their shirts from wiping off the extended-release coatings on the 80- and 40-milligram formulations of the drug.
We were stupid, curious kids messing around with stuff from our parents' medicine cabinets, and hundreds of thousands of us are dead because of it.
If you've never witnessed withdrawal from opioids, take my word for this: It is torture just as surely as breaking someone on the wheel or the rack is torture.
Any government that allows its citizens to be poisoned in the interest of Big Pharma profits, then cuts off the supply of the drug that its citizens have become dependent on and addicted to and forces them to become criminals to avoid catastrophic withdrawal, is tyrannous and illegitimate in my eyes. It has become persecutor rather than protector.
It is not too much to ask that opioid addicts who cannot stabilize on the long-acting opioids currently used for maintenance - specifically, methadone and buprenorphine, which have serious drawbacks compared to the shorter-acting opioids that people typically become addicted to and tend to prefer - be granted a safe, legal supply of short-acting opioids for oral or injection use.
The simple fact is that use of these substances should never have been criminalized in the first place. It a violation of bodily autonomy that our Founding Fathers would assuredly have rebuked.
We can contain the problem by removing the demand for illicit opioids, which will also ensure that the next generation of addicts isn't created because the quantity of these substances on the street will exponentially decrease as demand wanes due to the availability of safe, legal alternatives.
To be clear, I'm not advocating the legalization of recreational mind-altering substances, which - absent a suite of carefully weighed co-measures and the right mix of societal conditions - can be disastrous. I'm merely advocating the decriminalization of the possession and consumption of personal-use quantities of these drugs.
***
There is an optimistic historical precedent about what can happen when governments turn away from ineffective, prohibitionist drug policies.
In 2000, when an astronomical one percent of the Portuguese population was addicted to heroin and use of other addictive substances was through the roof, Portuguese leaders gave up: They decriminalized all drugs. Then, they funneled the money that would've been used to prosecute and incarcerate drug users to create programs that reconnected addicts with society, such as microloans for small businesses (in addition to offering residential treatment and other standard medical interventions).
In doing so, they restored addicts' healthy ikigai - the Japanese term for "something to get out of bed for in the morning." They stopped stigmatizing addicts, and they brought marginalized people back into the fold.
Fifteen years later, Portugal's program has been a success by every metric - decreased addiction rates, relapse rates, HIV / Hep B and C infection levels, overdoses, and more.
Things don't have to be this way. They are this way because we hold onto outdated, bigoted, contradictory, and simply incorrect views about addictive drugs and the people who use them. They are this way because we fail to hold our elected leaders responsible for helping us get into this position and then turning on us.
They are this way, in short, because we allow them to be.
There is a sociological theory that holds that the function of social systems is what they are rather than what they are purportedly intended to be. For the U.S. justice system, for example, such a view holds that this system's function - rather than to right wrongs or to contain and rehabilitate dangerous people - is to suppress poor and otherwise marginalized people, to effectively subject them to intergenerational slavery while restricting their political power and keeping them beaten down.
In the case of the War on Drugs, we need to start looking beyond the surface, to consider why our government is so committed to a course of action that has been an abject failure by every conceivable standard.
Why do they want we, the people, to be so distracted, so busy and broke(n) and demoralized by addiction?
What are they so afraid of?
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