What are Nitazenes?–More dangerous Than fentaNYL

photorandy2023

6 months ago

I have written or posted several articles on healthcare issues. A series of links has been provided at the bottom of these articles for your convenience.

What Is Nitazene? Side Effects, Risks, and How to Get Help

Nitazenes are exceptionally potent synthetic opioids that have recently emerged as a threat to public health across all continents, from Europe to North America and beyond. Opioids include any drug that acts on opioid receptors in the brain, and any natural or synthetic drugs that are derived from, or related to, the opium poppy.

While the effects of these drugs, colloquially known as Frankenstein opioids, are still being studied, one thing is for sure: nitazenes are even more dangerous—and deadly—than fentanyl. Nitazenes were developed by researchers around 60 years ago as an alternative to morphine, but because of their high potential for overdose were never released.

This article will shed more light on nitazene drugs, covering their origins, potency, side effects, risks, and more.

What Is Nitazene?

How do Nitazenes compare to other opioids in terms of potency:

Nitazene vs. heroin. Certain types of nitazenes can be up to 500 times more potent than heroin.
Nitazene vs. fentanyl. Most nitazenes are tens of times as powerful as fentanyl. For example, etonitazene and its metabolite—N-desethyl etonitazene—are about 10 times stronger than fentanyl, whereas N-pyrrolidino protonitazene is roughly 25 times more potent.
Nitazene vs. morphine. Some nitazenes are upwards of 800 times more potent than morphine.

That said, the potency of nitazenes may vary widely depending on the specific type. While some may be comparable to morphine, others are far more potent than fentanyl, the most potent opioid approved for clinical use.

Nitazenes (benzimidazole-opioids) are a class of extremely potent novel synthetic opioids. First developed in the 1950s by researchers in Switzerland as an opioid analgesic alternative to morphine, nitazenes were never approved for medical use. For many years, nitazenes were not a regular part of the illicit drug market.i With a few isolated exceptions, prior to 2019, nitazenes were primarily known only to researchers studying opioid pharmacology. In fact, the most notable reports of recreational nitazene use prior to 2019 were from 10 deaths in Moscow in 1998ii and an isolated case of personal manufacture in Utah in 2003.

Beginning in 2019, nitazenes emerged more widely on the illicit drug market in Europe. Since then, nitazenes have been identified on nearly every continent, including North America, South America, Asia, and Oceania.iv Due to their recent emergence, comprehensive data on the spread of nitazenes are not available. Limited data described in this report suggest that nitazene use is a growing trend in North America and that availability is likely spreading across the Americas.

As they have emerged across the globe, illicit manufacturers have continuously synthesized new and chemically distinct types of nitazenes.v Today, at least 13 different types of nitazenes have been identified. The most prevalent nitazene is isonitazene (ISO), but other common nitazenes include:

-Metonitazene

-Protonitazene

-Butonitazene

-Etodesnitazene

-Flunitazene

-N-pyrrolidinio etonitazene

Risks and Dangers of Using Nitazenes

The key risks and dangers of using nitazenes include severe adverse effects, opioid dependence and addiction, overdose, and death. Given that not much is currently known about nitazenes, except that they are often found in other illicit drugs, taking them—or buying street drugs—is a gamble that may cost you your life.

Nitazenes are exceptionally potent, which means they may cause severe side effects, such as respiratory depression, at a much lower dose than traditional opioids like hydrocodone.

Their potency also increases the risk of opioid dependence, which is why numerous nitazenes are internationally controlled. In the United States, they generally fall under Schedule I controlled substances because of their high potential for abuse, dependence, and addiction.

Notably, the full scope of the dangers of nitazenes hasn’t been defined yet, as these opioids are new to the public—even though they were developed decades ago.

Nitazenes are highly addictive and continued use can lead to dependency. Although studies about nitazene dependence and withdrawal are limited, nitazene withdrawal has a high potential to be severe and painful. Nitazenes can also cause dizziness, nausea, vomiting, disorientation, loss of consciousness, and seizures. Like other opioids, nitazenes present a high risk of central nervous system or respiratory depression, as well as cardiac arrest.

Nitazenes present an especially high risk for overdose and overdose mortality, due to their high potency. Nitazene potency varies significantly, but all nitazenes are much more potent than natural (non-synthetic) opioids, such as morphine. Table 1 shows that nitazenes range from slightly less potent to many times more potent than fentanyl. Fentanyl itself is generally 25 to 50 times stronger than heroin, which is about twice as strong as morphine. The most common nitazene (ISO) is 250 to 900 times stronger than morphine, while the most potent nitazene is up to 4,300 times stronger than morphine.

Like other opioids, naloxone can reverse a nitazene overdose. However, because of their potency, multiple doses of naloxone may be required to reverse a nitazene overdose.xv Because they are frequently used unintentionally, many people who use nitazenes (and the people around them) may be unaware of the need for multiple naloxone doses — potentially increasing the risk of an overdose becoming fatal.

Effects of nitazenes

Use of any drug can have risks. It’s important to be careful when taking any type of drug.

Nitazenes affect everyone differently, based on:

size, weight and health
whether the person is used to taking it
whether other drugs are taken around the same time
the amount taken
the strength of the drug (varies from batch to batch).

Short term effects of nitazenes include:

euphoria
relaxation, drowsiness and clumsiness
pain relief
reduced stress
itchiness
nausea and vomiting
fever and sweating
slow breathing and heart rate.

Side Effects of Nitazenes

The most common side effects of nitazenes include:

Fever
Nausea
Vomiting
Itchy skin
Sweating
Drowsiness
Slowed breathing
Decreased heart rate

The side effects of nitazenes may range from mild to potentially life-threatening, depending on the amount taken, the potency of the specific nitazene, and other factors. Polydrug abuse, i.e., mixing nitazenes with other drugs, including opioids, may increase the likelihood of severe adverse reactions.

The short- and long-term effects of nitazenes aren’t fully understood yet due to the lack of scientific research. These drugs may cause unexpected side effects, some of which may have lifelong or fatal consequences.

Nonetheless, nitazenes likely expose users to similar risks as other opioids since they work in much the same way despite their structural differences. They bind to opioid receptors, producing analgesic effects and triggering a surge of dopamine, which induces feelings of euphoria and relaxation. Nitazenes tend to have a rapid onset of action, but their effects tend to be short-lived.

Reducing harm

Start with a low dose. Try a small amount first to see how you are affected. It’s important to remember if you are swallowing the drug, it will take longer to take effect than other methods such as injecting. This means there may be more time to get medical help if needed.

Avoid using alone. Have a sober person around who is able to help if needed.

Have naloxone available. Strong opioids like nitazenes may need more than one dose to reverse an overdose.

Avoid taking nitazenes with other substances, in particular other opioids such as heroin. Also avoid depressant drugs like alcohol, GHB, and benzodiazepines.

If you aren’t sure if someone is overdosing, call triple zero and request an ambulance. Do not leave the person alone. Emergency services are there to help and can provide instructions over the phone.

Overdose

If the dose is too high, you might overdose. Call an ambulance straight away by dialling triple zero (000) if you or someone you are with has any of these symptoms:

slow/shallow breathing
bluish/greyish lips and complexion
passing out
coma
death.

Emergency services are there to help and can provide instructions over the phone.

The potency of nitazenes varies between drugs in the class. They can range from levels similar to morphine, to a lot stronger than fentanyl.^6,7

If overdose occurs, naloxone will likely temporarily reverse the drug’s effects, including respiratory depression. More than one dose may be required.⁶

You can easily overdose on nitazenes, and naloxone is the only medication that can save your life in this case. Administering it promptly is of vital importance, as nitazenes may cause respiratory arrest even faster than other opioids. Due to their unmatched potency, a single dose of naloxone may not be enough to reverse a nitazene overdose.

Call 911 immediately if you or someone you know is displaying the signs of a nitazene overdose, such as:

Confusion
Pinpoint pupils
Severe drowsiness
Slowed, shallow breathing
Skin and nail discoloration
Difficulty walking or talking
Loss of consciousness

Ten nitazene-involved deaths were reported in 2020, most of which were attributed to isotonitazene. This number more than quadrupled just a year later; 42 people lost their lives to a nitazene overdose in 2021, mostly caused by metonitazene. All of these deaths involved multiple substances, highlighting the dangers of both nitazene and polysubstance abuse.

As illicit substances, nitazenes are extremely dangerous. Since these drugs are unregulated and their potency and purity may vary widely, there’s no amount you can safely ingest.

Possible long-term effects of nitazenes include:

Tolerance
Opioid dependence
Opioid use disorder (OUD)
Respiratory depression
Opioid overdose
Organ damage
Constipation
Death

Nitazene Dependency vs. Nitazene Addiction

Nitazene dependency and nitazene addiction are among the greatest risks anyone taking benzimidazole opioids is exposed to.

Contrary to popular belief, opioid dependence and opioid addiction aren’t the same; dependence refers to physical reliance on the drug, whereas addiction is predominantly psychological.

Taking nitazenes, especially repeatedly, causes the brain to cease natural endorphin production and create more and more opioid receptors. This leads to tolerance, which is the first sign of nitazene dependency. As tolerance increases, your body will require larger amounts of nitazenes to feel their effects.

Furthermore, people dependent on nitazenes can’t function normally without them, as they experience uncomfortable opioid withdrawal symptoms once these drugs leave their system. This can make quitting nitazenes, and even cutting back on them, virtually impossible.

Nitazene Withdrawal Symptoms

Nitazene withdrawal symptoms occur when people attempt to quit this drug after developing physical dependence. They may be both physical and psychological and resemble severe opioid withdrawal symptoms.

Common nitazene withdrawal symptoms include:

Anxiety
Fainting
Shaking
Cravings
Body aches
Panic attacks
Restless legs
Lightheadedness
Increased sweating
Elevated heart rate and blood pressure
Flu-like symptoms: fever, runny nose, etc.

Given the novelty of nitazenes, there’s limited knowledge about their withdrawal timeline. The onset and duration of withdrawal symptoms may also depend on the specific drug, method of administration, and extent of nitazene use.

Quitting nitazenes “cold turkey” or without medical assistance can be very dangerous due to the risk of health complications, such as extreme dehydration and relapse. Since periods of opioid abstinence reduce tolerance, even your usual dose can be potent enough to cause a potentially fatal overdose.

It’s in your best interest to seek professional opioid addiction treatment to get off nitazenes safely.

Mixing nitazenes and other drugs

The effects of taking nitazenes with other drugs – including over-the-counter or prescribed medications – can be unpredictable and dangerous.

Because of a lack of formal research around mixing nitazenes with other substances, this information covers mixing other substances with opioids in general:

Low risk

Opioids + cannabis: Can work together to increase the effects of both drugs, there is a risk of being more impaired than wanted or planned.

Caution required

Opioids + MDMA/LSD: Unlikely to cause interaction. Don’t use Tramadol and MDMA together due to risk of seizures.

Dangerous

Opioids + nitrous oxide: Can cause impaired coordination, memory loss and passing out.
Opioids + GHB/GBL/benzodiazepines/alcohol: Can cause difficulty breathing, passing out, vomiting and possible death.
Opioids + ketamine: Can cause nausea, vomiting, passing out, and possible death.
Opioids + cocaine/ice/speed: Increases the risk of heart strain. The stimulant effect of cocaine increases heart rate, and the opioid decreases heart rate. Depending on the amount taken there is a risk of respiratory arrest or heart problems if one wears off before the other.

LEGAL STATUS OF NITAZENES

Clonitazene and etonitazene, two of the original nitazenes, are classified as Schedule 1 substances1 under the United Nations 1961 Single Convention on Narcotic Drugs.iv However, this Convention applies only to these two nitazenes – not the larger set of nitazenes that exist today. Many member countries have enacted legislation that further restricts nitazenes, beyond the 1961 Convention. Some countries employ restrictions specific to nitazenes, whereas others use more general opioid control legislation.

In the United States, clonitazene and etonitazene were included in the original Controlled Substances Act of 1971 as Schedule 1 substances. In 2020, the U.S. Drug Enforcement Administration (DEA) classified ISO as Schedule 1, and since then, seven other nitazenes have been similarly scheduled. The United Kingdom also employs specific restrictions to control nitazenes, classifying them as Class A drugs. Canada does not list nitazenes in its controlled substances regulations, but nitazenes are de facto Schedule 1 due to their precursor chemicals. Nitazenes are similarly restricted in Brazil, falling within broader opioid restrictions rather than nitazene-specific laws.

WHY AND HOW DO PEOPLE USE NITAZENES?

People may use nitazenes for the same reasons that they use other opioids, as nitazenes are synthetically engineered to mimic the effects of traditional opioids. Nitazene use may be motivated by self-treatment for physical, mental, or emotional disorders or by a desire to experience opioid effects, such as feelings of euphoria, relaxation, sleepiness, and reduced pain.

Nitazene consumption may also occur unintentionally. Nitazenes are frequently mixed with or counterfeited as other drugs (e.g., heroin, fentanyl, benzodiazepines, or other synthetic drugs) to increase potency and cut costs. Many consumers may be unaware that they are consuming nitazenes, leaving them particularly vulnerable to the risks posed by nitazene use. This unintentional use is also one of the factors making comprehensive data on nitazene use challenging to collect.

Nitazenes are available in many forms, including pills, powders, and sprays – both in “pure” form and mixed with other drugs. Methods of nitazene ingestion include:

-Intravenously

-Intranasally

-Orally

-Sublingually

-Inhalation (vaping)

SCOPE OF USE IN THE AMERICAS

As an emerging substance of concern, we lack a complete picture of nitazene use across the Americas. Data are not currently available from surveys, administrative datasets, or clinical contexts – which are the core sources of drug use information. In the Americas, only the United States, Canada, and Brazil have data related to use, and those data are largely incomplete or proxy measures for actual use. A review of available information from the region did not reveal any data on nitazene use from Central America or the Caribbean.

The United Nations Office on Drugs and Crime (UNODC) Early Warning Advisory (EWA) system suggests that nitazenes are spreading across the Americas and Europe. The UNODC EWA reports that nitazenes were first identified in eight countries in 2019, rising to 19 countries by 2022.v The most frequent reports were (in order) from the United States, Canada, Latvia, Estonia, the United Kingdom, Sweden, and Germany. According to the UNODC EWA, up to February 2024, nitazenes have been reported from Asia, Europe, North America, Oceania, and South America. However, detailed reports are not yet available. While the review of available literature on nitazenes in Latin America found a countryspecific reference only from Brazil, nitazenes might be present in many other countries in the region that have not yet detected or reported them.

For substances with a high risk of overdose, overdoses can be an important proxy measure for use. Though nitazenes pose a high overdose risk, data on nitazene overdoses remain limited because nitazenes are not currently detected by the standard analyses employed by most jurisdictions following overdose events. Two journal publications noted evidence of nitazene overdose deaths globally, but neither could provide detailed estimates of their scope, and both are likely undercounts of the extent of nitazene overdose in the Americas. One study found that nitazenes were involved in at least 200 overdose deaths in Europe and North America from 2020 to 2021. The second found 93 fatalities from 2022 data in eight case reports – primarily from the United States.

PRODUCTION AND TRAFFICKING OF NITAZENES

Because nitazenes are still emerging, very limited information is available on their production and trafficking. A pharmaceutical company in China and its alleged owner were indicted for importing nitazenes into the United States and Mexico, based on unsealed indictments by the U.S. Department of Justice. The European Drugs Agency (EUDA3) also reports that at least some of the ISO sold in Europe was manufactured by chemical companies based in China. However, the extent of these supply chains and their role in the global production of nitazene is currently unknown.

Getting help

If your use of nitazenes is affecting your health, family, relationships, work, school, financial or other life situations, or you’re concerned about someone else, you can find help and support.

Call the National Alcohol and Other Drug Hotline on 1800 250 015 for free and confidential advice, information and counselling about alcohol and other drugs

Help and Support Services search

Find a service in your local area from our list. Simply add your location or postcode and filter by service type to quickly discover help near you.

If you’re looking for other information or support options, send us an email at druginfo@adf.org.au

CONCLUSION

Nitazenes present a new and serious challenge for drug control policy. They are extremely potent and pose major health risks to consumers, including those who unintentionally encounter nitazene-contaminated substances. Meanwhile, illicit manufactures have continued to develop novel forms of nitazenes in the 50+ years since they were first synthesized. Though data remain limited, nitazene use appears to be growing – especially in the United States and Canada. Expanded nitazene surveillance capacity may be required to continue monitoring this emerging concern.

From Fentanyl to Nitazenes: Why the Drug War Keeps Making the Danger Worse

The New York Post recently reported on the tragic deaths, “less than three months apart,” of two Texas friends, ages 21 and 22, who died from overdosing on nitazenes, a type of synthetic opioid more potent than fentanyl. One bought what he thought was Xanax on the underground market, and the other bought what he thought was Percocet (oxycodone plus acetaminophen).

The Post reported that Harris County medical examiners have already seen four cases of nitazene-related overdoses.

Nitazenes can be much more potent than fentanyl and may need several doses of the overdose antidote naloxone to reverse an overdose.

I have been concerned about nitazenes for quite some time. In a 2020 blog post, I asked, “Will Isotonitazene Replace Fentanyl on the Black Market?”:

Reacting to the fact that the synthetic opioid fentanyl and its analogs— largely made and smuggled into the US by labs in China—are responsible for up to 75 percent of opioid-related deaths, the Trump administration persuaded China to impose a ban on the production of fentanyl and its analogs in April 2019. By the fall of 2019, a new synthetic opioid, isotonitazene, made its debut in the US and Canadian black markets. The drug, which is not a derivative of fentanyl but equally as potent, is legal to export from China and is not banned in North America or Europe.

made from a completely different precursor than fentanyl. Piperidine is the precursor for fentanyl, but the precursor for nitazenes is benzimidazole, a compound used to produce various useful medicines such as blood pressure pills, antacids, and antifungal agents. The Swiss drugmaker CIBA, now Novartis, developed the first nitazenes as potential pain relievers in the 1950s but never marketed them.

Writing in USA Today in January 2024, Josh Bloom and I warned:

There are two primary reasons that the emergence of nitazenes in the street drug supply is alarming. One is their extreme potency. An analog called etonitazene may be as much as 1,000-fold more potent than morphine. By comparison, fentanyl is only 100 times more powerful than morphine….

The other reason is that nitazenes are different from fentanyl and its derivatives because researchers fairly well understand the range of the potency of numerous circulating fentanyl derivatives; it is unlikely that any new, unknown derivatives will be more dangerous than those already known and can be identified.

However, researchers know little about nitazene derivatives. Scientists don’t understand how modifications to their chemical structure will affect their potency, making nitazenes the “Wild West” of street drugs.

replacements.”

While the HALT Fentanyl Act did not advance during the 2023–2024 session of Congress, the Senate passed the bill in March of this year, the House passed it in June, and President Trump signed it into law on July 16.

From fentanyl to nitazenes, the pattern is clear: stricter bans don’t eliminate the danger; they just rename it. Unless we change our strategy, more families will experience the heartbreak that those Texas parents are going through now.

Resources

anrclinic.com, “What Is Nitazene? Side Effects, Risks, and How to Get Help.” By Dr. Andre Waismann; http://www.oas.org, “The Emergence of Nitazenes in the Americas.”; adf.org, “What are nitazenes?”; cato.org, “From Fentanyl to Nitazenes: Why the Drug War Keeps Making the Danger Worse.” By Jeffrey A. Singer;