Warning of new opiod drug (nitazene) on the streets: Question re strength...

[sbrothy]

Whenever these opiods are mentioned they usually mention that e.g. fentanyl is "50 times stronger than heroin" and "100 times stronger than morphine". Now it's nitazene which the public is told is everything from "much stronger than heroin" and "200 times stronger than fentany"!

Do these numbers make sense at all? How do they arrive at them? Kill thousands of mice?

En passant: nitazene have already been found in both Oxycontin pills and in street "heroin" here, so Naloxone is more important than ever.

EDIT: maybe this question belongs in Biology and Medical....

 

[.Scott]

The basis of the comparison is equivalent dosage. So much smaller doses of nitrazenes are required to cause similar effects.
Given the uncontrolled nature of it manufacturing and handling, the potential for accidental and lethal overdose is much higher - even among bystanders or law enforcement.
Worse yet, nitazenes are a class of chemicals - all are very potent synthetic opioids but some are much more potent that others. So no good comparison can be made without knowing which nitazene.

They are responsive to naloxone, but additional naloxone doses may be required.

 

[sbrothy]

Thank you. I was pretty sure it was simplified, but I guess the point is to make it sound scary. Mission accomplished in that case. Cutting the nitazene (or fentanyl as the case might be) up and selling it as "heroin" would make much more sense than putting a deadly dose in a pill, so I'm puzzled as to the motive (if anything) of these psychopaths. Killing your users doesn't seem to me to make much sense.

EDIT: Corrected some broken language which meant the opposite of what I was trying to convey.

 

[Laroxe]

The problem here is like Scott says one of manufacture and supply, Nitazenes are not used clinically so people simply get no indication of the dose contained in what they buy, this is also the case with Fentanyl, most overdoses are from illegally produced and supplied drugs. With these synthetic opiates the production tends to be cheaper and easier, but when carried out illegally there is no quality control, the dose is often a lottery. The production process can lead to various similar compounds that are still active but have less predictable effects, It's also likely that the production equipment is also used for other drugs so cross contamination appears to be common. However, the potency of these drugs means that exposure during the production process makes it, and any enforcement actions by police, much more risky.
Most of the overdoses seen, appear to be accidental and death is usually as a result of respiratory depression. Making the antidote drug Naloxone more widely available can reduce the number of deaths but because of the legal status of these drugs interventions that try to make drug use safer often face opposition. As more of these synthetic compounds become available, the risks, increase, and often include first time experimental users.

 

[sbrothy]

The problem here is like Scott says one of manufacture and supply, Nitazenes are not used clinically so people simply get no indication of the dose contained in what they buy, this is also the case with Fentanyl, most overdoses are from illegally produced and supplied drugs. With these synthetic opiates the production tends to be cheaper and easier, but when carried out illegally there is no quality control, the dose is often a lottery. The production process can lead to various similar compounds that are still active but have less predictable effects, It's also likely that the production equipment is also used for other drugs so cross contamination appears to be common. However, the potency of these drugs means that exposure during the production process makes it, and any enforcement actions by police, much more risky.
Most of the overdoses seen, appear to be accidental and death is usually as a result of respiratory depression. Making the antidote drug Naloxone more widely available can reduce the number of deaths but because of the legal status of these drugs interventions that try to make drug use safer often face opposition. As more of these synthetic compounds become available, the risks, increase, and often include first time experimental users.

Indeed. I have test kits which will reveal respectively fentanyl and nitrazene which I hand out as I pass through town. I've had feedback that the street "heroin" is "contaminated" with both. So bringing Naloxone around with me has never been more important.

Unfortunately, saving a junkie's life using Naloxone will get you no thanks (go figure). Quite the contrary actually. Luckily we're told to call the ambulance also. They're better equipped with handling the fury when an addict wakes up after having been blue in the head and clinically dead, and blaming you for destroying their "wonderful" feeling of oblivion.

 

[berkeman]

So much smaller doses of nitrazenes are required to cause similar effects.

Is that because the same dose of nitrazines can bind to more opiod receptors, or some other effect?

They are responsive to naloxone, but additional naloxone doses may be required.

Do you have a link that discusses why this is true? I carry naloxone on-duty for my EMS shifts, but currently only 2 doses...

 

[.Scott]

First, I need to say I am less than happy about Googles use of AI. Before AI, it was much easier to find references. With AI, I often get more information than I can verify - and that is certainly the case in this instance.
My strategy with Google AI is to take some of the terms used in the AI response and include them in my follow-on searches - to see if I can't get better non-AI sources. On the topics related to nitazenes, there have consistently been substantial claims made by the Google AI with no good non-AI sources.
That said, a good search term is "nitazene mu-opioid receptor".

Is that because the same dose of nitazenes can bind to more opioid receptors, or some other effect?

This NIH page: describes a study and provides this summary:

Synthetic opioids are increasingly challenging to combat the opioid epidemic and act primarily at opioid receptors, chiefly the G protein-coupled receptor (GPCR) μ-opioid receptor (MOR), which signals through G protein-dependent and β-arrestin pathways. Using a bioluminescence resonance energy transfer (BRET) system, we investigate GPCR-signaling profiles by synthetic nitazenes, which are known to cause overdose and death due to respiratory depression. We show that isotonitazene and its metabolite, N-desethyl isotonitazene, are very potent MOR-selective superagonists, surpassing both DAMGO G protein and β-arrestin recruitment activity, which are properties distinct from other conventional opioids. Both isotonitazene and N-desethyl isotonitazene show high potency in mouse analgesia tail-flick assays, but N-desethyl isotonitazene shows longer-lasting respiratory depression compared to fentanyl. Overall, our results suggest that potent MOR-selective superagonists may be a pharmacological property predictive of prolonged respiratory depression resulting in fatal consequences and should be examined for future opioid analgesics.

So even after being modified in the body, its metabolite has a direct path to the mu-opioid receptor. And that "longer lasting" part likely means that it is stickier once it gets there.

Do you have a link that discusses why this is true? I carry naloxone on-duty for my EMS shifts, but currently only 2 doses...

The NIH tried to answer that exact question just 6 weeks ago.
Their conclusion:

Conclusion: This scoping review reveals a paucity of data on nitazene compound overdoses and identifies a gap in our current opioid crisis response. Most nitazene cases reviewed involved hospitalization, had high naloxone dosing, and relatively long LOS. Differences in naloxone dose and hospital LOS could underscore the unpredictable and potent nature of these substances.

If you hunt around for mentions of ER treatment for nitazene with Naloxone, I think it would be fair to say it has a reputation for lengthier stays and more Naloxone consumption. Google AI is quick to say that it can require multiple doses.
I grew up in the '60's and '70's when most official sources of information had everything bad to say about any non-Rx drug other than alcohol and nicotine. So, I can't help looking at much of this with some skepticism.

 

[berkeman]

First, I need to say I am less than happy about Googles use of AI. Before AI, it was much easier to find references. With AI, I often get more information than I can verify - and that is certainly the case in this instance.

Yeah, I need to figure out if there's a way to turn off the "AI Search" feature in Google searches. That is really obnoxious. Off with a mission now...

 

[sbrothy]

Do you have a link that discusses why this is true? I carry naloxone on-duty for my EMS shifts, but currently only 2 doses...

I've seen at least one person who only regained conciousness after the second dose was administered though I don't know what opiate (or opioid) he took. He definitely IV'ed it though.

If you look heroin up at drugsdata.org you'll be shocked at how adulterated it is. An addict is lucky if there's any diamorphine in it at all!

Here's a typical list from one sample:

4-ANPP
Fentanyl
Xylazine
Procaine
Caffeine
Cocaine
Ethyl-4-ANPP
Heroin
4-Fluorofentanyl
Lidocaine
Phenethyl 4-ANPP
6-Acetylmorphine

 

[BillTre]

Drug interactions with agonists and receptors wrt longevity of receptor occupation can be affected in more than one way (this is ignoring what it takes to get the drug to the receptor):

• how strongly the agonist (a binding partner for the receptor) binds the receptor. The stronger it binds, the longer it will reside on the receptor.
• Some agonists breakdown rapidly (or get removed from the site of the receptor, like at a synapse), some don't. This affects its presence near the receptor to bind it again if it comes off the receptor.
• The binding of some drugs will put the receptor into an overly active state which can produce a stronger response that it would to a normal agonist.

 

[sbrothy]

Got my testkits from my supplier. I'm gonna hand these out downtown:

They are actually free but a lot of these people don't even have the wherewithal to even order them, or maybe they miss an address. Who knows...

 

[sbrothy]

[...] It's also likely that the production equipment is also used for other drugs so cross contamination appears to be common. [...]

Which screams to the heavens in both idiocy and infamy. I mean if you can afford a complete laboratory why not an autoclave or simply to inconvenience yourself with at least a cleanup step in there somewhere. One would expect these people to have just a little - if not decency, which is out of the question of course - but then at least just a smidge of pride in what they do. But apparently they really just don't give a s...!

Scary.

 

[Astro Student]

Whenever these opiods are mentioned they usually mention that e.g. fentanyl is "50 times stronger than heroin" and "100 times stronger than morphine". Now it's nitazene which the public is told is everything from "much stronger than heroin" and "200 times stronger than fentany"!

Do these numbers make sense at all? How do they arrive at them? Kill thousands of mice?

Others gave good responses that explain things well, but I figured it worth mentioning the pharmacodynamic principles of efficacy and potency. They are distinct, intrinsic properties of drugs.

 

[sbrothy]

Others gave good responses that explain things well, but I figured it worth mentioning the pharmacodynamic principles of efficacy and potency. They are distinct, intrinsic properties of drugs.

View attachment 362260

Sounds convincing. Did you study pharmacology? This is particularly ironic because I've just bitched about the difference in pronunciation between eifficiency and efficacy in another thread!

 

[Astro Student]

Sounds convincing. Did you study pharmacology? This is particularly ironic because I've just bitched about the difference in pronunciation between eifficiency and efficacy in another thread!

I've studied some pharmacology as a part of my training, but I'm not an expert.

Fentanyl also happens to be the textbook example of a high potency drug. Clinically, the observed potency depends on many factors--one such being lipophilicity. Fentanyl is highly lipophilic and crosses the BBB more readily. Interestingly, this is also likely why fentanyl has a favorable side effect profile compared to morphine at equianalgesic doses in the peripheral nervous system, like reduced risk for constipation in non-oral routes of administration. The formal definition of potency has fewer variables.

 

[Laroxe]

Opiates generally bind to their target receptors quickly and effectively, surprisingly the nitazenes with a greater binding affinity have far less persistence in the body, morphine having a drug half life of anywhere from 1 to 7 hours while with nitrazines this is usually less than 10 minutes.
Naloxone, which is also a close relative of Morphine with a similar chemical structure, has a greater binding affinity and for reasons not well understood has an antagonistic effect on the receptor, countering the agonistic effect of the opiates. As the most dangerous effect of opiates is in their potential to depress respiration, Naloxone, rapidly and effectively reverse this, though its effects are short-acting, and the dose needs to be commensurate with the opioid effect.

It's not uncommon for the management of overdose to require multiple doses of Naloxone along with monitoring of the blood oxygen levels. I thought the NICE guidelines might be interesting. The second link describes some of the physiology, which can be difficult to follow but can still provide some useful information.

https://bnf.nice.org.uk/drugs/naloxone-hydrochloride/

https://pmc.ncbi.nlm.nih.gov/articles/PMC9424762/

 

[sbrothy]

I'm sorry, but I'm wondering why the discussion of Google AI came up in the middle of this thread. I use duckduckgo.com as I gave up on google long ago because it seemed to be "sheltering" me from "bad" search results. Does google AI a have noticeable impact on searches in relation to this subject?

 

[berkeman]

It's not uncommon for the management of overdose to require multiple doses of Naloxone along with monitoring of the blood oxygen levels.

A good reminder to monitor pulseOx in field Pts when administering Narcan. Thanks.

 

[sbrothy]

A good reminder to monitor pulseOx in field Pts when administering Narcan. Thanks.

Absolutely. This must be EMT 101. The little clamp that goes on the ear flap. Even if the patient is not completely out there's still the danger of brain damage. I'd love to have one of those if I could only persuade random addicts to let me take a reading, fat chance though!

EDIT: Yeah, I know they have those for the fingers too, but in my, admittedly secondhand, "experience", the ear flap one is more precise.

EDIT2: They're not even that expensive. Good thing I'm not a parent or my private "apothecary" would be filled with gadgets like these and a black box filled with paranoia.

 

[AlexB23]

The same problem is in the US right now. There is a high usage of fent in 2025. It can be ascribed to doctors over prescribing these substances. Then, the second reason is money. When more of these hit the streets, profit is to be made. Sadly, many people have passed away because of this.

https://pmc.ncbi.nlm.nih.gov/articles/PMC6984757/

 

[sbrothy]

Opiates generally bind to their target receptors quickly and effectively, surprisingly the nitazenes with a greater binding affinity have far less persistence in the body, morphine having a drug half life of anywhere from 1 to 7 hours while with nitrazines this is usually less than 10 minutes.
Naloxone, which is also a close relative of Morphine with a similar chemical structure, has a greater binding affinity and for reasons not well understood has an antagonistic effect on the receptor, countering the agonistic effect of the opiates. As the most dangerous effect of opiates is in their potential to depress respiration, Naloxone, rapidly and effectively reverse this, though its effects are short-acting, and the dose needs to be commensurate with the opioid effect.

It's not uncommon for the management of overdose to require multiple doses of Naloxone along with monitoring of the blood oxygen levels. I thought the NICE guidelines might be interesting. The second link describes some of the physiology, which can be difficult to follow but can still provide some useful information.

https://bnf.nice.org.uk/drugs/naloxone-hydrochloride/

https://pmc.ncbi.nlm.nih.gov/articles/PMC9424762/

If I understand you correctly Naloxone binds more effectively to receptors in the brain and stays there for longer time, is that correctly understood?

EDIT: No I think I got this wrong with regard to the time thing.

The same problem is in the US right now. There is a high usage of fent in 2025. It can be ascribed to doctors over prescribing these substances. Then, the second reason is money. When more of these hit the streets, profit is to be made. Sadly, many people have passed away because of this.

https://pmc.ncbi.nlm.nih.gov/articles/PMC6984757/

Ironically, since the Danish firm Novo Nordisk refused to sell Phenobarbital for executions, I've wondered why not use some of all that seized Fentanyl. I say this a little tongue in cheek, of course the drug would have to be cleansed properly for human "consumption". Besides, Nitrogen would probably be a more humane solution anyway. Not that I'm a fan of capital punishment but it seems it wont go away, and I have enough imagination to understand the relatives of victims.

BTW: Let's not turn this into a political discussion as per the rules of the forum. Just my 2 cents and as I said a little tongue-in-cheek.

 

[sbrothy]

Another thing I was thinking though: The Raman spectrometer I posted the DIY specs for could maybe now be replaced by an Arduino sensor package. Anyone seen anything in this regard?

EDIT: s/NMR machine/Raman spectrometer

I was corrected in another thread that this is not a mass spectrometer, but simply a Raman-spectrometer. Just saw this so I thought I'd correct it here too.

 

[AlexB23]

If I understand you correctly Naloxone binds more effectively to receptors in the brain and stays there for longer time, is that correctly understood?



Ironically, since the Danish firm Novo Nordisk refused to sell Phenobarbital for executions, I've wondered why not use some of all that seized Fentanyl. I say this a little tongue in cheek, of course the drug would have to be cleansed properly for human "consumption". Besides, Nitrogen would probably be a more humane solution anyway. Not that I'm a fan of capital punishment but it seems it wont go away, and I have enough imagination to understand the relatives of victims.

BTW: Let's not turn this into a political discussion as per the rules of the forum. Just my 2 cents and as I said a little tongue-in-cheek.

Yeah, that is true. Fent is pretty deadly stuff, so in theory , it could be used for penalties. However, I am against capital punishment. It is good that Novo Nordisk stood up and did the right thing. Now, the fent manufacturers should do the right thing and stop making that stuff.

 

[sbrothy]

Yeah, that is true. Fent is pretty deadly stuff, so in theory , it could be used for penalties. However, I am against capital punishment. It is good that Novo Nordisk stood up and did the right thing. Now, the fent manufacturers should do the right thing and stop making that stuff.

Yeah, unfortunately the chances of the last thing are slim to non-existent. Also, I haven't kept up on the Novo Nordisk thing. I just remember it being a problem.

 

[AlexB23]

Yeah, unfortunately the chances of the last thing are slim to non-existent. Also, I haven't kept up on the Novo Nordisk thing. I just remember it being a problem.

Yeah, corporate greed is an issue these days.

 

[sbrothy]

Yeah, corporate greed is an issue these days.

Although this seemed to be an example of the opposite didn't it?

 

[AlexB23]

Although this seemed to be an example of the opposite didn't it?

Yeah, Nordisk did the right thing. A rare win

 

[berkeman]

If I understand you correctly Naloxone binds more effectively to receptors in the brain

Yes.

EDIT: No I think I got this wrong with regard to the time thing.

Yeah, as @Laroxe said, the effects of Narcan are short-lived, like 20-30 minutes or so. That's why it's still important to get the patient to the hospital even if they claim they are fine after they start breathing and wake up.

 

[BillTre]

Fentanyl is probably prescribed a lot because it works well as a doctor would want it to be used. I was prescribed it for after my gall bladder removal. My wife had some prescribed after her knee op. Didn't need to use it and took it to the drugstore's drug disposal bin. Some say it is over prescribed.

WRT to capital punishment:
Why not do what vets do to put down dogs. That works fast and dependably, is painless, is easy to administer, and does not present a hazard to bystanders as Fentanyl might.
I don't see why most considerations of safety for human consumption if the goal is for that person to be dead.

 

[sbrothy]

[...]
I don't see why most considerations of safety for human consumption if the goal is for that person to be dead.

I agree, but ironically the government still wouldn't use a drug not clean enough for human (as I wrote in quotes) "consumption", even for adminstering the death penalty. It makes no sense, but then again neither does the electric chair.