Fentanyl Crisis - Next up, Nitazenes

4DQSAR

4DQSAR

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www.theguardian.com

Did breakthrough in US fentanyl crisis start in China?

US overdose deaths have plunged, and some experts point to moves to restrict Chinese precursors
www.theguardian.com www.theguardian.com

Long ago China banned the immediate fentanyl precursors and the result was simply semi-legitimate chemical companies in Mexico were buying pre-precursors from China and converting them INTO the original precursors. In fact, I can imagine a similar ecosystem to the Gong Kai digital arena with middle-men who are comfortable with 10-15% profit to undertake legitimate work.

So it is no surprise to me that in light of the Don's visit to China, the Chinese have indicated to suppliers that leading up to the visit, selling to Mexico (and India - a trans-shipment point) were out. But the market remains and to the best of my knowledge, precursors to nitazenes and possibly even some finished product is not controlled in China or Mexico.

Then add to this the fact that Carfentanil is now appearing.

In short, every time a chemical is legally controlled, people either find the most potent analogue to make precursor purchaces hard to spot and/or simply swap to the next class on the list.

I still cannot explain why 4-phenyl phenapromide or even more potent derivatives have yet to turn up. Not as well explored BUT we know of several modifications to the phenapromide scaffold that comfortably puts them into the same potency bracket as fentanyl. After all, those derivatives OVERLAY fentanyl and the final step, the formation of that amide - that is likely IDENTICAL to the last step of fentanyl synthesis.

None of the above is secret. It would be nice to think that someone put some thought into POTENTIAL fentanyl alternatives and had those phenapromide precursors controlled, but so far, law enforcement has always been reactive, not proactive.
 
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Hasn't there also been somewhat of an emergence of orphine opioids like Brorphine and recently Cyclorphine.
Also SR 17018
 
There has but from the little I know, that class MAY not be quite the goldmine Chinese manufacturers hoped. Brorphine has killed a few, cyclorphine seems to be used more as a cut than a product, likely because while it may well be equipotent with carfentanil in animal models of pain, every other example of an N-2-cyanoethyl moiety has demonstrated far more analgesia than a simple N-methyl BUT every single paper noted two things.

1-It did not SUBSTITUTE for morphine which should at least makes people wonder just what type of analgesic is is.
2-In every study, where the N-2-cyanoethyl moiety was tested, it was shown to be unselective i.e. it mediates that increased analgesia via KOR (dysphoric/hallucinogenic) and DOR (pro-convulsant) opiate receptors.

Now there MAY be a window but it's gone from multiple websites banging on about how amazeballz it is to quietly being traded as a cut.

It is just a hypothesis but having looked at around 100 different medically used opioids that were redirected to the street, one may have potency OR euphoria - not both. Certainly fentanyl derivatives and the more potent nitazenes only seem to produce a 'plastic euphoria' at doses perilously near to toxic doses. I suggest it's mean receptor-occupancy time. High affinity means long receptor-occupancy times and the euphoria is mediated by the binding-unbinding cycle so only in the 'death zone' do they produce any psychoactive effect.

Long, long ago I was prescribed fentanyl patches and if used as stated, it was in fact very good. It controlled the pain without any other notable effects. But if euphoria is the goal, it's a terrible choice.

In the 1980s the UK had all manner of dubious opioids if only because Janssen had somewhat 'flooded the zone' and even stated that he had an opioid appropriate to all legitimate usages. But even his own PR team were less than honest. I saw an ad for dextromoramide (Palfium) which claimed 'high oral bioavailability'. Well, that's a subjective term but in the very same year an academic paper BY Janssen noted oral bioavailability was around 20%.

So peach Palfium is something even dependent opioid users either treated with respect or died. I did ask BLers and one chap recalled a friend nicknamed 'Skaggie Maggie' who was found dead in the toilet of an insalubrious pub. 10mg may not sound much, but 150mg of morphine DOES. She had whacked up several. Diconal was another uniquely British disaster but I noted that US clinicians used to have the option of prescribing oxymorphone (Opana) and Levo-Dromoran (levorphanol). Both fed the needle.

In essence, the best option is an opioid that is MORE active when consumed orally. You may be surprised to learn that oxycodone is an example. But even them, if it can go in a pin, it WILL go in a pin.

It's entirely practical to design a prodrug that essentially means that any and all parentheral routes will yield no effect. Again, this is known. Bentley and Janssen both developed such things 60+ years ago. Heck, even oxycodone from a century ago turns out to mediate around 50% of it's activity due to O-demethylation. But I suspect a parentheral route will be subjectively different as it's action is akin to simple dihydrocodeine. It's active as it is but O-demethylation plays an important role.
 
All of this, of course, is a product of the war on (some) drugs. It never ceases to amaze me how desperate people will find a way to get high if they cannot find a legal means to do so. It's just plain tragic, really.
 
I can only agree with @Flynnal - it's interesting to note that Australian archeologists discovered the 12,000 year old Pituri Trade Networks in Western Queensland where a nicotine-containing herb was traded. I think I'm correct in stating that the ONLY culture that had no access to psychoactives were the Inuit (the Yupik apparenly found nicotine in a fungus and some subgroups also discovered the fly agaric mushroom). It seems that seeking an altered state of consciousness is an intrinsic human drive be it anywhere on the scale from the religious rite to the hedonistic flight.

It's simply the case that quite legitimate research still takes place but there already dozens of scaffolds that have yet to be controlled and at what point does the sheer number of controlled chemicals become too costly to police?

I'm a firm believer in the fifth freedom. All well informed adults should be allowed to purchase and consume (or equally not purchase and consume) whatever they choose to. The only caveat being those that apply to alcohol - driving and operating heavy machinery while intoxicated should be enforced as that puts others in danger.
 
4DQSAR said:
I can only agree with @Flynnal - it's interesting to note that Australian archeologists discovered the 12,000 year old Pituri Trade Networks in Western Queensland where a nicotine-containing herb was traded. I think I'm correct in stating that the ONLY culture that had no access to psychoactives were the Inuit (the Yupik apparenly found nicotine in a fungus and some subgroups also discovered the fly agaric mushroom). It seems that seeking an altered state of consciousness is an intrinsic human drive be it anywhere on the scale from the religious rite to the hedonistic flight.

It's simply the case that quite legitimate research still takes place but there already dozens of scaffolds that have yet to be controlled and at what point does the sheer number of controlled chemicals become too costly to police?

I'm a firm believer in the fifth freedom. All well informed adults should be allowed to purchase and consume (or equally not purchase and consume) whatever they choose to. The only caveat being those that apply to alcohol - driving and operating heavy machinery while intoxicated should be enforced as that puts others in danger.
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After much thought, I've had an epiphany here and there, but one came last night and it was, to put it mildly, terrifying. There is only one caveat here. I agree with this in principle. However, there are many pitfalls, one being someone who is deranged and has a desire to kill others. For example, a combination of amphetamines and barbiturates could enable someone to act on their desires. Basically, this combination can turn the sweetest person into a deranged psychopath in record time.

That's the only concern. Someone under the influence of drugs who brutally murders someone else. Perhaps it's someone they hate, someone who has ruined their lives or their and their families' lives, or any number of other people whom they want to kill, but obviously would never act on since they do not have the biochemistry that would be conducive to such brutality. Enter amphetamines and barbiturates, a good example would be Desbutal®, a pentobarbital (Nembutal®) and methamphetamine (Desoxyn®) combo, or Dexamyl®, an amobarbital (Amytal®) and dextroamphetamine (Dexedrine®) combo. These drug combinations can turn the nicest people into ice-cold, bloodthirsty killers in no time at all. They always had the desire, a longing to kill someone for whatever reason, payback, etc. They have the desire. Give them the drugs, and it erases all inhibitions and other mechanisms that would otherwise prevent these people from acting out these brutal fantasies.

That is literally the greatest fear with allowing everyone to get whatever drug they want. The homicides, the murders, the violence that certain drug combinations could provoke.

Something to think about. I agree with you for the most part, but some drug combinations would be very problematic. Amphetamine and barbiturate combos being a prime example. I don't care about people suiciding with barbiturates because it sure beats someone ending up painting the front of some poor truck/train driver's front caboose with their brain matter or having paramedics scrape their guts off the sidewalk of a very tall building, not to mention drownings where rescuers need to risk their own lives to try to recover and revive would-be suicides (eg Golden Gate Bridge, etc). But homicides from mixing barbiturates with amphetamines are another problem altogether.
 
@Flynnal - I don't think barbiturates are any worse than alcohol. Certainly I've noted that the people who got nasty when drunk were the ones who got nasty if they consumed hypnotics. But not just barbiturates. I think all the hypnotics that act on the GABA receptors have that ability to disable a person's executive control.

Even if legal, I don't see many people desciding that barbiturates were their 'drug of choice'. In cases where people mixed uppers and downers, yes, unpredicatble certainly is common but planned out attacks? Never seen that. Punching a random stranger for no apparent reason seems to be the result. People not thinking beyond the next moment.

I just think if you excluded certain classes of drug, you would have people seek them out just because the lure of the forbidden is so powerful.
 
4DQSAR said:
@Flynnal - I don't think barbiturates are any worse than alcohol. Certainly I've noted that the people who got nasty when drunk were the ones who got nasty if they consumed hypnotics. But not just barbiturates. I think all the hypnotics that act on the GABA receptors have that ability to disable a person's executive control.

Even if legal, I don't see many people desciding that barbiturates were their 'drug of choice'. In cases where people mixed uppers and downers, yes, unpredicatble certainly is common but planned out attacks? Never seen that. Punching a random stranger for no apparent reason seems to be the result. People not thinking beyond the next moment.

I just think if you excluded certain classes of drug, you would have people seek them out just because the lure of the forbidden is so powerful.
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Good argument. After some further research there are more dangerous combos than these anyway. It's just that those two came to mind first.

Barbiturates are the drug of choice for suicide, so that could present a problem, but on the other hand, forcing people to end their own lives using horrible and violent methods is in my honest opinion worse than allowing them to use drugs to effect the same result. On the whole I generally don't agree with suicide, but sadly for me if my neurological condition deteriorates to where I 1/ cannot see, or 2/ cannot hear even with cochlear implants, 3/ becoming disabled and cannot use my arms or legs, then I think I'd consider an exception.
 
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