Finally! All the benefits of the opioids, with none of the dangers.
For clarity: I'm referring to all the previous attempts to "fix" the synthetic opioids, each of which ended up making a stronger, more dangerous opioid.
Not just OxyContin. Also Heroin, Meperidine and Tramadol.
We get another "morphine, but safe this time" in pretty reliable 40 year intervals. I guess someone decided OxyContin doesn't count and we are due for another one
To be honest I would prefer addicts could get heroin prescribed. The primary danger of street drugs is the inconsistent purity and chemicals it’s cut with. If it was pharmaceutical grade and everyone prescribed was on a list, we would have fewer overdoses and a better understanding of who to put in treatment
Most heroin overdoses happen either from a sudden increase in supply purity, or from an abstinent addict relapsing and taking their regular dose without realizing they have lost their tolerance.
Any kind of rational change in policy is not happening as long as entire lucrative industries of policing, health care and religion-as-a-social-service are dependent on the dependent.
It's such things that reveal the cruelty in our sociaties. The evidence is very clear; it reduces deaths and improves health, while also reducing crime. But its still not the default the world over because its apparently a hard sell to give addicts anything for free. The other comments here show the sentiments nicely.
There is no need to give it for free. It costs very little to produce, most of the cost is just risk and irregular logistics. Just sell it over the counter at walmart for $5 just like they do rat poison, bottles of vodka, and ammunition.
You might say they won't be able to sell enough foodstamps or welfare even then to come up with the money legally, but it'd still be way less crime.
People don't get addicted to rat poison or ammunition (usually). But you have got a point on vodka. There is little reason to treat alcohol (and worse, nicotine) as any different than most addictive substances. Drug policy is totally irrational
alcohol is a far cry away from opiates. they should just allow everything. its actually effective in drastically reducing abuse. since use is normalized it become easier to have social control form peers etc. and that works really well actually. Additionally it would allow for stable products which means more safe products.
The US did this dance with the devil in the pale moonlight before anyone, way back in the 19th century. Tens of thousands (millions) of wounded soldiers came back from the civil war in chronic pain and addicted to morphine. They put them on "lists" and prescribed them dope and it spiraled out of control. It got so bad that they engineered Heroin to be a safer alternative. And people forget, but the temperance movement wasn't just focused on alcohol. They were the primary forces behind the Harrison Narcotics Tax Act of 1914. And these people weren't bible thumping crusaders, many were like early feminists that lost children\husbands to drugs and alcohol. I think Europe eventually comes around to this same conclusion when enough damage has been done. Metering out hard drugs has always been a road to ruin.
This seems only partially correct. If by "they" you mean Germans then yes, Heroin was engineered by them, or at least first made commercially available by Bayers. The US government had nothing to do with it. It was marketed as a less addictive alternative to morphine although I highly doubt anyone who made it actually believed it was safer. I have no source for this but I think it is a safe assumption to make.
The temperance movement was mainly related to alcohol. There were groups who wanted abstinence from everything but that was not its primary focus. They may have played a part in said act but I don't know. They were definitely not the driving force behind it though. Racism played a bigger role than the temperance movement. The government was also aware there was a very real problem with drug addiction.
Notice the word „decriminalize“, not „legalize“.
It’s about not throwing people already struggling with addiction in jail but rather offering safe alternatives (counseling, safer use, etc.).
The government‘s not passing out drugs in the street, like US media likes to suggest.
Nowadays they're just given methadone or Buprenorphine (other opioids). Having known family members that worked in the clinic, there is no plan to get most of them off of it. It is like other opiate addicts, ~most of them take it until they are dead unless they are just dead set on getting off and willing to live with the fact they might never quite feel 'right' again, although at least it is safer.
Is that such a bad thing? Plenty of people will take medications for the rest of their life -- statins, antipsychotics, antidepressants, ADHD meds, antiretrovirals. The stigma of chronic medicine use needs to go away.
I don't know it's a bad thing, just pointing out, the US does just prescribe opiate addicts more opiates basically for life without a plan to stop it. Responding to "They put them on lists and prescribed them dope and it spiraled out of control ... metering out hard drugs has always been a road to ruin" with the facts that's what we're already doing writ large. The thing many people argue shouldn't become the case is already the case and many are oblivious to it (thinking that it was just a thing in the past we stopped).
It isn't the same drug as fentanyl, but it never really stopped being the plan that we will take people from 'the list' and just keep metering opiates out indefinitely. GGP posted this in a way that seemed to allude this was not currently the case.
Sr-17018 is making rounds now (ok was a year ago) among people using opiates too much. On forums, it is pushed as the miracle stuff which allows lowering dosage without major withdrawal.
It's fantastic, the main Iboga practitioner I work with now mainly works with SR.Its a much easier process. Imidazenil has also come to the scene at much cheaper prices for benzo withdrawals.
0) Zero tolerance! We still remember how it ended last time!
1) But ... pain medication helps against anything. From headaches to hernia to bone cancer (of course in some cases it's in a "die somewhat dignified" sense). And in quite a few cases it's the only thing that helps ... In the medical sense of "helping", after all medicine can't make people live forever so that can't be the goal. The goal is better quality of life, ie. mostly longer life, including the ability to live (think "sing, dance and play tennis") ... and not life at any cost.
The problem here is that this is an entirely correct argument. Some diseases are either incredibly painful or long-term painful. Bone cancer or hernia can serve as examples. We cannot really help such people (by that I mean: not in a way that the pain stops). So can we at least make their life livable?
2) This pain medication sure helps these very seriously ill people well. But X suffering is at least as bad as bone cancer! X then is everything from still serious diseases, psychological suffering, and of course this then goes down and down until someone points out pain medication also helps existential dread and lackluster parties.
Again, all of that ... is true. That's not the problem.
3) The medication becomes the problem. Mostly because of what people do to get money for their fix (and the crime, prostitution, ... that it leads to). But this is not the only problem. It makes people who broke a bone last week go skiing again. And ... I'm almost afraid to say it but you can increase the effect of morphine ... by damaging yourself. You can guess how that ends.
The problem is that pain medication, irrespective of whether it's physically ("biologically") addictive is addictive. Anybody who's had a serious pain for a week, say kidney stones, knows that they would have sacrificed their favorite cat for it to stop. The problem is not just that morphine is addictive. The problem is the pain, and the fact that pain medication is a temporary non-fix.
4) The medication becomes the problem, but doesn't just affect patients. It goes from "you know this funny thing happened to my niece ... and she did it to herself ..." to it destroys families, neighborhoods, childhoods ...
Isn't the entire endgoal of studying medicine and biology to make humans live "closer to forever"? Aren't we working toward expanding human lifespan till we either hit a hard ceiling or approach infinity?
What the surgery actually does is fix 2 disks of your spinal column against each other. It lowers the pain from torture to tolerable and reduces various risks. Also: you won't be so much as sitting up for months. I don't think many people will call that repair. Perhaps mitigation.
I think you are both talking about slightly different things:
* Herniated disk in the spine
* A "hernia": is the abnormal exit of tissue or an organ, such as the bowel, through the wall of the cavity in which it normally resides.[
If you think of your abdomen as a bag full of tubes, a fistula is a hole in the tube that connects to something else. A hernia is a hole in the bag, that the tube can poke through.
On the one hand, I'm sure that the post you're responding to is referencing many previous failed attempts at making non-addictive opioid painkillers.
But on the other, non-sarcastic side... if addiction is the only remaining problem with them, should we care that much?
I.E. if both the chronic and acute health risks are gone (which I don't think they are for a second, but follow me along on this little thought experiment)... does it matter quite so much? Clearly addiction, in the abstract, is not exactly a good thing. But if it's not coupled to risk of death it seems to me it would be a great thing to transition addicted people to, and take away some of the urgency of the situation.
I agree. I would say that I am addicted to caffeine. I definitely get withdrawal symptoms if I don't have a coffee. But since it is so accessible and there are no health risks, it does not affect me negatively to "feed" the addiction.
Not a great analogy. Caffeine is not as addictive as opioids. Opioids strongly stimulate the mesolimbic dopamine pathway, leading to intense euphoria, compulsive use, and severe health and social harm.
I admit that I don't know who Tyler Cowen is, but millions (billions?) of people have drunk coffee daily for centuries and if there were ill effects in the same ballpark as opioids or tobacco by now we would certainly know?
There is even a decent chance that the Industrial Revolution and the phenomenal wealth and progress it's brought was caused by the introduction of coffee to Europe.
A professor of economics has opinions on the health effects of an extremely common substance?
And I have opinions on nuclear energy - but neither of us are worth listening to outside our areas of expertise. Unless you can supply a reason I would bother listening to him as compared to an actual expert on the subject?
Because some dude with no health or nutrition background said uninformed things, that he isn't qualified to have opinions about, on the internet? Come on, now.
By definition addiction involves pursuing substances or engaging in behavior repeatedly despite negative consequences in one’s life.
Any behavior or substance that causes serious addiction is still bad regardless of whether it causes death or other negative health effects. The addiction itself inherently causes suffering because the addict is engaging in something despite the negative consequences in the rest of their lives. The negative consequences cause suffering and the psychological pain of wanting to stop and not being able to stop also causes suffering.
I know some other commenters mentioned caffeine addiction but nicotine and opioids (and also behavioral addictions like gambling) are vastly more addictive than caffeine.
Negative consequences from addiction can involve more than loss of money (although loss of money is still a significant thing of course.) They can cause damage to one’s career, family relationships, friend relationships and so on. Even if the addictive behavior or substance has no other inherent negative health effects.
In high school I had a really bright and motivated friend. He went to an Ivy League school. He became horribly addicted to World of Warcraft as a freshman. He spent so much time playing the game that he damaged his grades and GPA. He almost failed out of school. He had to make serious effort to stay in school. And he had to spend tremendous mental effort to avoid playing additive games anymore. That’s just one example.
> .. if addiction is the only remaining problem with them, should we care that much?
I think we should because it’s undignified to have people who want to stop taking them but are unable to resist the compulsion. I feel the same way about basically every addictive substance. Even if it was freely available and risk-free I still think that being trapped in a cycle of use and withdrawal is such an affront to someone’s dignity that we should still try to prevent that.
There's already buprenorphine and methadone. But, using either means some degree of responsibility, punctuality, etc. So unless you mean freely distributing it with very little process, it wouldn't change much.
Those, from what I understand, don’t hit the same and someone needs to be ready to quit to go on them, they help with withdrawal etc, definitely, but are not always successful as they don’t scratch the full itch. A bit like nicotine replacement therapy
But there’s a whole space of harm-reduction before then, which is where things like the Swiss program to provide heroin in controlled circumstances can fit in.
An opioid without respiratory depresses on problems could fit into that sort of thing pretty well.
I’m in one now. The problem here is meth. But then I’m not in the US and things are different in different places.
It was a thought experiment about addiction if the other negatives could be removed, I doubt we’re actually anywhere close to that anyway, but it might imply that zombification had been solved.
I mean I guess it depends on the level of use? Do you need to be nodding off, drooling on the verge of respiratory collapse to cope with the dread of your situation? (I feel like people are mostly only considering the physical reasons for starting opiates in this post btw). Or is it a more reasonable dose that allows you to participate in society unencumbered by your pains? (Which in any case is a slippery slope with long term use)
and the fun fact, the other new drug targeting the mid-receptor of acetyl-choline that functions like mu-opioid receptor also has the same exact addiction problems.
>each of which ended up making a stronger, more dangerous opioid
This is true of some early opioids like heroin, but with e.g. Oxycontin the problem wasn’t a stronger opioid, it's how it ended up being prescribed.
Purdue's marketing led doctors to prescribe it to more people, in higher doses, and for longer. Oxycontin isn't inherently more dangerous than the dose of immediate release oxycodone or morphine that would have an equivalent effect.
Innovation in opioids shouldn't just be written off. They're still the best (and sometimes the only effective) treatment for a huge number of people, and some new opioids like buprenorphine/combos like Suboxone have real advantages.
The lesson from Oxycontin is more about deceptive marketing and prescribing practices.
I mean if there were no safe dose or usage pattern then I would expect a lot of mothers to leave the hospital with both a newborn and a crippling addiction. The epidural is an opiate like fentanyl.
Adjacent medicines have seen major improvements: eg Ketamine was a significant improvement from PCP (notably, less psychosis and safe enough to use off the battlefield / with children)
“Removing the worst and most fatal danger” is a laudable goal with Fentanyl given the absurd rate of ODs
As have the opioids buprenorphine and Suboxone (buprenorphine/naloxone), which are genuinely useful treatments for addiction and have much lower risks of abuse.
We really could use better treatments for chronic pain.
I've found low dose naltrexone to be somewhat effective for severe chronic pain. Not as good as opiods.
THC can also help somewhat, but its action seems so dissociative. At an effective level for chronic pain, I'm sleepwalking though the day.
Opioids or their analogues cause or complicate bowel issues. Four years of 200mg/day Tramadol really helped me, but it shredded my gut. Getting off Tramadol wasn't hard for me. I'd stay on it were it not for the gut issues.
As an aside, lacing hydrocodone with acetaminophen is truly a horrific practice. Doctors prescribe this to patients on hepotoxic drugs and are shocked when they get liver damage.
I have 2 family members for whom Tramadol opened the door for severe addiction. One is now on regular morphine, the other had psychosis. I know it obvisouly depends on the individual, just to dilute your very rosy comment
Right. Opioids are an absolute terror to one's digestive system. When I had chronic pain I would rather have just accepted the pain than deal with the gut consequences.
LDN is an interesting one since it just stimulates your body to generate its own endorphins.
> I've found low dose naltrexone to be somewhat effective for severe chronic pain. Not as good as opiods.
When I could get 7oh, it worked well for moderate break-thru (ibuprofen) pain (muscle, joint). I also tried a month of using it regularly wasn't happy overall. I didn't get any withdrawal on stopping tho.
Is fentanyl even that big of an issue in a clinical setting? It's not like it's the go to opiate of choice for general pain anyway.
The problem with fentanyl is that it is easy to make and smuggle and we managed to leave a giant black market hole to be filled when we went ape shit about oxy, which was an objectively better situation than we are currently in with street opiates.
One of the big problems with anesthesia is balancing respiratory depression while medicating the patient enough to manage the symptoms. Fentanyl is used in anesthesia and it causes respiratory depression.
A strong pain medication that doesn't slow or stop breathing would significantly improve the safety of anesthesia.
It's a weird framing. Fentanyl is already very safe in a healthcare setting. It's only dangerous in off-label street use, where dosage is uncontrolled and use isn't being monitored by trained staff. Do we think cartel labs are going to switch to a safer novel opiate? I'm sure they don't care about any relevant patents, but they already have a pipeline/formulation for fentanyl.
As a recurring kidney stone sufferer I am very thankful for fentanyl for my lithotripsy procedures. I hope we continue to make progress on effective pain medications and don't knee-jerk take them away.
I have several naloxone kits in my house and my kids carry them in their backpacks. I'm pro harm-reduction.
With that in mind, what I'm "actually trying to say" is that
a) any time we can make a medication less harmful, that's a good thing; and,
b) if this new molecule relieves pain as well as fentanyl does, it will surely be used by people who are addicted to drugs or who are using drugs recreationally.
The bigger question that goes way beyond the scope of Scripps' research contribution is whether our society can begin to accept that people use drugs like fentanyl to treat depression, trauma, anxiety, and pain of all sorts. And that criminalizing their efforts to treat themselves does not lead to any improvement in their wellbeing or the wellbeing of our society.
I don’t make them do that. They do it because they want to be ready to help in the seconds that matter if someone has an overdose. This is the sad reality they inhabit.
I wonder if this modification brings it closer to the mitragynine from kratom, which has opiate like pain dulling effects with very minor or no effect on breathing.
I hope so because the administration is looking to really fuck over medical research by making the 7-OH stuff a schedule 1 narcotic, when it has so much potential for improving anesthesia and pain management by removing respiratory depression from the pain killing element of the anesthetic cocktail.
My understanding is that mitragynine is an mu-opioid partial agonist which limits its impact even in high doses. This is sort of in the same realm as Buprenorphine. Google claims it also doesn't recruit beta-arrestin but admittedly I'm out of my depth here. Presumably this proposed fentanyl replacement is still a full mu-opioid agonist for efficacy.
Except even as the press release states right off the bat, Fentanyl is efficacious, cost-efficient, and can be made widely available in areas like the global south without extensive pharmaceutical production infrastructure in place. The overdose crisis is in fact not really something that came out of the drug itself, just as the prevalence of Oxycodone before the enforced policy change shifted the usage patterns into a far more dangerous direction in heroin and tar and then, adulterated versions with fentanyl. People who are prescribed fentanyl for pain are not dying in droves. If you've had surgery, you may have been given fentanyl. If you're reading this, you, like most people, survived it just fine.
The crisis is one created by policy and cannot be eliminated on the pharmaceutical end. This isn't a case of methanol being sold as ethanol or SSRIs having less than ideal efficacy rates while causing widespread sexual dysfunction at a rate much higher than originally thought, or Zolpidem leading to over a hundred observational notes published in medical journals describing dangerous activity performed even on small doses followed by anterograde amnesia that certainly is a real thing that is also potentially dangerous, but incredibly difficult to study. Those effects are happening when the medication is taken as prescribed Do people take those without prescriptions? Of course, but one assumes the risk, and also, anyone ever seen a Zoloft pill mill?
Fentanyl had been diverted in small quantities onto black market supply chains for as long as it has been available. You can absolutely get an Actiq Pop in 2006 if you really wanted it, and the thing is a lollipop for crying out loud. It didn't cause widespread overdoses, it didn't even cause any significant black market demand. It was at best a curiosity. It's hard to quantify a subjective experience, but generally it was regarded as "not fun" anecdotally. Heroin is fun. Hydromorphone is even more fun but the best ROA leaves you with a 5-10 minute high at best and takes about that much time to prep. Oxycodone was fun but since the DEA made sure that it was as difficult to obtain as possible all of a sudden and what was available was spiked with enough APAP so that your liver might give out before you overdosed, well, what does cutting off the supply but leaving the demand in place do? The crisis as we know it today was inevitable in some form. It's created by policy, which is not set by scientists, and in fact when hydrocodone/APAP was rescheduled for Schedule II a specific reply to patient access concerns was "we don't take that into account", according to the DEA. Thanks for the candor, sadly we've gotten very little of it in the years since.
But of course, even on the black market, people overdose in a manner that is to a degree predictable. Long term users with steady supplies - say, everyone who's on a benzodiazepine long term - aren't overdosing regularly (yes, the LD50 of benzodiazepines generally makes overdosing on it alone very difficult if not impossible, but kicking it cold turkey does actually cause deaths from seizures and when mixed with another depressant like alcohol it becomes almost trivial to overdose on it, arguably making it at least in theory a more dangerous drug if one takes the view of the DEA). They are mostly able to obtain legitimate, low cost, and frequently entirely legal versions of, well, name the variety. From Triazolam (3 hour half life) to Midazolam (water soluble) to Etizolam (scheduled into schedule I based on 4 cases in Norway where when mixed with another depressant patients ended up in the ER. All survived and were discharged almost immediately. The reason why the DEA laundered cases in Norway through the FDA to justify at first an emergency scheduling and then turned it into a permanent one? Because they couldn't find any cases that demonstrated the purported danger in the US or Canada.) Overdoses happen when someone takes too much of a substance, but "too much" is difficult to determine when you don't have a reliable supplier in terms of quality and adulteration, but also, because tolerance gets built up so that long term users can use prodigious amounts and be just fine. But how do we make sure that nobody knows where their tolerance is at? Non-medically assisted, pseudoscientific "sobriety help" like AA or its variants that are ordered by the court, and of course, probation, testing, in-patient medicaid fraud mills, you name it. Since none of these actually do anything except use homebrewed aversion therapy or even less efficient, shame, to achieve what is basically not even a real goal but is tied to the criminal justice system, congrats, you have the perfect storm of demand not knowing how much to actually demand for. Fentanyl being the adulterant made this last inevitable easier, but it only hastened what had been happening for quite some time. When heroin supply on streets increased, fentanyl related deaths began decreasing. Wonder why? It's correlative, but observational studies take a lot more data and a lot longer time periods, although it would certainly follow previously observed patterns.
This may be interesting as a scientific venture, but treating it as anything but that is foolhardy and misguided. We know how to control pain. We know how to reduce the harmful externalities that form part of the definition of substance use disorder since we, as in society and lawmakers elected by us, are responsible for those harmful externalities in the first place. Fentanyl is not the problem. Making sure that there's no safe way to reduce potential harm associated with, ultimately, a personal choice favored by some but certainly not all as recreation, killed the hundreds of thousands since Lou Reed sang Heroin and put it onto the Velvet Underground and Nico. Why are we still acting brand new?
I’ve been to a few AA meetings when I was trying to get my mom sober and I never got the vibe that it was about “aversion therapy” for alcohol. The whole point seemed to be to discharge your egotistical need to be “in control” of the alcohol and accept that it was taking over your life despite your best efforts. You were then supposed to seek help from the people in the group to try to keep that from happening. There wasn’t really a culture of shame but rather acceptance there. And they also pushed a lot of ideas like repair after rupture that are a part of normal human relationships. So I don’t really buy what you’re saying here.
I mean that is great. But the overuse of opioids in Us is crazy. I am from europe, had broken arm, sprained ankles, broken fingers, root canals done, appendix operation and never got anything stronger than ibuprofen. Hopefully, the prescription craziness is getting better.
Over the last 10 years, state medical boards have dramatically cut back on opioid prescriptions (which happens to correlate with the rise of fentanyl use). Even those with chronic pain with a history of prescription were cut back. It's unfortunate because for some people, opioids really are the only thing that works for treating incurable pain but the downside is that they develop tolerances and they become ineffective over time. It really would be a miracle if we could invent a pain medication that is non-addictive.
However, a new type of pain medication doesn't remove the current opioids available on the street. Legalization of marijuana is one thing, it's relatively low risk but I don't see legalization of opioids ever happening because absolutely nothing can replace the warm blanket feeling that they provide.
It's been cut back pretty hard in the last 5 or so years? Even after major surgeries you get very short prescriptions, or only get them in the hospital under monitoring. I think we got a little too cautious personally but it's definitely trying to swing the curve away.
They're not going to prescribe anything serious for those conditions in the US, either. You might get as much as codeine with acetaminophen. But there's a good chance you'll get nothing more than ibuprofen and local anesthesics.
Finally! All the benefits of the opioids, with none of the dangers.
For clarity: I'm referring to all the previous attempts to "fix" the synthetic opioids, each of which ended up making a stronger, more dangerous opioid.
The danger of addiction, which is very significant, with opioids doesn’t go away with this modified design.
Unless you’re being sarcastic and referencing the lies the Sackler family used to get OxyContin popular..
That being said it is indeed quite cool that they modified the drug to decrease the respiratory depression.
Not just OxyContin. Also Heroin, Meperidine and Tramadol.
We get another "morphine, but safe this time" in pretty reliable 40 year intervals. I guess someone decided OxyContin doesn't count and we are due for another one
To be honest I would prefer addicts could get heroin prescribed. The primary danger of street drugs is the inconsistent purity and chemicals it’s cut with. If it was pharmaceutical grade and everyone prescribed was on a list, we would have fewer overdoses and a better understanding of who to put in treatment
Most heroin overdoses happen either from a sudden increase in supply purity, or from an abstinent addict relapsing and taking their regular dose without realizing they have lost their tolerance.
Any kind of rational change in policy is not happening as long as entire lucrative industries of policing, health care and religion-as-a-social-service are dependent on the dependent.
This cuts to one of the more important points here. Rent seeking behavior in public health is crazy to witness.
Don’t forget for-profit prisons!
Im alwys stunning about the story that Heroin was market as non-addictive product by Germany Company BAYER:
https://de.wikipedia.org/wiki/Heroin#/media/Datei:Bayer_Hero...
It's such things that reveal the cruelty in our sociaties. The evidence is very clear; it reduces deaths and improves health, while also reducing crime. But its still not the default the world over because its apparently a hard sell to give addicts anything for free. The other comments here show the sentiments nicely.
There is no need to give it for free. It costs very little to produce, most of the cost is just risk and irregular logistics. Just sell it over the counter at walmart for $5 just like they do rat poison, bottles of vodka, and ammunition.
You might say they won't be able to sell enough foodstamps or welfare even then to come up with the money legally, but it'd still be way less crime.
People don't get addicted to rat poison or ammunition (usually). But you have got a point on vodka. There is little reason to treat alcohol (and worse, nicotine) as any different than most addictive substances. Drug policy is totally irrational
alcohol is a far cry away from opiates. they should just allow everything. its actually effective in drastically reducing abuse. since use is normalized it become easier to have social control form peers etc. and that works really well actually. Additionally it would allow for stable products which means more safe products.
Welcome to Switzerland. Where this exact approach is working well for many many years now.
The US did this dance with the devil in the pale moonlight before anyone, way back in the 19th century. Tens of thousands (millions) of wounded soldiers came back from the civil war in chronic pain and addicted to morphine. They put them on "lists" and prescribed them dope and it spiraled out of control. It got so bad that they engineered Heroin to be a safer alternative. And people forget, but the temperance movement wasn't just focused on alcohol. They were the primary forces behind the Harrison Narcotics Tax Act of 1914. And these people weren't bible thumping crusaders, many were like early feminists that lost children\husbands to drugs and alcohol. I think Europe eventually comes around to this same conclusion when enough damage has been done. Metering out hard drugs has always been a road to ruin.
This seems only partially correct. If by "they" you mean Germans then yes, Heroin was engineered by them, or at least first made commercially available by Bayers. The US government had nothing to do with it. It was marketed as a less addictive alternative to morphine although I highly doubt anyone who made it actually believed it was safer. I have no source for this but I think it is a safe assumption to make.
The temperance movement was mainly related to alcohol. There were groups who wanted abstinence from everything but that was not its primary focus. They may have played a part in said act but I don't know. They were definitely not the driving force behind it though. Racism played a bigger role than the temperance movement. The government was also aware there was a very real problem with drug addiction.
> I see Europe eventually coming to this same conclusion when enough damage has been done.
I'm curious about this sentence -- to what are you referring, and where specifically in Europe?
Portugal decriminalize d all drugs a little while ago
And they have very low drug mortality rates. Opiates are prescribed _way_ less than in the US. This really feels like a strawman comparison.
Notice the word „decriminalize“, not „legalize“. It’s about not throwing people already struggling with addiction in jail but rather offering safe alternatives (counseling, safer use, etc.).
The government‘s not passing out drugs in the street, like US media likes to suggest.
Nowadays they're just given methadone or Buprenorphine (other opioids). Having known family members that worked in the clinic, there is no plan to get most of them off of it. It is like other opiate addicts, ~most of them take it until they are dead unless they are just dead set on getting off and willing to live with the fact they might never quite feel 'right' again, although at least it is safer.
Is that such a bad thing? Plenty of people will take medications for the rest of their life -- statins, antipsychotics, antidepressants, ADHD meds, antiretrovirals. The stigma of chronic medicine use needs to go away.
I don't know it's a bad thing, just pointing out, the US does just prescribe opiate addicts more opiates basically for life without a plan to stop it. Responding to "They put them on lists and prescribed them dope and it spiraled out of control ... metering out hard drugs has always been a road to ruin" with the facts that's what we're already doing writ large. The thing many people argue shouldn't become the case is already the case and many are oblivious to it (thinking that it was just a thing in the past we stopped).
It isn't the same drug as fentanyl, but it never really stopped being the plan that we will take people from 'the list' and just keep metering opiates out indefinitely. GGP posted this in a way that seemed to allude this was not currently the case.
If only there was anything different between 125 years ago and now!
People haven't changed
Can enforce sales limits with IDs and computers
Sr-17018 is making rounds now (ok was a year ago) among people using opiates too much. On forums, it is pushed as the miracle stuff which allows lowering dosage without major withdrawal.
It's fantastic, the main Iboga practitioner I work with now mainly works with SR.Its a much easier process. Imidazenil has also come to the scene at much cheaper prices for benzo withdrawals.
That's because the reasoning does go in circles.
0) Zero tolerance! We still remember how it ended last time!
1) But ... pain medication helps against anything. From headaches to hernia to bone cancer (of course in some cases it's in a "die somewhat dignified" sense). And in quite a few cases it's the only thing that helps ... In the medical sense of "helping", after all medicine can't make people live forever so that can't be the goal. The goal is better quality of life, ie. mostly longer life, including the ability to live (think "sing, dance and play tennis") ... and not life at any cost.
The problem here is that this is an entirely correct argument. Some diseases are either incredibly painful or long-term painful. Bone cancer or hernia can serve as examples. We cannot really help such people (by that I mean: not in a way that the pain stops). So can we at least make their life livable?
2) This pain medication sure helps these very seriously ill people well. But X suffering is at least as bad as bone cancer! X then is everything from still serious diseases, psychological suffering, and of course this then goes down and down until someone points out pain medication also helps existential dread and lackluster parties.
Again, all of that ... is true. That's not the problem.
3) The medication becomes the problem. Mostly because of what people do to get money for their fix (and the crime, prostitution, ... that it leads to). But this is not the only problem. It makes people who broke a bone last week go skiing again. And ... I'm almost afraid to say it but you can increase the effect of morphine ... by damaging yourself. You can guess how that ends.
The problem is that pain medication, irrespective of whether it's physically ("biologically") addictive is addictive. Anybody who's had a serious pain for a week, say kidney stones, knows that they would have sacrificed their favorite cat for it to stop. The problem is not just that morphine is addictive. The problem is the pain, and the fact that pain medication is a temporary non-fix.
4) The medication becomes the problem, but doesn't just affect patients. It goes from "you know this funny thing happened to my niece ... and she did it to herself ..." to it destroys families, neighborhoods, childhoods ...
Result: ONLY ONE SOLUTION! ZERO TOLERANCE!
GOTO 1.
Isn't the entire endgoal of studying medicine and biology to make humans live "closer to forever"? Aren't we working toward expanding human lifespan till we either hit a hard ceiling or approach infinity?
There is a nuance here. Sometimes, it is not "temporary bad solution" vs "trying to find better solutions", but "temporary bad solution" vs "suicide".
Aren't hernias usually repairable by surgery? Both of the folks I know who had them had a pretty quick recovery.
What the surgery actually does is fix 2 disks of your spinal column against each other. It lowers the pain from torture to tolerable and reduces various risks. Also: you won't be so much as sitting up for months. I don't think many people will call that repair. Perhaps mitigation.
I think you are both talking about slightly different things:
* Herniated disk in the spine * A "hernia": is the abnormal exit of tissue or an organ, such as the bowel, through the wall of the cavity in which it normally resides.[
That's called a "fistel" and it's a very serious condition, requires immediate surgery, and recognizable by the smell from roughly a kilometer away.
No, a fistula is different than a hernia.
If you think of your abdomen as a bag full of tubes, a fistula is a hole in the tube that connects to something else. A hernia is a hole in the bag, that the tube can poke through.
https://en.wikipedia.org/wiki/Hernia
Im guessing English isn't your first language? Fistel is not a commonly used term.
On the one hand, I'm sure that the post you're responding to is referencing many previous failed attempts at making non-addictive opioid painkillers.
But on the other, non-sarcastic side... if addiction is the only remaining problem with them, should we care that much?
I.E. if both the chronic and acute health risks are gone (which I don't think they are for a second, but follow me along on this little thought experiment)... does it matter quite so much? Clearly addiction, in the abstract, is not exactly a good thing. But if it's not coupled to risk of death it seems to me it would be a great thing to transition addicted people to, and take away some of the urgency of the situation.
I agree. I would say that I am addicted to caffeine. I definitely get withdrawal symptoms if I don't have a coffee. But since it is so accessible and there are no health risks, it does not affect me negatively to "feed" the addiction.
Not a great analogy. Caffeine is not as addictive as opioids. Opioids strongly stimulate the mesolimbic dopamine pathway, leading to intense euphoria, compulsive use, and severe health and social harm.
Tyler Cowen has said that he doesn't drink coffee and he is worried about what it might be doing to us. There is a big unknown.
I admit that I don't know who Tyler Cowen is, but millions (billions?) of people have drunk coffee daily for centuries and if there were ill effects in the same ballpark as opioids or tobacco by now we would certainly know?
There is even a decent chance that the Industrial Revolution and the phenomenal wealth and progress it's brought was caused by the introduction of coffee to Europe.
Hey, let’s not discount the opinion of some internet guy just because of the lived experience of the rest of humanity throughout history. /s
That's an attack on HN comments in general.
A professor of economics has opinions on the health effects of an extremely common substance?
And I have opinions on nuclear energy - but neither of us are worth listening to outside our areas of expertise. Unless you can supply a reason I would bother listening to him as compared to an actual expert on the subject?
Why should I care what an economist's opinion is on coffee consumption?
> There is a big unknown.
Because some dude with no health or nutrition background said uninformed things, that he isn't qualified to have opinions about, on the internet? Come on, now.
By definition addiction involves pursuing substances or engaging in behavior repeatedly despite negative consequences in one’s life.
Any behavior or substance that causes serious addiction is still bad regardless of whether it causes death or other negative health effects. The addiction itself inherently causes suffering because the addict is engaging in something despite the negative consequences in the rest of their lives. The negative consequences cause suffering and the psychological pain of wanting to stop and not being able to stop also causes suffering.
I know some other commenters mentioned caffeine addiction but nicotine and opioids (and also behavioral addictions like gambling) are vastly more addictive than caffeine.
Negative consequences from addiction can involve more than loss of money (although loss of money is still a significant thing of course.) They can cause damage to one’s career, family relationships, friend relationships and so on. Even if the addictive behavior or substance has no other inherent negative health effects.
In high school I had a really bright and motivated friend. He went to an Ivy League school. He became horribly addicted to World of Warcraft as a freshman. He spent so much time playing the game that he damaged his grades and GPA. He almost failed out of school. He had to make serious effort to stay in school. And he had to spend tremendous mental effort to avoid playing additive games anymore. That’s just one example.
> .. if addiction is the only remaining problem with them, should we care that much?
I think we should because it’s undignified to have people who want to stop taking them but are unable to resist the compulsion. I feel the same way about basically every addictive substance. Even if it was freely available and risk-free I still think that being trapped in a cycle of use and withdrawal is such an affront to someone’s dignity that we should still try to prevent that.
There's already buprenorphine and methadone. But, using either means some degree of responsibility, punctuality, etc. So unless you mean freely distributing it with very little process, it wouldn't change much.
Those, from what I understand, don’t hit the same and someone needs to be ready to quit to go on them, they help with withdrawal etc, definitely, but are not always successful as they don’t scratch the full itch. A bit like nicotine replacement therapy
But there’s a whole space of harm-reduction before then, which is where things like the Swiss program to provide heroin in controlled circumstances can fit in.
An opioid without respiratory depresses on problems could fit into that sort of thing pretty well.
> if addiction is the only remaining problem with them, should we care that much?
Have you _seen_ what the streets of major cities look like these days? Ever heard of "fent zombies"?
I’m in one now. The problem here is meth. But then I’m not in the US and things are different in different places.
It was a thought experiment about addiction if the other negatives could be removed, I doubt we’re actually anywhere close to that anyway, but it might imply that zombification had been solved.
I mean I guess it depends on the level of use? Do you need to be nodding off, drooling on the verge of respiratory collapse to cope with the dread of your situation? (I feel like people are mostly only considering the physical reasons for starting opiates in this post btw). Or is it a more reasonable dose that allows you to participate in society unencumbered by your pains? (Which in any case is a slippery slope with long term use)
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Ha, you won’t find me arguing addiction to meta products is harmless ;)
The chinese factories and cartels can hop on this new formula not.
and the fun fact, the other new drug targeting the mid-receptor of acetyl-choline that functions like mu-opioid receptor also has the same exact addiction problems.
>each of which ended up making a stronger, more dangerous opioid
This is true of some early opioids like heroin, but with e.g. Oxycontin the problem wasn’t a stronger opioid, it's how it ended up being prescribed.
Purdue's marketing led doctors to prescribe it to more people, in higher doses, and for longer. Oxycontin isn't inherently more dangerous than the dose of immediate release oxycodone or morphine that would have an equivalent effect.
Innovation in opioids shouldn't just be written off. They're still the best (and sometimes the only effective) treatment for a huge number of people, and some new opioids like buprenorphine/combos like Suboxone have real advantages.
The lesson from Oxycontin is more about deceptive marketing and prescribing practices.
I mean if there were no safe dose or usage pattern then I would expect a lot of mothers to leave the hospital with both a newborn and a crippling addiction. The epidural is an opiate like fentanyl.
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Adjacent medicines have seen major improvements: eg Ketamine was a significant improvement from PCP (notably, less psychosis and safe enough to use off the battlefield / with children)
“Removing the worst and most fatal danger” is a laudable goal with Fentanyl given the absurd rate of ODs
As have the opioids buprenorphine and Suboxone (buprenorphine/naloxone), which are genuinely useful treatments for addiction and have much lower risks of abuse.
No, same. Reading the headline, I immediately thought "Aw shit, here we go again".
It's like that xkcd comic about unifying standards, now we have n+1 addictive opioids.
We really could use better treatments for chronic pain.
I've found low dose naltrexone to be somewhat effective for severe chronic pain. Not as good as opiods.
THC can also help somewhat, but its action seems so dissociative. At an effective level for chronic pain, I'm sleepwalking though the day.
Opioids or their analogues cause or complicate bowel issues. Four years of 200mg/day Tramadol really helped me, but it shredded my gut. Getting off Tramadol wasn't hard for me. I'd stay on it were it not for the gut issues.
As an aside, lacing hydrocodone with acetaminophen is truly a horrific practice. Doctors prescribe this to patients on hepotoxic drugs and are shocked when they get liver damage.
I have 2 family members for whom Tramadol opened the door for severe addiction. One is now on regular morphine, the other had psychosis. I know it obvisouly depends on the individual, just to dilute your very rosy comment
I didn't mean to make a rosy comment, thanks for the ribbing.
Tramadol isn't all that strong, but it does take the edge off. With a 6 week taper, my challenge was more about the resurgent pain.
I would not recommend Tramadol, the gut complications are debilitating and it's unclear ignoring the chronic pain served me well.
Right. Opioids are an absolute terror to one's digestive system. When I had chronic pain I would rather have just accepted the pain than deal with the gut consequences.
LDN is an interesting one since it just stimulates your body to generate its own endorphins.
I found the first week on LDN to be challenging due to "horror flick" vivid dreams.
LDN reduces "central amplification" of neuropathic pain, so it is a good fit for my disease profile.
LDN is interesting since what it does is actually trains your nerves and brain to feel more pain… so they get used to it.
> I've found low dose naltrexone to be somewhat effective for severe chronic pain. Not as good as opiods.
When I could get 7oh, it worked well for moderate break-thru (ibuprofen) pain (muscle, joint). I also tried a month of using it regularly wasn't happy overall. I didn't get any withdrawal on stopping tho.
Have you tried pairing THC with a coffee? This is my go to for pain relief without being overly sedated.
Tramadol is cookies in comparsion to Fentanyl
Is fentanyl even that big of an issue in a clinical setting? It's not like it's the go to opiate of choice for general pain anyway.
The problem with fentanyl is that it is easy to make and smuggle and we managed to leave a giant black market hole to be filled when we went ape shit about oxy, which was an objectively better situation than we are currently in with street opiates.
Yes, it is an issue.
One of the big problems with anesthesia is balancing respiratory depression while medicating the patient enough to manage the symptoms. Fentanyl is used in anesthesia and it causes respiratory depression.
A strong pain medication that doesn't slow or stop breathing would significantly improve the safety of anesthesia.
It's a weird framing. Fentanyl is already very safe in a healthcare setting. It's only dangerous in off-label street use, where dosage is uncontrolled and use isn't being monitored by trained staff. Do we think cartel labs are going to switch to a safer novel opiate? I'm sure they don't care about any relevant patents, but they already have a pipeline/formulation for fentanyl.
They might, if it kept their customers coming back. They don't care about users' safety but they do want them to keep paying.
As a recurring kidney stone sufferer I am very thankful for fentanyl for my lithotripsy procedures. I hope we continue to make progress on effective pain medications and don't knee-jerk take them away.
This really should be a national priority on the level of cancer or HIV research.
If we got some safer painkillers that weren't insanely addictive, that would be Nobel Prize-worthy, in my layman's opinion.
Well, if it doesn't suppress breathing dangerously, and yet works on "pain" effectively, it would be the most widely abused drug on the planet...
People are going to abuse drugs. Making them less deadly is only a good thing, unless you want more dead addicts.
A lot of people do want more dead addicts. They think it's some kind of moral purity test.
I don't understand the scare quotes. Do you think pain doesn't exist? Do you think pain shouldn't be treated?
What is it you're actually trying to say without having to say it?
I have several naloxone kits in my house and my kids carry them in their backpacks. I'm pro harm-reduction.
With that in mind, what I'm "actually trying to say" is that
a) any time we can make a medication less harmful, that's a good thing; and,
b) if this new molecule relieves pain as well as fentanyl does, it will surely be used by people who are addicted to drugs or who are using drugs recreationally.
The bigger question that goes way beyond the scope of Scripps' research contribution is whether our society can begin to accept that people use drugs like fentanyl to treat depression, trauma, anxiety, and pain of all sorts. And that criminalizing their efforts to treat themselves does not lead to any improvement in their wellbeing or the wellbeing of our society.
Kind of fucked up you make your kids carry naloxone.
I don’t make them do that. They do it because they want to be ready to help in the seconds that matter if someone has an overdose. This is the sad reality they inhabit.
I wonder if this modification brings it closer to the mitragynine from kratom, which has opiate like pain dulling effects with very minor or no effect on breathing.
I hope so because the administration is looking to really fuck over medical research by making the 7-OH stuff a schedule 1 narcotic, when it has so much potential for improving anesthesia and pain management by removing respiratory depression from the pain killing element of the anesthetic cocktail.
My understanding is that mitragynine is an mu-opioid partial agonist which limits its impact even in high doses. This is sort of in the same realm as Buprenorphine. Google claims it also doesn't recruit beta-arrestin but admittedly I'm out of my depth here. Presumably this proposed fentanyl replacement is still a full mu-opioid agonist for efficacy.
Except even as the press release states right off the bat, Fentanyl is efficacious, cost-efficient, and can be made widely available in areas like the global south without extensive pharmaceutical production infrastructure in place. The overdose crisis is in fact not really something that came out of the drug itself, just as the prevalence of Oxycodone before the enforced policy change shifted the usage patterns into a far more dangerous direction in heroin and tar and then, adulterated versions with fentanyl. People who are prescribed fentanyl for pain are not dying in droves. If you've had surgery, you may have been given fentanyl. If you're reading this, you, like most people, survived it just fine.
The crisis is one created by policy and cannot be eliminated on the pharmaceutical end. This isn't a case of methanol being sold as ethanol or SSRIs having less than ideal efficacy rates while causing widespread sexual dysfunction at a rate much higher than originally thought, or Zolpidem leading to over a hundred observational notes published in medical journals describing dangerous activity performed even on small doses followed by anterograde amnesia that certainly is a real thing that is also potentially dangerous, but incredibly difficult to study. Those effects are happening when the medication is taken as prescribed Do people take those without prescriptions? Of course, but one assumes the risk, and also, anyone ever seen a Zoloft pill mill?
Fentanyl had been diverted in small quantities onto black market supply chains for as long as it has been available. You can absolutely get an Actiq Pop in 2006 if you really wanted it, and the thing is a lollipop for crying out loud. It didn't cause widespread overdoses, it didn't even cause any significant black market demand. It was at best a curiosity. It's hard to quantify a subjective experience, but generally it was regarded as "not fun" anecdotally. Heroin is fun. Hydromorphone is even more fun but the best ROA leaves you with a 5-10 minute high at best and takes about that much time to prep. Oxycodone was fun but since the DEA made sure that it was as difficult to obtain as possible all of a sudden and what was available was spiked with enough APAP so that your liver might give out before you overdosed, well, what does cutting off the supply but leaving the demand in place do? The crisis as we know it today was inevitable in some form. It's created by policy, which is not set by scientists, and in fact when hydrocodone/APAP was rescheduled for Schedule II a specific reply to patient access concerns was "we don't take that into account", according to the DEA. Thanks for the candor, sadly we've gotten very little of it in the years since.
But of course, even on the black market, people overdose in a manner that is to a degree predictable. Long term users with steady supplies - say, everyone who's on a benzodiazepine long term - aren't overdosing regularly (yes, the LD50 of benzodiazepines generally makes overdosing on it alone very difficult if not impossible, but kicking it cold turkey does actually cause deaths from seizures and when mixed with another depressant like alcohol it becomes almost trivial to overdose on it, arguably making it at least in theory a more dangerous drug if one takes the view of the DEA). They are mostly able to obtain legitimate, low cost, and frequently entirely legal versions of, well, name the variety. From Triazolam (3 hour half life) to Midazolam (water soluble) to Etizolam (scheduled into schedule I based on 4 cases in Norway where when mixed with another depressant patients ended up in the ER. All survived and were discharged almost immediately. The reason why the DEA laundered cases in Norway through the FDA to justify at first an emergency scheduling and then turned it into a permanent one? Because they couldn't find any cases that demonstrated the purported danger in the US or Canada.) Overdoses happen when someone takes too much of a substance, but "too much" is difficult to determine when you don't have a reliable supplier in terms of quality and adulteration, but also, because tolerance gets built up so that long term users can use prodigious amounts and be just fine. But how do we make sure that nobody knows where their tolerance is at? Non-medically assisted, pseudoscientific "sobriety help" like AA or its variants that are ordered by the court, and of course, probation, testing, in-patient medicaid fraud mills, you name it. Since none of these actually do anything except use homebrewed aversion therapy or even less efficient, shame, to achieve what is basically not even a real goal but is tied to the criminal justice system, congrats, you have the perfect storm of demand not knowing how much to actually demand for. Fentanyl being the adulterant made this last inevitable easier, but it only hastened what had been happening for quite some time. When heroin supply on streets increased, fentanyl related deaths began decreasing. Wonder why? It's correlative, but observational studies take a lot more data and a lot longer time periods, although it would certainly follow previously observed patterns.
This may be interesting as a scientific venture, but treating it as anything but that is foolhardy and misguided. We know how to control pain. We know how to reduce the harmful externalities that form part of the definition of substance use disorder since we, as in society and lawmakers elected by us, are responsible for those harmful externalities in the first place. Fentanyl is not the problem. Making sure that there's no safe way to reduce potential harm associated with, ultimately, a personal choice favored by some but certainly not all as recreation, killed the hundreds of thousands since Lou Reed sang Heroin and put it onto the Velvet Underground and Nico. Why are we still acting brand new?
I’ve been to a few AA meetings when I was trying to get my mom sober and I never got the vibe that it was about “aversion therapy” for alcohol. The whole point seemed to be to discharge your egotistical need to be “in control” of the alcohol and accept that it was taking over your life despite your best efforts. You were then supposed to seek help from the people in the group to try to keep that from happening. There wasn’t really a culture of shame but rather acceptance there. And they also pushed a lot of ideas like repair after rupture that are a part of normal human relationships. So I don’t really buy what you’re saying here.
bot post
Perhaps not. I checked his post history, and back in 2021, there are comments as verbose as this one (e.g. https://news.ycombinator.com/item?id=29180977).
I mean that is great. But the overuse of opioids in Us is crazy. I am from europe, had broken arm, sprained ankles, broken fingers, root canals done, appendix operation and never got anything stronger than ibuprofen. Hopefully, the prescription craziness is getting better.
Over the last 10 years, state medical boards have dramatically cut back on opioid prescriptions (which happens to correlate with the rise of fentanyl use). Even those with chronic pain with a history of prescription were cut back. It's unfortunate because for some people, opioids really are the only thing that works for treating incurable pain but the downside is that they develop tolerances and they become ineffective over time. It really would be a miracle if we could invent a pain medication that is non-addictive.
However, a new type of pain medication doesn't remove the current opioids available on the street. Legalization of marijuana is one thing, it's relatively low risk but I don't see legalization of opioids ever happening because absolutely nothing can replace the warm blanket feeling that they provide.
It's been cut back pretty hard in the last 5 or so years? Even after major surgeries you get very short prescriptions, or only get them in the hospital under monitoring. I think we got a little too cautious personally but it's definitely trying to swing the curve away.
They're not going to prescribe anything serious for those conditions in the US, either. You might get as much as codeine with acetaminophen. But there's a good chance you'll get nothing more than ibuprofen and local anesthesics.
damn! you gotta be more careful with your body.