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Fentanyl makeover: Core structural redesign could lead to safer pain medications
- bheadmaster 8mo agoFinally! 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.
- ViktorRay 8mo agoThe 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.
- fredgrott 8mo agoand 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.
- Nursie 8mo agoOn 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.
- tim-kt 8mo agoI 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.
- cactusplant7374 8mo agoTyler 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.
- Kurtz79 8mo agoI 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?
- donkey_brains 8mo agoHey, let’s not discount the opinion of some internet guy just because of the lived experience of the rest of humanity throughout history. /s
- cactusplant7374 8mo agoThat's an attack on HN comments in general.
- BurningFrog 8mo agoThere 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.
- switchbak 8mo agoA 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?
- wongarsu 8mo agoNot 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
- monero-xmr 8mo agoTo 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
- cluckindan 8mo agoMost 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.
- alphawhisky 8mo agoThis cuts to one of the more important points here. Rent seeking behavior in public health is crazy to witness.
- apothegm 8mo agoDon’t forget for-profit prisons!
- tokai 8mo agoIt'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.
- kvgr 8mo agoThe chinese factories and cartels can hop on this new formula not.
- bena 8mo agoNo, 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.
- DesaiAshu 8mo agoAdjacent 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
- at-w 8mo agoAs have the opioids buprenorphine and Suboxone (buprenorphine/naloxone), which are genuinely useful treatments for addiction and have much lower risks of abuse.
- at-w 8mo ago>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.
- goolz 8mo ago[dead]
- throwaway173738 8mo agoI 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.
- deleted 8mo ago[deleted]
- kvgr 8mo agoI 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.
- nemomarx 8mo agoIt'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.
- deepriverfish 8mo agodamn! you gotta be more careful with your body.
- wildzzz 8mo agoOver 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.
- jfengel 8mo agoThey'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.
- jimz 8mo agoExcept 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?
- clcaev 8mo agoWe 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.
- dgan 8mo agoI 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
- clcaev 8mo agoI 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.
- iberator 8mo agoTramadol is cookies in comparsion to Fentanyl
- trollbridge 8mo agoRight. 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.
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- leetrout 8mo agoAs 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.
- jfyi 8mo agoIs 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.
- droopyEyelids 8mo agoYes, 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.
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- ttul 8mo agoWell, if it doesn't suppress breathing dangerously, and yet works on "pain" effectively, it would be the most widely abused drug on the planet...
- jmye 8mo agoI 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?
- ttul 8mo agoI 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.
- ThrowawayTestr 8mo agoKind of fucked up you make your kids carry naloxone.
- ttul 8mo agoI 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.
- ThrowawayTestr 8mo agoPeople are going to abuse drugs. Making them less deadly is only a good thing, unless you want more dead addicts.
- lenerdenator 8mo agoThis 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.
- loeg 8mo agoIt'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.
- jfengel 8mo agoThey might, if it kept their customers coming back. They don't care about users' safety but they do want them to keep paying.
- droopyEyelids 8mo agoI 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.
- loeg 8mo agoMy 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.