Black mamba venom is 'better painkiller' than morphine (2012) | Hacker News Reader

Black mamba venom is 'better painkiller' than morphine (2012)

bbc.com

90 pointsScottMann87 comments

There is a lot of research aiming to produce strong, non-opioid pain killers from venom peptides, from spiders, centipedes, sea anemones and other creatures.

These peptides have an action on sodium channels, specifically Nav1.7, so the article doesn't seem particularly surprising (although the article was from 2012, so it might have been back then).

We already have several drugs that work on sodium channels, but they are non-selective, and there are several sub-types of sodium channel with different uses - such as regulating heart beat. The challenge, is to produce a drug that selectively blocks sodium channel Nav1.7 - the idea being that this will reduce pain while not affecting your heart etc.

I suffer from chronic neuropathic pain, so I've been somewhat following this research for a while.

A similar venom-based analgesic that actually became a drug is Ziconotide [0], a selective calcium channel blocker contained in a certain type of cone snail venom (the actual drug has some minor modifications for stability but the structure was already perfect re: activity). Unfortunately as a peptide it's not orally active and has to be administered directly into cerebrospinal fluid.

I only know about it because the person who discovered it gave a wonderful talk at my grad school. Apparently venomous sea snails produce incredibly diverse mixtures of incredibly receptor-selective peptides. They used a cheap phenotypic screen in which snails were purchased from fishermen, venom fractionated by HPLC, individual fractions injected into mice, behaviors were characterized and interesting ones flagged for further study.

[0] https://en.m.wikipedia.org/wiki/Ziconotide

FTA: They admit to being completely baffled about why the mamba would produce it.

I would guess it keeps their target calm. A panicking prey is more likely to injure the snake than one that dies before it realizes it got seriously bitten.

>> FTA: They admit to being completely baffled about why the mamba would produce it.

It's because they are scientists. Scientists are always "baffled", in the news.

Very frustrating. In practice the scientists are expressing uncertainty “we do no know/need to investigate further” not confusion or bewilderment

I can imagine the journalists asking them "are you completely baffled?".

"the mind that is not baffled is not employed

the impeded stream is the one that sings"

-- Wendell Berry

That’s a simple and lovely poem that speaks to me deeply. Thanks for teaching me it exists.

A snake, you see, Has no legs to flee. When frightened He does not dither, He slithers.

(high school poet me, neither lovely nor deep, but I can't help myself)

Berry's a good well for deep-speaking thought.

The essay from which it comes is pretty great too -- I don't think it's online in whole form but there are pieces discussed here:

https://www.brainpickings.org/2014/11/18/wendell-berry-poetr...

Yeah for real this is a major issue in news and science communication.

There's "we don't know" (and we have no idea why), there's "we don't know" (just because we didn't prove it yet, but our money is on that) or (we think it's because so and so but haven't looked into it) and in-betweens.

> being completely baffled about why the mamba would produce it

Is it delivered in a dose sufficient to cause unconsciousness, or even just euphoric lethargy in its prey? If so, that sounds both effective and weirdly sweet, given nature's usual barbarism.

I am continually frustrated by and fail to understand how people can actually believe nature is barbaric. Nature is nature, it is kill or be killed, that is actually the natural order of things.

Outside of that is an anomaly reserved for those at the absolute apex of power. This power was accumulated by being incredibly adaptable and observant. Both of these qualities made our ancestors very very good at killing things.

> frustrated by and fail to understand how people can actually believe nature is barbaric. Nature is nature, it is kill or be killed, that is actually the natural order of things.

Barbaric literally means primitive and unsophisticated. (Sophistication referring to knowledge and culture.) When we say something is barbaric, we mean it is in its natural, unrefined, untouched-by-civilisation state.

That might make the statement "nature is barbaric" seem tautologic. But your reaction exposes its meaning. The natural state of things, the barbaric state, is on we strive to escape. It is painful and suffering. Sometimes cruel. Enough to have motivated our species to seek to not be subject to it. To be free of the "natural order of things" by developing our knowledge, culture and civilization.

As you mention, this often involved killing. But killing need not be painful and cruel.

> Barbaric literally means primitive and unsophisticated

This makes for the foundation of a nice story, but no, that's not what 'barbaric' means. It's not what you'll find in any dictionary, and it's not what the root of the word is. Barbaros, in Greek, referred to non-Greeks, with an early connotation of foreignness. It picked up a connotation of cruelty and savageness as early as the Romans. Any dictionary since then will give a primary meaning of cruelty and savagery, not just 'primitive and unsophisticated'.

(Finally, my eight years of Ancient Greek at school comes in slightly handy!)

> Any dictionary since then will give a primary meaning of cruelty and savagery, not just 'primitive and unsophisticated'

And how would those dictionaries define savagery? Webster's first entries are "not domesticated or under human control" and "lacking the restraints normal to civilized human beings" [1]. The penultimate comment works with savage and cruel substituted for primitive and unsophisticated.

(Though didn't know the etymology. An honest thank you for that.)

[1] https://www.merriam-webster.com/dictionary/savage

> And how would those dictionaries define savagery?

I mean, a good nothing-up-my-sleeve definition is the Google one: https://www.google.com/search?q=define+savagery https://www.google.com/search?q=define+savage

Respectfully, I think you're hunting down odd-one-out definitions that support your theory - not necessarily consciously. All of these words connote cruelty. The overwhelming majority of dictionary definitions bear that out.

I don't think arguing about the semantics of "barbarism" really takes away from the original overarching argument: nature is primitive and cruel but humans in general at least try to alleviate that kind of cruelty seen in non-human nature.

> takes away from the original overarching argument: nature is primitive and cruel but humans in general at least try to alleviate that kind of cruelty seen in non-human nature

And if that were the only claim they made, that would be fine. I just happen to dislike people dishonestly twisting facts – in this case, misrepresenting the meaning of a word by cherry-picking some recherché fringe definition and making it out to be the primary meaning – to make their argument sound more impressive.

> a good nothing-up-my-sleeve definition is the Google one

Now try “barbaric”. Definition two: “primitive; unsophisticated” [1]. (Sorry, could not help it.)

> these words connote cruelty

Never argued it didn’t. My original comment uses the same word.

[1] https://www.google.com/search?hl=en&q=define%20barbaric#crs=...

> Now try “barbaric”. Definition two: “primitive; unsophisticated”

Yes, definition two. I reiterate what I said before: you're searching for fringe meanings to back up your argument.

Your original comment argued that the meaning of 'barbaric' was primarily about simplicity and primitiveness, in order to argue that the phrase 'nature is barbaric' is agnostic about nature's cruelty. This makes for a neat-sounding argument, but, again, it's unfortunately just not true. The word 'barbaric' has signified cruelty as its dominant meaning ever since the Romans.

(I know it's tempting to twist the facts a little to make an elegant argument, but it's just not honest to cherry-pick secondary definitions, or anomalous definitions from minor dictionaries, and use sleight-of-hand to pretend that's the main understood meaning.)

> When we say something is barbaric, we mean it is in its natural, unrefined, untouched-by-civilisation state.

No we don't. We generally use barbaric to describe people. Barbaric comes from barbarian. Which was originally used to describe non-greeks, non-romans, foreigners, etc. It started out as a slur. Philistine is a synonym for barbarian.

https://www.etymonline.com/word/barbarian

> Enough to have motivated our species to seek to not be subject to it.

You act like civilization was something our species strived for rather than had imposed on us. Civilization was predominantly built on slavery and exploitation. The vast majority of humanity suffered under civilization. Humanity no more clamored for civilization than livestock clamored for industrial farms.

Yup, you're entirely correct. I'm disappointed to see your point downvoted. I thought HN was above believing in arguments just because of their elegance, even if that elegance is accomplished by distorting the facts.

> I am continually frustrated by and fail to understand how people can actually believe nature is barbaric.

Because it is.

> Nature is nature, it is kill or be killed, that is actually the natural order of things.

That’s also what people describe as “barbarism”, generally. So, you seem to agree that nature is substantively barbaric, but be confused that people describe it that way.

Very aptly put.

I would guess it's just a genetic glitch and not some conscious decision or purposeful design.

It doesn't have to be a conscious decision or purposeful design to be "there for a reason". Evolution tends toward solutions because the population that happens to be closer to a solution are more likely to survive. Nothing the op said was incompatible with evolution.

In addition to that, it's certainly not a 'glitch'. A genetic glitch would be a (possibly short-lived) mutation which is still in the 'beta' phase, so to speak, or else a harmful side effect of an otherwise beneficial mutation (e.g. albinism). This is a paradigmatic example of an ordinary useful mutation which persisted because it increased fitness.

Evolution doesn't have "reasons" (pre hoc is random mutation) but it has "justifications" (post hoc is natural selection).

I would much rather tend a field of poppies than a mamba snake ranch. Poppies hardly ever run away from thunderstorms.

On one side, this is an incredible medical advancement and opens the door to a lot of other developments, but on the other side if my doctor said I was getting injected with snake venom...

Your doctor wouldn’t say that. Your doctor would prescribe you polylepiscin or some other vaguelly medical and scientifical sounding name. You wouldn’t know that the compound originally was found in black mamba venom unless you like geeking out on medicine history. (And if you like geeking out on that you would already know that nearly all drugs comes from weird things.)

Yes exactly. Bacteria in probiotic yoghurt come in from the guts... no one says “fancy like eating your own shit”?

In fairness, the U.K. adverts for probiotic yoghurts have said it contains natural bacteria found in the gut.

Thank you for reminding me that fecal transplants are a thing and have shown real world benefits. The one time a suppository is preferable to oral administration.

I do enjoy geeking out over medical things in general and would trust that an approved pain killer would not be straight up venom and will happily take it, especially if it lives up to the hype. I'm still going to give any doctor that prescribes it to me just a little bit of grief, though.

Wait till you find what we use salmon sperm for

I’ll see your salmon sperm and raise you one penis facial[1], as recommended by Sandra Bullock and Cate Blanchett.

Few people seem to care that the source of the active ingredient in the penis facial is obtained through the egregious action of cutting healthy, valuable tissue off of male Korean infants who have no diagnosis of defect or disease.

[1] https://nypost.com/2018/03/15/the-penis-facial-is-the-latest...

Like Botox. The doctor doesn’t mention they’re injecting you with botulism (or maybe the toxin that causes botulism?) but they are.

The very common ACE inhibitor medications for high blood pressure (lisinopril and the others that end in -pril) are synthetic analogs of a compound found in the South American pit viper Bothrops jararaca. Scientists noted that being bitten by one of these snakes produces a rapid and profound drop in blood pressure. In the wild, of course, this causes the snake's natural prey animals to pass out so they can be eaten.

So it's not like snake venom-related drugs are unprecedented.

Any experts on here know whether it'd be possible to create a synthetic version? It would've expected that issue to be mentioned in the article tbh

I could spray paint a garter snake for ya, would that do?

(sorry)

Venoms are often a bitch because they're not stable, I think. manufactured at point of use for a good reason.

That's interesting thanks, I suppose that's why we've not heard anything about this discovery since

The title is not good--lots of meds are betting than morphine...that's why we have all the other opioids: hydromorphone, fentanyl, remifentinil, sufentinil, oxycododone, etc.

If you look at the Nature abstract linked from the news article, all they claim there is that the analgesic effects can be, "as strong as morphine."

This also a protein which is inherently more expensive and difficult to turn into a drug compared with a small molecule.

Also diamorphine (heroine), which has several advantages over morphine and is used medically outside the USA.

Yup, it's used widely in end-of-life care here in the UK (I remember my mum once saying to me, when we were discussing euthanasia, that there's no doctor in the country who hasn't 'accidentally' given a little too much diamorphine to someone who was on the verge of death and in pain).

It's useful, but I imagine it's tainted in the US by the association with street heroin - somewhat curiously, since fentanyl apparently hasn't been tainted by its recreational associations.

I've no idea how often it is done with the intent to end life, but doctors are legally allowed to give doses of medication that may hasten death, providing their intention is only to relieve pain and suffering - https://en.wikipedia.org/wiki/R_v_Adams_(1957)

It can be argued[1] that only doses that are virtually certain to cause death lead to liability for the death, so no doubt there is some overlap between doses given to relieve pain and those that quicken death.

Diamorphine is also sometimes used for labour pain.[2]

[1] https://www.uhs.nhs.uk/HealthProfessionals/Clinical-law-upda...

[2] https://www.nhs.uk/pregnancy/labour-and-birth/what-happens/p...

Indeed, you're referring to the doctrine of double effect (which the linked Wikipedia article on R v Adams mentions).

That said, I don't think "[only] doses that are virtually certain to cause death lead to liability for the death" is correct. You had it right the first time: the relevant fact is not whether it's likely or even certain to cause death, but rather whether causing death is the primary intention. (I'm not a lawyer, though, I'm just speaking on the basis of my knowledge as a lay person.)

For a popular magazine that seems fine... analgesic as strong as morphine + fewer side effects = better overall ... no?

It's hard to know what the side effects are since it hasn't been tested in humans and is not in a form where it would be a useful drug. We've had plently of promising drugs turn out to have unexpected and sometimes devestating side effects when tested in humans.

It's fine, morphine is used as a 'standard' for opiate and other pain killer efficacy. So often that the term 'morphine equivalency' exists in medical documents.

Those drugs aren't better, in my experience, as a chronic pain patient. Morphine is way less addictive, longer lasting, with fewer side effects. Not to mention, it's natural, one of the main alkaloids from poppy. Now, I'm not a dolt who thinks natural is better. However, most synthetics are strictly worse from a therapeutic standpoint. This view is based on my experience with them and from my discussions with other patients. From what I understand, the synthetics are pushed on patients for incentives. I had to pretty much demand morphine instead of oxy. Thanks Sackler family!

Morphine XR (MSCont) is also pushed instead of normal morphine, again, I think for similar reasons. Although on the surface, it might seem like an XR would be helpful. Instead it just causes more constipation and doesn't give a great absorption profile.

Morphine IR 30mgs taken throughout the day pretty much vaniquished my pain. These days though, I use Kratom, Mitragyna Speciosa. It's as effective as morphine with less side effects. I also try to work out every day. Having strong muscles in the painful areas seems to help with the pain, either due to increased blood flow or perhaps for other reasons.

Nucynta (Tapentadol) was the most effective synthetic opioid I ever used but without insurance it cost me $3000 a bottle. Kratom is cheap as dirt even without insurance. $70-80 buys 1 kilo / 2.5 pounds of the ground up leaf. I have enough kratom in my cabinets to last a covid apocalypse.

You can get lab tested Kratom that is cGMP certified these days. I have nothing to gain by providing this information, just happy I found a pain reliever that is sustainable and doesn't require talking to a doctor playing a drug pusher every month.

Lots of people have had bad experiences with kratom giving them headaches/nausea. This is largely due to poor quality kratom from head-shops and gas stations or from consuming excessive doses. Never buy Kratom that isn't lab tested with GC/MS. And don't take too much of any opioid unless you want motion sickness.

Surprised this comment is rather downvoted. This view isn't uncommon among pain patients-- such alternatives to opioids are being researched and an article like this appears every so often, but the miracle hasn't panned out. Ziconotide, based on a toxin from a sea snail, is one of the few that have made it through the development process but is still extremely specialized. While it's 1000 times as strong as morphine and non- addictive, there are other considerations with such drugs. Dosing intravenously can cause extremely strong side effects, so the drug is dosed through a pump in the body directly into the spinal fluid. Obviously such an implant must be surgically installed into the patients spine first, which comes with risks of its own. The drug also can cause extreme neurological side effects such as hallucinations, delusions, and suicidal thoughts. For this reason it's contraindicated in those with a history of psychosis, bipolar disorder, or depression. For all these reasons, though it's available it's used as a drug of last resort. Oh and it's quite expensive as well, so it effectively is only available to those who can afford expensive medical treatments. Unfortunately it will still be some time before there are viable alternatives for moderate to severe pain

Fascinating peptide, and from snail toxins, amazing, thank you for illuminating it. Apparently metabolism isn't the issue for oral use of Ziconotide, the blood brain barrier is. Researchers are currently working on using viral nanocontainers to transport it past the BBB [1] so that it can be taken less invasively. I find it fascinating that it works on blocking voltage-dependent calcium channels [2], not by agonizing opioid receptors.

It intrigues me that so many natural venoms, toxins, and poisons have analgesic agents as part of their chemistry. What do you think the reason for this is? Would a prey that doesn't realize it is in pain, perhaps struggle and flee less? If this is the case, shouldn't some of these predators have evolved to have pleasurable agents like opioids in their toxins? I suppose it might be hard for their own body to not be affected by it though? I'm gonna have to look into this topic some more. It's really fascinating to see divergent evolution hitting the same motifs.

I'm used to being downvoted, and even flagged. I say things that are deemed too controversial for the average automaton that inhabits HN. Not much can be done, so I've just come to embrace the hate. I'm not a troll but in order to deal with the constant attacks against the truth, one has to develop thick skin and perhaps even some enjoyment over knowing that people are so disturbed and shaken by foreign facts that they instinctively try to bury the newfound knowledge. Such is humanity, and HN has been growing and becoming more and more averse to truth. I hope it does not tip too far, but if it does I'm sure another community will fill the void. All we can do is speak our peace and live to fight another day.

[1] https://www.nature.com/articles/srep12497

[2] https://en.m.wikipedia.org/wiki/Conotoxin

I've read that that stuff is bad for your liver. Worth keeping an eye out for signs of jaundice.

https://en.wikipedia.org/wiki/Mitragyna_speciosa#Liver_toxic...

Thank you. Most of that, like plant protein powders, is due to heavy metals in the soil the plant is grown in, or adulterants. I've been using Kratom for over 5 years with no elevated liver enzymes. It's actually made me healthier since it, like other dark green leafy vegetables, has many micronutrients and minerals.

NEVER buy kratom from a gas station or head-shop. That's likely where most of incidents stem from.

To anyone reading this: please ignore what this person is saying. Addicts will rationalise everything, and blame every negative side-effect on 'adulterants' or 'low-quality supply' or other varieties of 'stuff I would never do myself, compared to my perfect and healthful regimen'. Kratom is not good for you.

It's easy to pass judgement.

>Kratom is not good for you

Few effective painkiller are. Ibuprofen causes stomach bleeding, acetaminophen has toxic effects on the liver, prescription opiates are even more addictive than Kratom while running the risk of overdose. Ziconotide, what was supposed to be a miracle drug made from sea snail venom requires an invasive body implant to dose directly, and in long term use has a habit of causing suicide and psychosis. In fact it's a drug of last resort. Kratom has some health concerns but it can and is used as pain management in some people. This thread is full of people complaining it wasn't fun or felt strange-- missing the point which is that the point is pain relief is hard to come by

It's easy to pass judgement.

>Kratom is not good for you

My point isn't that it "isn't fun or felt strange". My point is that it's dangerous and addictive. It's not honest to equate it to the minor hepatotoxicity of over-the-counter NSAID painkillers. Ibuprofen does not have a 25-thousand-member subreddit for addicts trying to quit (https://www.reddit.com/r/quittingkratom/).

Fair. Therapeutically, it's a pain killer, plain and simple. When people look for more in ANY medication, then they usually start to abuse it and dependency develops. Abuse can be as simple as overuse. I'd consider taking any psychoactive drug daily to be overuse.

Patients have dependency issues with opioids, anti-anxiety drugs like benzodiazepines, or with ADD drugs like amphetamines, modafinil, or phenidates. Even antidepressants like SSRIs have extreme dependency and withdrawal which patients are often not informed of. That's why I'm focusing on dependency, not psychological addiction. Mental fortitude can usually defend against psychological addiction - but dependency on the other hand, is purely physical and a function of the dosing regimen and properties of the drug.

Many patients use the aforementioned drugs responsibly for decades. It's not too far from the case of drinking problems. If one fills a void in their life with alcohol, they'll end up addicted. If a businessman imbibes alcohol occasionally before speeches as a relaxant, without becoming overly reliant on it, they won't develop dependency or addiction.

Being an addict has probably scorned you regarding the therapeutic nature of neuroactive chemicals. And that may be for your best.

I agree, most people are too weak to take even a mildly addictive narcotic like morphine or xanax. But kratom is not in the same league. And it is a joke to taper off of. I've done it multiple times before.

Any street drugs are going to be of dubious physical effect, and cause confusing withdrawal symptoms as they are often inaccurate, impure, or adulterated. Do you think a large majority of /r/quittingkratom knows what's in their kratom - did they buy lab tested product? Most are buying from local shops without any understanding that everything we put in our bodies should be of stringent quality and purity.

Half of the subreddit could be withdrawing from Fentanyl without even knowing, while putting all their blame for their horrible withdrawal symptoms on kratom. The unregulated market severely distorts public knowledge of the plant's real properties.

May I ask, did you ever take prescription morphine? Did you get your kratom from a cGMP lab-testing vendor that publicly releases labs? If not, your experiences with these chemicals may in actuality be experiences with other chemicals.

Anyhow, you seem extremely in opposition to the notion of responsible medicating so it's doubtful you will have a discussion with me. But in the case you do, I appreciate it.

I'm happy to have a discussion if you're willing to accept that kratom is addictive.

Suggesting that the 25k kratom addicts on that subreddit all took fentanyl-laced kratom, and kratom itself is absolutely non-addictive, is delusional nonsense which I'm not going to engage with.

If you want to engage on the basis of reality, I'm very happy to chat. I think you'll find I'm a hell of a lot more open to healthy opioid use than 99% of the people you'll find on this planet, but I'm not going to enable you in your delusions.

I don't deny it being addictive. It's just not as addictive as the prescription opioids. I'm sure a lot of those users on /r/quittingkratom just took too much of it and dug a hole too deep. What exactly do you hope to accomplish here? I am not telling people to do kratom for fun. All I really stated was that it's a good alternative to prescription painkillers. Which I really do believe based on my own experience as a pre-med student and as a chronic pain patient myself.

It's a pain relieving plant. You got problems mate. Go to the nearest pain clinic and start your protest there. Make sure you slap the opioids out of every patient's hands who are suffering from chronic pain. Call them an addict for kicks, even when they have a perfectly normal life.

Kratom is such a terrible overall experience. I did it recreationally a few times and it’s always headaches and nausea the next day in some kind of hangover that lasts multiple days.

I haven't heard of kratom being used by non-addicts, so I'm not surprised you wouldn't like it - it's like a non-smoker using nicotine patches. It's mainly used by people detoxing from stronger opioids.

I did it when I was coming off heroin (locked myself in my parents' country house for a fortnight or so, took ibogaine and kratom for withdrawals, came out fatigued but basically well). Even then, I found it extremely acrid and unappetising, and not even the resulting 'high' was particularly pleasant. I wouldn't ever take it if I weren't experiencing brutal heroin withdrawals.

You took ibogaine, a drug known to be cardiotoxic. You are a former heroin addict that is projecting your inability to use medicine responsibly onto other folks with medical conditions.

You talk about a high despite me never mentioning getting high, only the pain relieving effects. I could care less about a high. I use Kratom medicinally to help me live a better life.

I am sorry you took pain relieving agents and misused them. I'm sorry you thought street drugs like heroin were suitable quality and safe. I'm sorry for the pain you endured when withdrawing from these drugs. Now, I'm sorry you are projecting all of this on responsible users of much safer therapeutic agents.

There are lots of strains as well. You may have had a racier green strain. Red Mae Daeng would be closer to a conventional opioid.

Don't listen to /u/samhw. He clearly has no understanding of what it is to use something therapeutically versus in a maladaptive way. I on the other hand have a pre-med degree.

With any drug comes a bit of risk of addiction or dependency. Even antidepressants. Having a healthy attitude and lifestyle and avoiding the stronger things like oxycodone, heroin, methamphetamine, etc is wise.

/u/samhw please avoid discussing topics you know nothing about while labeling those who do as 'addicts.'

>The researchers looked at venom from 50 species before they found the black mamba's pain-killing proteins - called mambalgins

9y have passed, no new developments about this?

For as many times as the article stated they are "surprised" and "completely baffled", maybe they still are.

probably because mamba venom is crazy expensive.

Indeed. A quick search reveals nothing more than the original paper from 2012, cited just one time:

https://www.nature.com/articles/nature.2012.11526

I wouldn't be surprised if the venom was addictive too. I mean it isn't like it had any selective pressure for preventing or causing addiction. Although the latter may come as a side effect.

I can see a purpose for a multifaceted venom - both synergy of "speedballing" the lethal dose and making it harder biochemically for a creature to develop an immunity.

Like always with evolved systems purpose is an emergent thing by what reproduces and survives the best. It is a tautology of "things that spread and stay you have more of".

Surprised they didn't say whether it causes constipation. That's one of the most annoying side effects of morphine for most people.

(Maybe the original Nature article addresses this but it's paywalled.)

I passed a kidney stone a month and a half ago, and switched from a codeine-based painkiller to ibuprofen because of the constipation. (Also, for me, at least at the prescribed dose, codeine-with-acetaminophen/paracetamol gave less pain relief than 400 mg of ibuprofen. I'm also aware that morphine is significantly stronger than codeine.) The increased abdominal pressure from the constipation probably helped the stone pass a bit faster, but it also certainly seemed to increase the pain.

On a side note, drink plenty of water. 42 is pretty young for passing a kidney stone. Working from home this past year, my wife would give me a hard time that some days I drank only 500 mL or so of water. (I drank plenty of coffee in the office, but cutting down on coffee while working from home unfortunately didn't translate into replacing coffee with water.) My urologist says I should be drinking at least 30 mL of water per kg body mass per day. Yes, most of our food is mostly water, but at least for me, that didn't cut it. I've heard people compare passing a kidney stone to childbirth, but I'm sure that's a gross exaggeration. A really bad hangover is worse, but a kidney stone is painful enough that I was pretty useless for 5 days and could only sleep in a really hot bath, and then only for about 1-2 hours per day. You don't want a kidney stone.

I really hope this goes somewhere. I've been left on the curbside with a caduceus up my backside because of self-righteousness, paranoia and hysterics. If an analgesic can be created without committing the atrocity of inadvertently imparting a synthetic sense of wellbeing too, much suffering would end. Just don't poison it with acetaminophen! Maybe I'll abandon my unfruitful hunt for opium lettuce and raise snakes instead.

I understand exactly what you're saying and it's a shame you're currently being downvoted. People up in arms against opioids and in favor of all the restrictions that keep people suffering have clearly never experienced chronic pain. I don't want to downplay addiction risk, but everyone I have ever seen get addicted had it happen with severe mitigating circumstances like job loss, general financial insecurity, family history of addiction, things that made them susceptible. It was never just the pain and the painkillers. I took oxycodone for three years and never got addicted. It helped get me through the absolute worst years of my life until enough surgeries and physical therapy finally got me basically functional again. I guess I'm just lucky my doctors and insurers never gave into the pressure not to prescribe them, but I don't even know now what it would be like given the present state of legislation. My wife suffers from this tremendously on the other side, adult ADHD treated successfully and easily with Adderall, but it can't be filled out of state, can't be filled in advance. Makes it awfully difficult to work a job that requires 25% travel.

I wrote a lengthy, now deleted reply. I'm glad you recovered unscathed and I appreciate the balanced insight and story.

To those who through inhibition of self expression see all subjects as an arrow facing north or south, I pose a question for you to silently grate your arrows edge upon:

Is it for the greater good that pain be palliated with the chronic use of ibuprofen and perforated ulcers, or acetaminophen and failing livers, or any nsaid and heart disease?

Is insomnia now in fashion?

Is lethargy and unproductivity encouraged?

Or is it all a simple lack of empathy, characteristic of pampered narcissists who've acclimated to comfort since birth?

Or maybe an illustrious form of asceticism, an exhibition of impervious strength and endurance?

Fwiw - I enjoyed your posts The way I enjoy poetry : lovely, but largely incomprehensible.

I don't know if you're getting down voted due to people disagreeing or merely not understanding what your point and data is. It is possible if you contributed more clearly you'd find a more receptive audience.

I find frequently when there is topic near to people's heart aNd they spend a lot of time thinking about, they start at a hundred with a very strong and flowery language. My suggestion would be to understand others don't have same context and start at 1 and build your way up, whether logically or emotionally. You Gotta ask yourself are you writing for your own sake and enjoy your metaphors and alusions and poetry without regard for others (even finding gratification and martyrdom in not being understood), or are you actually trying to educate, persuade, build understanding. If the latter, focus on that goal most clearly and directly.

(I could be wrong - merely my 2 cents).

> merely my 2 cents

Two 1943 wheat pennies, I'd say. Thanks.

Snake bites can be abused too! https://news.ycombinator.com/item?id=20255373

No mention of Kambo (secretion from a tree frog) but it does contain opiate analogues as well

and so is a bullet, instant pain relief /s

Can’t feel pain if you’re dead.

shii...strap a tube to my arm and hit me with that mamba juice. be flying for hours...

or more likely arrested for animal abuse, but hey, imagine being the cool druggie who can get high and defend his territory with a snake. this under-bridge be mine.

Must be why this man does this: https://www.youtube.com/watch?v=ucpGlWnq8EE

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