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(BBC)   Scientists discover black mamba venom is 'better painkiller' than morphine. EVERYBODY MAMBA   (bbc.co.uk) divider line 32
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9364 clicks; posted to Main » on 04 Oct 2012 at 12:34 AM (2 years ago)   |  Favorite    |   share:  Share on Twitter share via Email Share on Facebook   more»



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2012-10-04 10:33:20 AM  
2 votes:

Great Porn Dragon: Doctors are REALLY loathe to prescribe ANY narcotics now because it's a very good way to get flagged as a "pill mill" and get the office shut down by the state.


As someone who has struggled with chronic pain for years, I can tell you it's not just doctors in KY who refuse to prescribe adequate pain meds & leave people to self-medicate. IMHO, western medicine in general does its best work when dealing with acute cases/emergency surgery, but fails miserably when dealing with chronic illness; it concentrates too much on chasing down symptoms & does not address root causes. Still, I always get excited when reading studies like the one in TFA; anything that sheds more light on how pain works & how we can control it is a good thing in my book.

Also, I'm enjoying reading your posts; sounds like you know your stuff (and I had no idea about the lizard spit thing...)
2012-10-04 04:48:57 AM  
2 votes:

werekoala: I've been feeling for years that it would be goddamn nice to have meds that actually block pain, instead of just overwhelming it with good feelings instead. Because while opiates make you not care about the pain, they can also make you not care about your family, job, house, etc.

And patients get accommodated so damn fast... All in all, opiates are a farking barbaric and frustrating stone age tool for us to be stuck with in the 21st century.

This stuff vs opiates sounds like the difference between dry cleaning your suit and trying to mask your funk with Axe.


That's one of the real niftinesses with ASIC-blockers, really--it's probably the first drug class we've found that actually blocks pain reception itself rather than overpowering things with Honey Badger levels of Not Giving A Crap by triggering opoid receptors (opiates) or acting as a COX inhibitor blocking prostaglandin production (NSAIDS and paracetamol/acetaminophen). The closest we've had to anything that worked on actual pain receptors was (of all things) capsaicin-based creams for arthritis, and that's just because those overwhelmed pain receptors--capsaicin is one of the few things that works directly on pain pathways as it is a calcium channel agonist and depletes substance P from neural pathways (Substance P being one of those neurotransmitters being associated with pain).

And it's my hope that this class makes it through clinical trials OK and we get more of a "surgical knife" rather than a blunt weapon to treat pain--much like ACE inhibitors revolutionised hypertension therapy, and much like GLP1 agonists are revolutionising type II diabetes treatment (the old oral anti-hypoglycemics were like trying to treat an accidental deep finger-cut with a tourniquet instead of pressure and stitches) for pretty much the exact reasons you specified--a good, effective, non-narcotic analgesic strong enough for surgical use that won't dope you up :D
2012-10-04 04:33:09 AM  
2 votes:

JustinCase: Great Porn Dragon: JustinCase: morg: It would be nice if they found a good pain killer that didn't get you high as well so they could sell it over the counter.

Suboxone and methadone don't?

No snark here. That's my impression and I'm not sure.

Actually, methadone could actually kill in a sufficiently high dose (basically enough to cause respiratory depression)--Suboxone would have less of a risk, due to the naloxone content.

Pretty much the reason for research into mambaglins is that there are certain categories of patients that--for various reasons--are "hitting the top" of what they can be safely dosed on opoids and are still in pain--usually spinal injury patients and cancer patients who are on their max doses of opiates and higher doses merely risk respiratory depression. We don't have a lot of good options for those populations, sadly, and even the opoid options we DO have are becoming less of an option in certain parts of the country due to problems with diversion.

(Here in KY, for instance, it's pretty much a major PITA getting anything scheduled for pain for more than a short period--thanks to a lot of folks dry counties out east realising they could crush up oxycodone tablets and sell them as "hillbilly heroin" as a cheaper high than even weed or beer. Suffice it to say that people who actually NEED pain relief have a hard time getting it, and even something injectable (a la insulin/Byetta pen) that couldn't be used to get you stoned would be an incredible boon here.)

Thank you for the detailed and insightful reply.

Does methadone provide a high of sorts?

Suboxone does not at all, ever. Correct?


Methadone and Suboxone are generally used for treatment of opoid addiction primarily because a) they don't get you AS stoned as other drugs in that class and b) it's more difficult to overdose on them. (The main reason suboxone really doesn't get you hugely stoned is because there's naloxone in it, which (of note) blocks some of the pain-relieving and "get you stoned" effects of the opoid in it; it's a similar approach to how they would put acetominophen/paracetamol in Vicodin to discourage you from OD'ing on it (we're REALLY starting to rethink that last one thanks to a lot of cases of quite accidental Liver Farkage from folks who took Vicodin and then took Dayquil or Extra Strength Tylenol with it--and yes, this happens more often than you might think). Naloxone is safer in this regards because the opoid-antagonist property of naloxone pretty much keeps you from getting all THAT high.) That said--it's still possible to get stoned off both, it just requires more effort.

The actual narcotic component of Suboxone (buprenorphine) can give a mild buzz (on the general level of hydrocodone/Vicodin but in very high doses does in and of itself have naloxone-like effects) and is used in pain control (without the naloxone) for these indications--which is also why it's still at a Schedule III most places, regulated just like Vicodin is. (And even the naloxone (and the fact that bupenorphine in high doses ACTS rather naloxone-like) doesn't really keep people from taking it recreationally--apparently it's becoming a new recreational opiate of choice in prisons due to drug diversion. Apparently it's abused much like oxycodone is, in fact.)

Of course, here in KY they're even kind of reluctant to give the stuff with naloxone out because of the fact that at least some enterprising folks have figured out how to essentially "wash" naloxone and paracetamol out of those drugs containing them AND due to the above drug-diversion problems--though the folks taking opiates for a buzz still prefer oxycontin because there it's a matter of "crush the tablet to get rid of the time-release". Doctors are REALLY loathe to prescribe ANY narcotics now because it's a very good way to get flagged as a "pill mill" and get the office shut down by the state.

(Seriously, I think the fact that Appalachia is (largely) dry has contributed to a LOT of drug crime that probably wouldn't be as severe if they could just hit a liquor store to get a bottle of cheap bourbon--if they can't get a buzz legally, they'll resort to the pharmacist's counter to do so or their friend who goes to the pill-mill doc in Florida.)
2012-10-04 03:48:11 AM  
2 votes:

Deman: AverageAmericanGuy: Great Porn Dragon: Chinese traditional medicine HAS used cobra venom (in non-lethal doses, of course) for pain relief

Homeopathy doesn't work for shiate


One of these statements is incorrect. Since the first seems to be a statement of fact and the latter a statement of opinion, let's just say that your opinion doesn't match the facts.

Homeopathy is one of those things that only .0001% of treatments work that can't be considered placebo. Ginger for an upset stomach(dilute it first, make a light tea with it or something) or a shot of osha/everclear tincture for congested lungs.

Research into venoms is pretty interesting. Due to the nature of how many of them work, there could be all sorts of positive effects we might find in them. The snakes just like to make you OD.


Pretty much. :D

And the reason I generally note that "Homeopathy doesn't do shiate"--most homeopathic preparations (at least that would be considered Strong Medicine by homeopaths) are diluted to such an exceedingly small degree that there is no real likelihood the active substance still remains in the homeopathic preparation at any detectable level. (To give an example--it's not uncommon to see 8X-12X preparations in stores, and even 24X in homeopathic sections of health-food stores; it's right at around the 12X mark that you start running into issues with stuff being actually detectable, and 24X dilution is where you start running into only having a 60% shot that a single molecule of the original substance still exists. Probably the most extreme concentration (and which, per homeopathic concepts, would be seen as Ultra-Powerful) is the preparation Oscillococcinium, which is a 400X dilution of a macerated duck liver and is at so weak a concentration at that level that you could dose two billion doses per second to six billion people for roughly the entire period the universe has existed after the Big Bang and STILL not get a single molecule originating from said duck liver.

Basically, anything with a number much above 6X/3C and you're seriously just wasting your money at that point, because you're basically just buying tap water.

(Note that I'm not discussing actual dilutions where the fluid extract of the plant or chemical in question is actually detectable, but then again by homeopathy this is (perversely) said to be too damn weak to be effective; actual fluidextracts of herbal preparations (not diluted to the point of absurdity) can be effective, but then again it's strong enough at that point that it's not considered a homeopathic remedy but actual herbal medicine at that point. :D Fluidextracts and essential oils and even herbal teas are quite a bit more concentrated than even the lowest-concentrated homeopathic remedy--and are also quite a bit more likely to actually be effective for their intended use (assuming such plant does in fact have medicinal properties) than an extreme dilution.)

(And I don't have a problem at all with herbal non-homeopathic remedies, provided that the stuff actually works, that is. Slippery elm bark tea DOES actually help with sore throats, and ginseng and ephedra tea do work as bronchodilators--at normal tea strength, not at a dilution so weak that not even the best lab equipment will EVER find a molecule of ephedrine, though. :D I'll generally use the proven-to-work stuff as a home cure or treatment...but IMHO, there's no use in buying weak-arse pills of Sambucol at a 12x concentrate (where there pretty much won't be the antioxidants you get elderberry extract for!) when you can go down to the liquor store and buy a bottle of Manishewitz elderberry wine (which is cheaper, and has a lot more of those antioxidants, and even if the antioxidants don't keep you from catching a cold...the alcohol will make you feel less miserable :D)...that's my point.)

I do think that people tend to confuse homeopathy (where stuff is diluted to the point of the ludicrous--then again, it was invented in an era where doctors were still regularly giving people mercury as a curative and Avogardo's Law wasn't yet understood) with dilution of toxins to the point of not being deathly toxic (the general principle behind making antivenom, also the basis of allergy shots); they also tend to confuse it with regular (not diluted to point of ludicrosity) herbal medicine (some of which has actually made its way to allopathic medicine) or molecular research into specific proteins (which is pretty much what happened here with the fortuitous discovery of mambaglins).

(Also, as a note--Chinese traditional medicine doesn't exactly practice homeopathy. The use of cobra venom in Chinese medicine involved making a fluidextract (basically making a form of snake wine with cobra venom) and then taking this orally--as cobrotoxin is less active via the oral route, people didn't poison themselves fatally.) Were homeopathic concentrations used (a la Oscillococcinium), they'd just be milking one snake a year and turning one snake's bile into medicine, not turning literally tons of snakes into various remedies and "snake wines" to the point some of these species are frankly endangered.)
2012-10-04 02:27:25 AM  
2 votes:
Also, mambalgins actually seem to trigger an entirely different pathway than opiates--this means there's actually a pretty good shot that they AREN'T addictive (NSAIDS aren't addictive in the sense opiates are, so it's not like there isn't precedent) and (in what may actually be a first in painkillers) actually seems to act on a major pain pathway (the "acid-sensing ion channel", probably the main pain pathway in humans).

Of course, it's going to require a fair amount of testing, and it's probably going to be about ten years before we see approvals of mambaglin analgesics (and that's if the drugs make it through the Phase I safety trials, the Phase II "ok, hopefully this doesn't have side effects that make people bletcherously ill", and the Phase III effectiveness trials where they compare it in humans with opoid analgesics)...but if the human trials turn out OK, this actually could give a REAL new option...especially in areas where docs are really reluctant to dispense opoid pain meds due to diversion risk (like in, oh, Appalachia) or in cancer or spinal injury patients where the pain is so severe that opoids don't work anymore without a risk of fatal respiratory depression.

This isn't gonna be an OTC thing, and is probably going to remain an injectable, but it might provide a pretty damn good alternative to people having to take morphine and fentanyl for pain...especially if (as it appears) it doesn't trigger the opiate receptors that actually get you high.

For those curious, the rather better summary on testing of mambaglin-1 and mambaglin-2 in mice is on Nature's website and Discover.com has a fairly decent layman's writeup--interestingly, this class of drugs may well not have any of the negative side effects of opiates, and if so, this could revolutionise pain management in the same way "lizard spit" GLP1 agonists have revolutionised treatment of type II diabetes.

(Plus, if we're lucky, maybe it'll get a smartass nickname too. I hereby vote that mambaglin-based analgesics be hereby dubbed "snakebite". :D)
2012-10-05 03:24:50 AM  
1 votes:
elephantswithoutborders.org

just keeping it real.
2012-10-05 02:56:48 AM  
1 votes:
Only because this song has been stuck in my head since I saw this post earlier...

Mambo Italiano

/Also, the gent dancing with Ms. Loren could be a pilot in that uniform of his.
//Never saw the movie, so not sure. 
///In case the link really won't work: http://youtu.be/i__PYqDbbx8
2012-10-04 09:07:29 PM  
1 votes:
Gawdzila:It's true, it isn't totally incoherent. The problem is that it makes sense only on that surface level. When you try to examine it deeply using the ideas that underlie our understanding of how the world works (atoms / physical chemistry / etc) it starts to make no sense at all.

In fact one of their most important and foundational principles of medicine -- the idea that water has a "memory" -- is deeply contradictory to some very basic principles of physics that form the foundation of thermodynamics and statistical mechanics. If you cannot treat one atom or molecule the same as another, it absolutely breaks the mathematics behind a lot of physics that has been understood and proven repeatedly since the industrial revolution.

Right. Hence ignoring the crazy parts. That's important. My initial comment was just that his didn't fit the surface level internal logic.
2012-10-04 09:03:10 PM  
1 votes:

I May Be Crazy But...: Gawdzila: I May Be Crazy But...: You know what he described isn't even homeopathy, right?

It certainly seems to resemble it. Homeopathic "medicine" is made of solutions that have been diluted to an absurd degree, sometimes things that can cause symptoms themselves.

But if you ignore the batshiat crazy parts, there is a certain internal logic to it.


It's true, it isn't totally incoherent. The problem is that it makes sense only on that surface level. When you try to examine it deeply using the ideas that underlie our understanding of how the world works (atoms / physical chemistry / etc) it starts to make no sense at all.

In fact one of their most important and foundational principles of medicine -- the idea that water has a "memory" -- is deeply contradictory to some very basic principles of physics that form the foundation of thermodynamics and statistical mechanics. If you cannot treat one atom or molecule the same as another, it absolutely breaks the mathematics behind a lot of physics that has been understood and proven repeatedly since the industrial revolution.
2012-10-04 05:20:35 PM  
1 votes:

Great Porn Dragon: WTFDYW: Great Porn Dragon
Thanks for the info on the gila monster venom. I have never heard of that. I must tell my in-laws to ask their doctor about this.

BTW: What do you do for a living that you know so much about this stuff?

The sad thing is that right now I'm actually technically unemployed (unofficially I do research but don't get paid for it)...job market has been shiat till recently and as I'll be having some outpatient surgery late this month it's hard to find an employer who will let you off for a few days afterward in your probationary period. Hopefully I'll be able to find something after the surgery, but the fact I've been in Consultancy Hell for the past ten years doesn't give me a whole lot of hope...but I would like to get something to put a bit more money in the bank for Deductible Hole Time, at least.

Most of what I've learned is basically from personal research, reading medical journals (and paleontological journals, and other scientific journal crap) for fun since I was a friggin' kid, and (in the very specific case of the Lizard Spit) having goddamn near my entire maternal half of the family going diabetic by the age of 45--the only relative I've had so far that's escaped was an uncle who died of a rare cancer before he got Teh Beetus. (It's a genetic thing, to the point the family been asked to be in studies; some of it may also have autoimmune aspects because that same familial side has a few type I's AND one or two other relatives who've had autoimmune issues (Guillain-Barre and an unspecified autoimmune neurological condition that was treated with a course of an early immunosuppressant called Imuran--and they've never had issues since other than type I diabetes and are Williard Scott Shout-Out levels of Well Matured :D). My dad's side at least doesn't have Teh Beetus but DOES have probable Lynch Syndrome, which means I get colonoscopies on top of all this--I should have a shiatload of genetic testing done but I'd rather put this off un ...


Well, get well soon so you can get backe to work. Thanks again for learnin me some new stuff. It was very, very interesting reading.
2012-10-04 02:31:59 PM  
1 votes:

Gawdzila: AverageAmericanGuy: It follows from homeopathic principles that something that would cause pain and death in sufficient quantities can be diluted and used as a pain reliever.

*facepalm*

Homeopathy is full of crap. They don't just dilute the venom, the isolate a particular peptide or peptides in it and use those at full strength.


You know what he described isn't even homeopathy, right? He's just making a joke.

I hope.
2012-10-04 08:56:24 AM  
1 votes:
As a guy who takes enough morphine every day to kill the average farker (200+ mg daily), all I can say is I hope the fda gets off their assess with this one.

/ hell, I can't even get sativex yet, and that's been in trials for years now

//next up- intrathecal pump or fentanyl patches...
2012-10-04 08:49:48 AM  
1 votes:
Great Porn Dragon
Thanks for the info on the gila monster venom. I have never heard of that. I must tell my in-laws to ask their doctor about this.

BTW: What do you do for a living that you know so much about this stuff?
2012-10-04 04:14:52 AM  
1 votes:
I've been feeling for years that it would be goddamn nice to have meds that actually block pain, instead of just overwhelming it with good feelings instead. Because while opiates make you not care about the pain, they can also make you not care about your family, job, house, etc.

And patients get accommodated so damn fast... All in all, opiates are a farking barbaric and frustrating stone age tool for us to be stuck with in the 21st century.

This stuff vs opiates sounds like the difference between dry cleaning your suit and trying to mask your funk with Axe.
2012-10-04 04:00:52 AM  
1 votes:
I can't believe people fell for AverageAmericanGuy's obvious homeopathy troll. Normally he's quite subtle at his trolling but that one was blatant.

Could the reason that mamba venom does this be some sort of evolved method to avoid their prey going in to massive convulsions prior to death which would increase the amount of toxins (lactic acid? I have no idea really) in them when they're eaten?
2012-10-04 03:00:22 AM  
1 votes:

AverageAmericanGuy: Great Porn Dragon: Chinese traditional medicine HAS used cobra venom (in non-lethal doses, of course) for pain relief

Homeopathy doesn't work for shiate


One of these statements is incorrect. Since the first seems to be a statement of fact and the latter a statement of opinion, let's just say that your opinion doesn't match the facts.


Homeopathy is one of those things that only .0001% of treatments work that can't be considered placebo. Ginger for an upset stomach(dilute it first, make a light tea with it or something) or a shot of osha/everclear tincture for congested lungs.

Research into venoms is pretty interesting. Due to the nature of how many of them work, there could be all sorts of positive effects we might find in them. The snakes just like to make you OD.
2012-10-04 02:46:12 AM  
1 votes:
Also, as a note on finding neat stuff in venom--part of why they started looking at black mamba venom is because there are ASIC agonists in other venoms (including other elapids like coral snakes) that have the opposite reaction of mambaglins--basically instead of knocking out the ASIC pain receptor they amplified the effects (which is why coral snake bites will have you screaming in pain in disproportionate level to the actual bite--also why stonefish stings are so godawful painful).

One thing that led to looking at Asian and African elapid and colubrid snake venoms is the fact that Chinese traditional medicine HAS used cobra venom (in non-lethal doses, of course) for pain relief, but cobrotoxin (the major neurotoxin in cobra venom) has the side effect that it's paralytic--mambaglins have the good analgesic effect, but without paralytic effects. :D (Homeopathy doesn't work for shiate, but sometimes non-homeopathic traditional medicine does give clues to researchers on productive areas to study.)

And expect a lot more interesting stuff to come out of venom research--we already have ACE inhibitors (an entire class of anti-hypertension drugs that came about via a discovery that bites from the jararaca--a Brazilian species of lancehead--dropped people's blood pressure like a rock), ziconotide (another powerful atypical analgesic coming from research in cone-snail venom--alas, as you basically have to have it injected by an intrathecal pump it's not seen a lot of utility outside of hospice care), the GLP1 agonists (from chemicals in gila monster venom) and now mambaglins...and there are a lot of other venoms being actively researched for Nifty Medical Applications to the point you could say it's a New Research Hotness. :D

(No, I'm not going to recommend you give a gila monster or a venomous snake a great big hug. You might thank them, though. ACE inhibitors in particular have really revolutionised hypertension management, and it's possible a rattlesnake's cousin could have saved many lives.)
2012-10-04 02:16:22 AM  
1 votes:
media.tumblr.com
2012-10-04 02:12:18 AM  
1 votes:
No weirder than the New Hotness in type II diabetes medications being--I am not making this up--three generations of a GLP1 agonist that was originally discovered in gila monster venom, to the point that pretty much this entire class of drugs has the affectionate nickname of "lizard spit". Bonus--it also seems to give the same general benefits (reduction in appetite, improvement in glycemic control particularly with glucagon regulation, and weight loss) as weight-reduction surgery only without the 25% death risk. :D

And no, they did NOT to my knowledge have gila monsters happily nomming folks with Teh Diabeetus (as odd a mental image as that may be)--the scientists in question already knew about human GLP1 agonists as a target (the human version having a very short in vivo half-life, though) and found a similar compound that is much longer-lasting in gila monster venom.

(Yes, a lot of venoms do tend to be targets for pharmaceutical research--there's at least one painkiller in the pipeline (if not already approved) based on a cone-snail neurotoxin. Mambas have a particularly potent neurotoxin (not quite on the level of, say, Australian elapids but close and quite a bit easier to milk) so it's not a huge shocker that some painkiller based on mamba neurotoxins is in the pipeline.)

/yeah, have a relative or three on the lizard spit
//the stuff does work better than oral hypoglycemics, and Lizard Spit 3.0 only has to be injected once a week--even the older versions of Lizard Spit aren't as bad as insulin or the oral hypoglycemics
2012-10-04 01:57:24 AM  
1 votes:
How long before black mamba venom is a controlled substance?
2012-10-04 01:48:19 AM  
1 votes:
De'Anthony Thomas can't be caught.

/go ducks
2012-10-04 01:28:29 AM  
1 votes:
DNRTFA

Death kills the pain forever.
2012-10-04 01:22:54 AM  
1 votes:
Which Mamba variety though? - there are several after all. Is it Mamba #1, Is it Mamba #2, Is it Mamba #3, Is it Mamba #4 or is it ... Mambo #5 ?



A little bit of Monica in my life, a little bit of Erica by my side / A little bit of Rita is all I need, a little bit of Tina is what I see / A little bit of Sandra in the sun, a little bit ...
2012-10-04 01:03:16 AM  
1 votes:

AverageAmericanGuy: It follows from homeopathic principles that something that would cause pain and death in sufficient quantities can be diluted and used as a pain reliever.


*facepalm*

Homeopathy is full of crap. They don't just dilute the venom, the isolate a particular peptide or peptides in it and use those at full strength.
2012-10-04 12:54:53 AM  
1 votes:
img688.imageshack.us

A new drug? One that won't make me sick?
2012-10-04 12:51:04 AM  
1 votes:
Heroin is a better painkiller too.... so what?
2012-10-04 12:48:47 AM  
1 votes:
Ride the snake

www.aaroncampbell.org
2012-10-04 12:48:25 AM  
1 votes:
It follows from homeopathic principles that something that would cause pain and death in sufficient quantities can be diluted and used as a pain reliever.
2012-10-04 12:48:01 AM  
1 votes:
www.corporate-aliens.com

"Pay attention, this part pertains to you..."
2012-10-03 09:25:46 PM  
1 votes:
"La,la,la,la,la,la bmamba..."
2012-10-03 06:50:06 PM  
1 votes:
Who cares about the side affects.

It's the after affects that f you up.
2012-10-03 05:53:51 PM  
1 votes:
I laughed at this. No clue why exactly but +1 for it anyway
 
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