Morphine Apparently in Your Head

[Soda]

Morphine Apparently in Your Head

Several persistent researchers finally have proof for a theory they have held for more than a decade, despite dissent from the larger scientific community: Morphine occurs naturally in the human brain.
Most scientists have been skeptical of the claim, saying previously studied samples were likely contaminated with morphine molecules. But a paper published in the Sept. 21 issue of the Proceedings of the National Academy of Sciences (http://www.pnas.org/cgi/content/abstract/0405430101v1?view=abstract) seems to put the question to rest.
Meinhart Zenk and his colleagues at Martin-Luther-University Halle-Wittenberg (http://www.uni-halle.de/MLU/index_e.htm) in Germany found that human cells grown in a dish synthesized morphine.
"Without doubt, human cells can produce the alkaloid morphine," Zenk wrote in the paper. "The studies presented here serve as a platform for the exploration of the function of 'endogenous morphine' in the neurosciences and immunosciences."
In other studies, researchers had found trace amounts of morphine in human and other animal tissues, but only a handful of believers thought morphine occurred naturally in the brain. Most assumed it came from foods like hay, lettuce, milk and rabbit feed that contain the chemical.
If Zenk's paper finally convinces scientists that morphine is as natural a presence in the brain as serotonin or dopamine, it will open new doors for looking at the treatment of pain, addiction and other health issues, said George Stefano, director of the Neuroscience Research Institute at the State University of New York at Old Westbury (http://www.oldwestbury.edu/).
Stefano also has a paper (http://www.nel.edu/Press/Latest_from-the-office.htm2505) coming out in the Oct. 5 Neuroendocrinology Letters showing that animal neural tissue can synthesize morphine.
Instead of pumping patients full of morphine, Stefano said, doctors could instead give a morphine precursor -- a molecule that would set off a chain reaction eventually resulting in increased morphine production in the brain. Stefano, who has championed the existence of morphine in the brain for years, published proof of such a precursor, called reticuline, in the journal Molecular Brain Research in 2003.
The approach could circumvent dependency because it would increase an individual's own morphine levels instead of replacing natural morphine with a synthetic version. Similarly, a drug called levodopa, a precursor to dopamine, is commonly used to treat Parkinson's disease.
The discovery could also explain why some people are more susceptible to addiction -- they may have a morphine deficiency.
"All of a sudden," Stefano said, "(morphine-deficient individuals) take this compound (and) it really makes them feel not only good but normal."
A morphine deficiency could also be the cause of some chronic pain, Stefano said.
The researchers believe morphine is created by neurons in the brain, but much about the production remains mysterious. They found morphine in the limbic center, which is involved with emotions.
"That puts this new signaling molecule in a very crucial part of the brain," Stefano said. "If morphine's there, it's involved with subjective thinking."
Stefano hopes that the realization that morphine is endogenous (meaning it's produced within an organism) will lessen morphine's association with abuse, and increase the amount of research on naturally occurring morphine. With only about 15 scientists concentrating on endogenous morphine, progress is slow going.
"In science, painstaking trial and error are big part of your life," he said. "But it's much harder when most people don't believe you.":(


Below is another piece of information that seemed relevant, or at least useful in conjunction with the above information which strikes me as nothing less than a breakthrough. The below images appear to be a PET scan, a process which uses radioactive particles to show how a brain is functioning, as opposed to something like a non-radioactive MRI which simply shows structure. Areas in red show "high metabolic activity", basically where blood in concentrated.
When we eat, blood goes to our stomachs. When we exercise, it goes to our muscles. The result of this action is increased digestion, and increased muscle gain. Therefor, one might imagine that increased blood flow to the brain while under opiates is actually beneficial to cognitive power.

http://www.opiates.org/images/brain_normal.gif(non-opiated)

"Opiate Dependency is a physical illness involving a central nervous system disorder caused by long-term opiate intake."
http://www.opiates.org/images/brain_opiates.gif(opiated)

"There are several types of opiate receptors, including the delta, mu, and kappa receptors. Each of these three receptors is involved in controlling different brain functions. For example, opiates and endorphins are able to block pain signals by binding to the mu receptor site. The powerful new technology of cloning has enabled scientists to copy the genes that make each of these receptors. This in turn is allowing researchers to conduct laboratory studies to better understand how opiates act in the brain and, more specifically, how opiates interact with each opiate receptor to produce their effects. This information may eventually lead to more effective treatments for pain and opiate addiction."
- http://www.opiates.org/opiates.htm (http://www.opiates.org/opiates.htm)

[EleusisII]

Say what!?!?


hay, lettuce, milk and rabbit feed that contain the chemical.

[EleusisII]

Besides my surprise at hay containing morphine, might I suggest to change the question from the vague "could" to a definite "does".
A lot of things "could" be. There could live a man on the moon, or I could win a millions dollars. But DO i have morphine deficiency? That is the question.

[Soda]

Besides my surprise at hay containing morphine, might I suggest to change the question from the vague "could" to a definite "does".
A lot of things "could" be. There could live a man on the moon, or I could win a millions dollars. But DO i have morphine deficiency? That is the question.

First of all, I never noticed that thing about the hay containing morphine. Alright, I noticed it, but I only feel like backing up your politely stated WTF now that I see it wasn't just me that found it odd.

Secondly, you couldn't be more right about the poll. But unfortunately, there is no way I know of to change it. If a mod could help me out, I'd appreciate it. Otherwise, the whole poll is pretty much the same as saying, "could I go to the grocery store tommorow?"

In the meantime, I'm going to have some milk with a side of hay.

[robojunkie]

Fixed. And, based on this study, apparently demonstrating fairly conclusive its presence in mammalian (incl. human) brains, it would seem reasonable like any other small molecule neurochemical deficiency, that a lower than average endogenous morphine level could exist in humans. This would be a good correlation with evidence that addictive behavior patterns have a very significant genetic/hereditary component, which implies some sort of chemical make up difference in those genetically predisposed. However it would also be relevant to know how important (and how much) endo-morphine is in the various neurological processes, especially in relation to endorphins/enkephalins. Another interesting question(s):

1) If we make endorphins/enkephalins and all the opioid receptors have endogenous polypeptide ligands, why do we need/have natural morphine (biologically speaking, of course we "need" it)?

2) How the hell would the receptor differentiate between morphine and morphine? If the same structure, well, its the same structure. There's no magical genetic "tag" on it to trick the receptor.

However, Q2 could be related to potential research into what processes tell the neuron to grow more receptors/induce endocytosis of receptors when in presence of morphine. Like is there a certain small level naturally present that the brain "expects" and so doesn't adapt? What if the endo-morphine was blocked? Would an opposite response, vis a vis tolerance and withdrawal, occur? Anti-tolerance? Remove the blocker and we "withdraw" by getting excessively opiated? Wow...

What I'm trying to say it that where the reticuline is mentioned and its potential to serve as a morphine bioprecursor, if tolerance to our own doesn't occur their must be some simultaneous (to endo-morphine release) process that inhibits the development of opioid tolerance. Find the transmitters/enzymes in this process, then you have a chance at discovering the keys to the development of tolerance and the potential to develop analogues to prevent it with exo-morphine and other opiates. I would love to know the answer to question 2, because if it is different somehow, this would breakthrough I've been waiting for, as far as pharm research goes.

Imagine, being able to trick the brain into thinking your opiates are really produced internally and naturally tolerated, without induction of the tolerance/addiction process!

[I-Nod]

Man, RoboJ... you got me all hyped up reading that! Heh. Just imagining the possibilities...

[eerased]

Everytime I "Try" to read one of these posts he does I feel like I hafta go sit in the corner for an hour for not paying attention in class...

Now I'm gonna try and read it again...:p


Fixed. And, based on this study, apparently demonstrating fairly conclusive its presence in mammalian (incl. human) brains, it would seem reasonable like any other small molecule neurochemical deficiency, that a lower than average endogenous morphine level could exist in humans. This would be a good correlation with evidence that addictive behavior patterns have a very significant genetic/hereditary component, which implies some sort of chemical make up difference in those genetically predisposed. However it would also be relevant to know how important (and how much) endo-morphine is in the various neurological processes, especially in relation to endorphins/enkephalins. Another interesting question(s):

1) If we make endorphins/enkephalins and all the opioid receptors have endogenous polypeptide ligands, why do we need/have natural morphine (biologically speaking, of course we "need" it)?

2) How the hell would the receptor differentiate between morphine and morphine? If the same structure, well, its the same structure. There's no magical genetic "tag" on it to trick the receptor.

However, Q2 could be related to potential research into what processes tell the neuron to grow more receptors/induce endocytosis of receptors when in presence of morphine. Like is there a certain small level naturally present that the brain "expects" and so doesn't adapt? What if the endo-morphine was blocked? Would an opposite response, vis a vis tolerance and withdrawal, occur? Anti-tolerance? Remove the blocker and we "withdraw" by getting excessively opiated? Wow...

What I'm trying to say it that where the reticuline is mentioned and its potential to serve as a morphine bioprecursor, if tolerance to our own doesn't occur their must be some simultaneous (to endo-morphine release) process that inhibits the development of opioid tolerance. Find the transmitters/enzymes in this process, then you have a chance at discovering the keys to the development of tolerance and the potential to develop analogues to prevent it with exo-morphine and other opiates. I would love to know the answer to question 2, because if it is different somehow, this would breakthrough I've been waiting for, as far as pharm research goes.

Imagine, being able to trick the brain into thinking your opiates are really produced internally and naturally tolerated, without induction of the tolerance/addiction process!

[youwonhundred]

Everytime I "Try" to read one of these posts he does I feel like I hafta go sit in the corner for an hour for not paying attention in class...

Now I'm gonna try and read it again...:p

I thought I was the only one.

[eerased]

Yippy I was beginning to think I was the only one.. I've reread it a couple times I'm starting to get the jist I think...LOL
I thought I was the only one.

[StrungOutAgain]

I read this while opiated and understood it so it really does help cognitive power. Anyway I really hope this study is able to go on. I could imagine there being some pharms who might not like this if it turns it out there is a true precursor to 'brain morphine'. Okay so there is one thing I'm not sure about here and that is:



2) How the hell would the receptor differentiate between morphine and morphine? If the same structure, well, its the same structure. There's no magical genetic "tag" on it to trick the receptor.


Call me stupid but I fail to understand what you meant by morphine and morphine? Do you mean morphine and brain morphine? I feel we should all call it brain morphine or maybe BM for short so it can differentiated. Anyway I'm far from a chemist but I think that the brain somehow knows which is which since it knows if its getting morphine from elsewhere such as pills, IV, etc. It can tell the brain to stop producing morphine and therefore dependence happens. Wait does the brain produce morphine right now as is? Sorry I'm just a bit confused on this, I seem to have more questions then answers at this point but I'm really intrigued by this and want to learn more. Also I'm very sorry if none of this makes sense to any of you or if it confuses you somehow. I could very well be wrong about what I think on this and if I am tell me cause I want to know how it really works.

One more question has come to mind, sorry I know this has been a long enough post as it is. So is the production limited to just the brain? Since it was said that human cells could produce morphine. Now granted I realize that it would only be of use once it hits the brain. Now I know this might not have an answer but do you think there is a limit to exactly how much the brain would be able to produce morphine at a time? Also how would this change overdoses or even if it would? I would think that the brain would know when to quit producing morphine if it was near an overdose. Okay I'm seriously done for now. one more apology sorry if any of my thoughts or questions seem stupid. :confused:

[Dr. Oxy]

2) How the hell would the receptor differentiate between morphine and morphine? If the same structure, well, its the same structure. There's no magical genetic "tag" on it to trick the receptor.



Robo there well may be small differences between the endogenous morphine and the synthetic one. Though primarily the same molecule, made of the same atoms, there may be some undiscovered surface receptors that could lead to a differentiation in the body.

[OxyContinuously]

I know the brain produces endorphin and enkaphalin which are chemically similar in structure to morphine, but morphine itself?

I'd vote NO, but a nice idea anyway!

[aj11]

Also ketaimie in your brain, that explains near death experineces

[SpecialGuy69]

I just always assumed that M was produced in the brain. Never thought there was a question about it. It is possible the endo-M is used for other purposes than making you feel high- it could also act on other parts of the body, especially those where M has known effects, such as digestive system, histamine response systems, sleep/wakefulness cycles, etc.

[Synack]

so we all just need to mass order this precursor before its regulated...

[jacky]

yeah, the brain produces morphine....

scientists have been researching this for the last ten years at least.

apparently the biosynthesis follows pretty much, the opium poppys same synth.

but I think that there is some complications when taking reticuline or salutaridine and expecting a full conversion of those compounds into thebaine and eventually morphine.

hell, scientists for at least a few years have labeled thebaine as a substance that might produce narcotic actions, and be a possible substance with abuse potential, due to its apparent conversion into morphine after a few hours in primate bodies. The UN scientists were the first I think to consider thebaine a possible narcotic, not considering that it might be used to convert to morphine or heroin, but that taking thebaine alone will produce eventually, narcotic effects.

if a person cant process codeine though, I would suspect that thebaine is only going to cause toxicity.

morphines presence in trace amounts in mammilian milk should have clued scientists of this possibility a long time ago...

I think the possibility that a compound that occurs naturally within an individual could be considered either deficient, sufficient, or MORE than sufficient is obvious....if the body produces the compound in any amount, well, most likely in my opinion you have the chance that those levels might fluctuate.

where else are we going to find morphine?
I wouldnt be suprised if it pops up somewhere in the magnolia family, and its possible that it might occur in other, unknown plant species as well, isoquinoline chemistry is pretty common in the plant world.

the good news is that plenty of plants produce salutaridine and reticuline.

[mark_renton]

First of all, I never noticed that thing about the hay containing morphine. Alright, I noticed it, but I only feel like backing up your politely stated WTF now that I see it wasn't just me that found it odd.

Secondly, you couldn't be more right about the poll. But unfortunately, there is no way I know of to change it. If a mod could help me out, I'd appreciate it. Otherwise, the whole poll is pretty much the same as saying, "could I go to the grocery store tommorow?"

In the meantime, I'm going to have some milk with a side of hay.


cuse me for a sec I got a whole barn full of hay, need to go find some stupid teenagers, I"M GONNA BE RICH BITCH!

[Soda]

where else are we going to find morphine?
I wouldnt be suprised if it pops up somewhere in the magnolia family, and its possible that it might occur in other, unknown plant species as well, isoquinoline chemistry is pretty common in the plant world.

You have a scientific mind jacky, havent seen this side of you before. Sort of makes you think, why poppies?
Why does this plant have such a hardon for producing morphine? Makes you also wonder what else the morphine family of narcotics are good for. We all know plants don't have a brain or a central nervous system, but they wouldn't produce these alkaloids for no reason.
We know so much about what is produced in our body that we ISOLATE it, just like we did with morphine and such.
As you know, "vitamins" and "antioxidants" (found in every pharmacy) are just products of our own very human bodies. Just like the opium poppy, we are machines that create chemicals. It's funny, I think.

Yet when we look at the opium poppy, and see all the drugs that have been made from it, we don't stop for a second to think about the poor little poppy itself. What are chemicals like morphine and thebaine actually FOR? Why are they made by such a weird little plant?
Sure, they produce pain relief in humans, but do plants have pain? Do they need relief? You know. It's a question that should be answered, but hasn't.
Not only that, but now that we know morphine is made in other plants it makes us wonder even more why morphine even exists. It also reminds us of one almost eerie fact...opiates WERE NEVER INVENTED. Almost makes you open your bible.

[EleusisII]

Why does the poppy make morphine? Speculation, but I suppose evolution might have something to do with it... The alkaloids in the plant could have made it a staple of some animals diet, thereby ensuring that the seeds get spread far and wide.
From what I understand, many plants have evolved that technique: Being yummy enough to eat, means that your seeds have a very good chance of surviving and being spread.

Something that has always interested me, is how our brain have cannabinoid receptors: receptors specifically designed for cannabis and related compounds. I know that there is a lot of research going on into said compounds, and why/how they exist inour brain. There's also research that show that they protect agains neuro-toxicity.

[SurfRat]

I hope there is something of use in there,

I was to think there might be nothing but open space...

WooHoo

300

[SpecialGuy69]

I think mushrooms make psylobibin/psylocin to deter animals from eating them... Smart move, mushroom! Now every hippie on earth picks you!

But seriously, usually when there are high concentrations of active chems in a plant, there is a very simple explanation like that.

Or, think why does a ripe orange taste so fuckin good?

[mikells43]

there actually is a chem 100x than morph in ur body if what i learned in my one rehab is right.

[EleusisII]

I wouldn't trust anything you hear in rehab very much Mikeells ;)

Next time you're there, could you ask if you have to plug it, or IV it?

[mikells43]

i forget what the real name for it is, i have to ask someone but i didnt understand addiction then and i really didn't put 2 and 2 together. but ill get a name for it sometime.

[Nostromos]

Maybe that's why I'm so depressed all the time, not enough morphine in my head.

[robojunkie]

Call me stupid but I fail to understand what you meant by morphine and morphine? Do you mean morphine and brain morphine? I feel we should all call it brain morphine or maybe BM for short so it can differentiated. Anyway I'm far from a chemist but I think that the brain somehow knows which is which since it knows if its getting morphine from elsewhere such as pills, IV, etc. It can tell the brain to stop producing morphine and therefore dependence happens. Wait does the brain produce morphine right now as is? Sorry I'm just a bit confused on this, I seem to have more questions then answers at this point but I'm really intrigued by this and want to learn more. Also I'm very sorry if none of this makes sense to any of you or if it confuses you somehow. I could very well be wrong about what I think on this and if I am tell me cause I want to know how it really works.

The quote about morphine and morphine was intentionally sarcastic. If we truly have endogenously formed morphine (and not "morphine like" whatever) there is a reasonable assumption we don't become tolerant to it, as this would be counterproductive to the purpose it would serve. That quote was an attempt at asking the rhetorical question: "How does the brain (or anything) tell poppy morphine from homo sapien morphine? Well, it either can't, and this means tolerance won't develop to a limited samll amount, or much better, it can, but since the molecules are identical (morphine is morphine) how can the mu receptor "tell" whether or not to adapt? Well here's the answer: It couldn't. OK, then one would ask, how come you don't get "addicted" to your own morphine, slowly making more and more? Well my theory would be, and has been for awhile, that there are intracellular processes that correspond to the release of natural endorphins and "endo-morphine" that essentially must let the downstream neuron know to "expect" morphine and not initiate the development of tolerance.

Think about it, you take exo-morphine and your brain does not produce or expect it (in fact physiologically speaking, it doesn't want it either), the brain's response is to re-establish homeostasis, which is just body equilibrium, by inducing tolerance to the "imbalance" caused by morphine. Therefore if we have naturally occurring morphine in our brains, and we don't become tolerant to it, it seems apparent to me that either A) there is a simultaneous release of another transmitter from the morphine releasing cell (or one near it) that is directed towards the cell with the MOR, and this transmitter is what would be "informing" the next cell that it should be getting the M. Therefore, that transmitter initiates some process (or inhibits some process) related to the adaptation of the receptor count to morphine concentration or B) similar to A, the release of morphine also stimulates release of another NT to another cell, which then communicates with the MOR containing cell, again inhibiting the tolerance development

Now, the really really important part for us junkies: If the M releasing cell is also involved in carrying an "artificial vs natural" message to the receiver cell, ie one that only occurs on release of morphine from a cell, this is prima facie evidence that there exists in us a biochemical pathway directly relating opiate source to the tolerance phenomena, and that this pathway initiates a process within the receiving neuron that completely inhibits the development or even initiation of the tolerance process.

Think about it, this could, in theory lead to a pill that we all could take at whatever required frequency on a regular basis (like an AD), but this then tricks the receiving (MOR) cell into thinking the copious amounts of morphine/oxymorphone/fentanyl/etorphine on its MORs are really just NTs released from the upstream cell.

Fucking amazing if true and possible. So, the initial question, answered, is this: the brain, neurons nor anything else can tell the "mann (bio)made" and the "man (farm/chem) made" apart, without some requisition sheet or receipt that comes with the biomorph (ie the sheet/receipt is that second NT). The injected (it better be or I'm pressing charges for violation of basic Opiolaw!) morphine, not coming from the first cell, would also not have a corresponding "no tolerance" signal. Therefore, if the brain can differentiate "morphine from morphine" than there is an extremely good chance that this pathway's receptor can be mapped, the enogenous NT/ligand discovered, SAR's accomplished that a range of molecules could be prepared with anti-Tollerancene activity. (Yes, the NT is called tollerancene, kidding).

Just fucking imagine this, that second pathway of neural communication can lead directly to the deveopment of a daily pill that could quite possibly block the development of tolerance in us junkies, and also quite possibly block the loss of tolerance on kicking. But after one last shitty kick, we wouldn't have to worry about that anymore, huh?!?!?!

[robojunkie]

Oh, yeah, mikells or barney or whoever was debating this, that powerful ~100 x morphine chem is called "Beta-endorphin". However it is neither more powerful than etorphine (~2,000-4,000 x morphine) nor carfentanyl (5,000-10,000 x morphine). Etorphine is, IMO, the Supreme Lord and Master of all "semi-synthetic" opiates, and is only 3 steps from theibane. Carfentanyl can be made the same way as fentanyl with the addition of 3 to 6 steps, depending on the methodology used. These two opioids are, to the best of my knowledge, the strongest opioids out there right now, at least with a good body of scientific research showing this to be the case definitively.

I have also read and heard a number anecdotal reports that etorphine is the most pleasurable of all opioids...
z

[Soda]

Call me stupid but I fail to understand what you meant by morphine and morphine? Do you mean morphine and brain morphine? I feel we should all call it brain morphine or maybe BM for short so it can differentiated. I think that the brain somehow knows which is which since it knows if its getting morphine from elsewhere such as pills, IV, etc. It can tell the brain to stop producing morphine and therefore dependence happens. Wait does the brain produce morphine right now as is? Sorry I'm just a bit confused on this, I seem to have more questions then answers at this point but I'm really intrigued by this and want to learn more. Also I'm very sorry if none of this makes sense to any of you or if it confuses you somehow. I could very well be wrong about what I think on this and if I am tell me cause I want to know how it really works.

One more question has come to mind, sorry I know this has been a long enough post as it is. So is the production limited to just the brain? Since it was said that human cells could produce morphine. Now granted I realize that it would only be of use once it hits the brain. Now I know this might not have an answer but do you think there is a limit to exactly how much the brain would be able to produce morphine at a time? Also how would this change overdoses or even if it would? I would think that the brain would know when to quit producing morphine if it was near an overdose.


I don't think that the brain stops producing natural opiates just because you start taking synthetics. I think what happens is that the brain is geared to survive, and let the body survive, as though we were still caveman. You can't run from a lion if you were under the influence of a plant chemical that debilitated you. So what the brain does is become tolerant, a good thing from the brain's point of view, so that the drug you must be getting in your diet doesn't debilitate you so much.
This may be totally a lie, but my art teacher claims there is arsenic in apple seeds, and that he ate so many apple seeds every day for so many years that when a doctor took his blood he found almost lethal doses of arsenic in him, but saw no physical ill effects. If it was true, it could be an example of tolerance.

There's a chemical in rhubarb that the body mistakes for calcium, and you end up getting poisoned if you eat too much. But if you eat a little over a while tolerance comes in and saves you.


Okay I'm seriously done for now. one more apology sorry if any of my thoughts or questions seem stupid. :confused:
Never, never, never call yourself stupid. If you hadn't spent so much energy making clear to us how stupid you are, you couldve used some of that energy to ask us a direct question.

[Soda]

Powerful ~100 x morphine chem is called "Beta-endorphin". However it is neither more powerful than etorphine (~2,000-4,000 x morphine) nor carfentanyl (5,000-10,000 x morphine). Etorphine is, IMO, the Supreme Lord and Master of all "semi-synthetic" opiates, and is only 3 steps from theibane. Carfentanyl can be made the same way as fentanyl with the addition of 3 to 6 steps, depending on the methodology used. These two opioids are, to the best of my knowledge, the strongest opioids out there right now, at least with a good body of scientific research showing this to be the case definitively.

Fentanyl is also 100 times the power of morphine. See:


The synthetic drug is too potent, at 100 times the strength of morphine, to be placed in the hands of the general public


Yet beta endorphin, an endorphin (surprise surprise) is allegedly the same potency but is different chemically. It also doesn't cause problems.

endorphins are endogenous (http://www.answers.com/topic/endogenous) opioid (http://www.answers.com/topic/opioid) biochemical compounds. They are polypeptides (http://www.answers.com/topic/peptide) produced by the pituitary gland (http://www.answers.com/topic/pituitary-gland) and the hypothalamus (http://www.answers.com/topic/hypothalamus) in vertebrates (http://www.answers.com/topic/vertebrate), and they resemble the opiates (http://www.answers.com/topic/opiate) in their abilities to produce analgesia (http://www.answers.com/topic/analgesic-1) and a sense of well-being. In other words, they might work as "natural pain killers." Using drugs (http://www.answers.com/topic/drug) may increase the effects of the endorphins.

So...back to you and your cryptic scientificy post...

100 x morphine chem is called "Beta-endorphin". However it is neither more powerful than etorphine (~2,000-4,000 x morphine) nor carfentanyl (5,000-10,000 x morphine).

Beta endorphin is very different from all the other drugs you've listed.
I don't understand how a drug like etorphine (which you say is 2,000x morphine) can be "no more powerful" than a drug like carfentanyl (which you say is 5,000x morphine)

Etorphine is, IMO, the Supreme Lord and Master of all "semi-synthetic" opiates, and is only 3 steps from theibane.Etorphine may be the Supreme Lord and Master of all semi-synthetic opiates, and similar to our natural friend theibane...but it's used to knock out wild animals. If by some stroke of fortune/mistfortune you find your elusive king, please be careful before you bow to him, or he may smack you off the barstool like the wild animal u r.

Lastly:

I have also read and heard a number anecdotal reports that etorphine is the most pleasurable of all opioids...
I and others would love to see them. I searched erowid and came up dry.

[robojunkie]

So...back to you and your cryptic scientificy post...
Beta endorphin is very different from all the other drugs you've listed.
I don't understand how a drug like etorphine (which you say is 2,000x morphine) can be "no more powerful" than a drug like carfentanyl (which you say is 5,000x morphine)
Etorphine may be the Supreme Lord and Master of all semi-synthetic opiates, and similar to our natural friend theibane...but it's used to knock out wild animals. If by some stroke of fortune/mistfortune you find your elusive king, please be careful before you bow to him, or he may smack you off the barstool like the wild animal u r.

Yeah dude I'm well aware of 1. Beta endorphin is a protein, containing within its over 100 AA residue structure the pentapeptide structure for enkephalins.

On number two, you apparently have misread my statement, which said the etorphine and carfentanyl are both more powerful than the endorphin. I never said what you have quoted in your inference. It would make no sense for me to list numbers indicating CarF being stronger than Et, then say the opposite. Why would I write that?

Thirdly, I have worked with numerous "Level 6" toxins, and one who is careful, well informed and knows what the hell they are doing would have no problem handling any of these. After all who the hell made them, God??? No, Janssen and Bentley, both humans in the same profession as I, right? How do you think they make "sheets" of acid? They heavily dilute before spotting. Get it.

I'd love to know the difference between not understanding a post and "cryptic scientificy" post. There's nothing cryptic about it. Are you having another hangover day/early start on the night? You seem a little pissed in that post.

Edit: Please don't patronize me with corrections/assertions on fent's relative potency to morphine, especially quoting a newspaper. Don't you think I'd already know this, which by the way, is technically about 80 to 1 fent/morphine. Last I saw, newspapers can't handle more than one "number invoved" article a day w/o fucking it up or generalizing.

[Soda]

Yeah dude I'm well aware of 1. Beta endorphin is a protein, containing within its over 100 AA residue structure the pentapeptide structure for enkephalins.

On number two, you apparently have misread my statement, which said the etorphine and carfentanyl are both more powerful than the endorphin. I never said what you have quoted in your inference. It would make no sense for me to list numbers indicating CarF being stronger than Et, then say the opposite. Why would I write that?

Thirdly, I have worked with numerous "Level 6" toxins, and one who is careful, well informed and knows what the hell they are doing would have no problem handling any of these. After all who the hell made them, God??? No, Janssen and Bentley, both humans in the same profession as I, right? How do you think they make "sheets" of acid? They heavily dilute before spotting. Get it.

I'd love to know the difference between not understanding a post and "cryptic scientificy" post. There's nothing cryptic about it. Are you having another hangover day/early start on the night? You seem a little pissed in that post.

Edit: Please don't patronize me with corrections/assertions on fent's relative potency to morphine, especially quoting a newspaper. Don't you think I'd already know this, which by the way, is technically about 80 to 1 fent/morphine. Last I saw, newspapers can't handle more than one "number invoved" article a day w/o fucking it up or generalizing.

I really didn't mean to patronize you.
This was supposed to be a scientific study, and the reactions of people who read it. I understand it was hard for some to understand, but chemistry has always been mind boggling, and I don't want to patronize the only person on the thread who really understands this stuff.

[SpecialGuy69]

I really didn't mean to patronize you.
This was supposed to be a scientific study, and the reactions of people who read it. I understand it was hard for some to understand, but chemistry has always been mind boggling, and I don't want to patronize the only person on the thread who really understands this stuff.So everyone else posting on this thread is just some idiot who really doesnt understand it? Except for you, of course.

[Soda]

You're way out of line. Get off my thread.
-Soda

[Soda]

Sorry, uhm, I just meant agent orange. Agent orange kills trees and vietnamese every year, and you can't blame me for having to excuse him from the dicussion. Everyone else may stay.
I've also never been able to tell someone they were out of line before. So. Mission accomplished?

[clinton]

as ole gwb says "mission accomplished!":)

[Soda]

EXACTLY! And I would like to tell you that I say it with every bit of conviction and truthfulness that our great president once did. Thank you. God bless America.

[underide]

Agent orange kills trees and vietnamese every year, and you can't blame me for having to excuse him from the dicussion.

Agent Orange is also a good 80's punk band...

Exclude AO from 'your' thread? (How do you exclude someone from a thread anyway?) You're joking right?
If not, i'd say you're a bit high on the old horse there, soda. Time to get down, maybe??

Just a 'friendly' suggestion

[Soda]

Agent Orange is also a good 80's punk band...

Exclude AO from 'your' thread? (How do you exclude someone from a thread anyway?) You're joking right?
If not, i'd say you're a bit high on the old horse there, soda. Time to get down, maybe??

Just a 'friendly' suggestion

I don't listen to punk.
Never say another insulting word about horses. Obviously you've never ridden one. Little man.
*gallops away*

[OhJoy]

Maybe that's why I'm so depressed all the time, not enough morphine in my head.

That is exactely what I believe. You may find this site interesting about why some are more prone to depression:

http://www.psycheducation.org/mechanism/MechanismIntro.htm

[SpecialGuy69]

I can't just say okay and back out of the thread. But I also dont want to start an argument/flame war. So anyways, soda your comment about you and RJ being the only ones who understand the topic pissed me off. Sorry if I overreacted.

never killed any vietnamese people, but killed plenty of trees when I was younger.

[underide]

I don't listen to punk.
Never say another insulting word about horses. Obviously you've never ridden one. Little man.
*gallops away*

See, i knew it...lol

"On your high horse overlooking the plains
You're in a place where no one remains
Shoot the moon, it's already shot
It's coming for you or. are you gone?

shoot the moon
what you got's been shot to hell..."

just playing (guitar) there, soda

Oh and i 've nothing against horses.
Especially when my Horse is BROWN, and i'm riding it into my main vein.

[Soda]

Are you actually singing to me?
Oh, and agent orange, its okay, I love you. I just don't think that many people, including me and my high horse, know very much about proteins that contain over 100 AA residue structures, or the pentapeptide structure of enkephalins. You'd have to at least google that. Either that, or I've been in a community of rocket scientists without knowing it.

[underide]

Are you actually singing to me?


No to you..To your Horse.
Also it's more of a serenade
hence the included (guitar)..

jus playing...

[Soda]

You can serenade me. But you should know I'm a guy.

[SpecialGuy69]

Are you actually singing to me?
Oh, and agent orange, its okay, I love you. I just don't think that many people, including me and my high horse, know very much about proteins that contain over 100 AA residue structures, or the pentapeptide structure of enkephalins. You'd have to at least google that. Either that, or I've been in a community of rocket scientists without knowing it.
I know about rocket fuel...

I have to read RJ's scientific posts 2-3 times to really get it all, often with wiki running in the background.

http://en.wikipedia.org/wiki/Peptide

but i'd much rather read an RJ post and actually learn something as opposed to "should I sniff this norco or shove it up my ass?" posts

[Soda]

You know about rocket fuel? Okay, I'll let you in on a little secret. I invented rocket fuel. Sounds like a lie but its true. I was in my lab one day trying to make kool aid taste better and made rocket fuel. I'm that guy. My screen name, soda, is an allusion to the rocket fuel I accidentally made.

[SpecialGuy69]

I was talking about the kind of rocket fuel that makes your face numb and sleep impossible

[Soda]

Sign me up brother, that sounds worlds more wonderful than what I was talking about. I really shouldnt though. They say its like kissing god and to never do it once. But when I look at myself im in a chair, typing, and when i look at that adress at the top of the screen it says opiophile, and i have to turn my perception back towards myself and wonder why I'm here.

[SpecialGuy69]

Are you actually singing to me?
Oh, and agent orange, its okay, I love you. I just don\'t think that many people, including me and my high horse, know very much about proteins that contain over 100 AA residue structures, or the pentapeptide structure of enkephalins. You\'d have to at least google that. Either that, or I\'ve been in a community of rocket scientists without knowing it.

actually most enkephalins have 250+ ammino acid residue structures, and are polypeptides. Dont i sound smart...

[Soda]

actually most enkephalins have 250+ ammino acid residue structures, and are polypeptides. Dont i sound smart...

Not only do you sound smart, but you're actually DISAGREEING WITH YOUR FRIEND ROBO JUNKY.

[robojunkie]

Now, now, let's not be the agent provocatuer soda. Its probably either from wiki (ie someone from TOTSE got lost and decided they knew something) or representative of some other endorphin.

Basic "rules" of our OR ligands (ie endorphins and enkephalins):

They only mean the same thing when translated. Loosely.

Endorphins, whether mu, kappa or delta ligands (beta-endorphin is, last I heard, the most potent endorphin as far as the mu receptorgoes. There is also dynorphin, but this is one of the other two OR ligands. And the biggest thing different is that endorphins are true proteins that take hours for the body to make and then more for them to slowly fold into the right tertirary structure.

Enkephalins, like Leu-E and Met-E, the ones we care about, are always included as a five amino acid chain somewhere within the amio acids (almost always over a hundred AA's sometimes up to 200). In fact some theorize that endorphins are really just reserves of our opiates and when in pain/stress/whatever, certain enzymes should lyse the endnorphin protein such that the enkephalin chain is released. Five amino acid chain equals pentapeptide. Protein equals hundreds of amino acids in a specific order AND a very specific shape. (Mad cow disease is only "infection" with misfolded proteins, ones that would be harmless if folded correctly). The term polypeptide can refer to either, though I think most tend to think of it as a protein, not a single digit peptide (peptide equals series of amino acids linked through amide bonds).

Arguing is not debating and debating and disagreeing is the basis for spreading scientific understanding, unlike say in the realm of religion, where disagreeing and debating tend to lead to lots of dead "believers"......

I remember being a kid and hearing about "Scientology", and I was like shit, a religion where you gotta prove everything you claim, nice...(grew up Catholic). Then I learned about Little Ron H, large large egos, and the obsessive overuse of copyrights. Yeah, its a fucking business, run by a business man.

[Opiyum]

Oh, yeah, mikells or barney or whoever was debating this, that powerful ~100 x morphine chem is called "Beta-endorphin". However it is neither more powerful than etorphine (~2,000-4,000 x morphine) nor carfentanyl (5,000-10,000 x morphine). Etorphine is, IMO, the Supreme Lord and Master of all "semi-synthetic" opiates, and is only 3 steps from theibane. Carfentanyl can be made the same way as fentanyl with the addition of 3 to 6 steps, depending on the methodology used. These two opioids are, to the best of my knowledge, the strongest opioids out there right now, at least with a good body of scientific research showing this to be the case definitively.

I have also read and heard a number anecdotal reports that etorphine is the most pleasurable of all opioids...
z



First off great thread....really great.

And second a slightly off topic question. Is there any record of etorphine use in a recreational manner? From what I gather if you were to dip a pin in some of this ungodly stuff and scratch yourself with it you very well could overdose. How could something like this ever be used?
I remember an old post on the forums about the use of carefentynal for riot control or something along those lines.
Point being how could you go about enjoying yourself with a chemical that could so easily kill you? yes I realize heroin kills too. hehe...

[Soda]

Arguing is totally debating.

[robojunkie]

Arguing is totally debating.

Arguing is personal, whereas debating is often similar toarguing but about a separate subject and on topic. Debating can turn into arguing, and much less often the reverse. See, I'm debating what you just said. If I started tossing ad hominems and such I'd be arguing, as well as diluting the point, whatever that may be.

Etorphine in safe doses would have to be done via serial dilution. As in say 1 gram in a liter. Then take one cc and dissolve that in say 100 ml. Now you have a solution that is 10 mikes/1 ml. The remaining concentrated solution (first one) is capped and marked with skull and crossbones, preferably labeled "cyanide" or "strychnine". No reasonable and almost no unreasonable people would choose to ingest any of those, though quite a few would "take a chance" and try some of it or steal it or whatever. One thing is that it shouldn't be kept as a powder just due to the fact that there are too many fucks who don't know what they are doing and too many sociopaths who don't care. When one person is both of those, you start hearing about "fill in the blank/etorphine" OD's in whatever city.

[Soda]

Stop debating me.

[SpecialGuy69]

m rubber your glue...

RJ is right- I just misread some shit on wiki and put it up trying to sound smart. I never claimed it was true, never assume anything I post is true. RJ- is there any real way to \"use\" peptides like opiates? Like to order up a batch from some bioengineeing place and sniff/IV/eat them? Or do they have to be produced in situ in the brain to have any effects?

[Soda]

Agent Orange, no man, for any considerable period, can wear one face to himself, and another to the multitude, without finally getting bewildered as to which may be true...

[SpecialGuy69]

Agent Orange, no man, for any considerable period, can wear one face to himself, and another to the multitude, without finally getting bewildered as to which may be true...
what did you say about my face?

[robojunkie]

m rubber your glue...

RJ is right- I just misread some shit on wiki and put it up trying to sound smart. I never claimed it was true, never assume anything I post is true. RJ- is there any real way to \"use\" peptides like opiates? Like to order up a batch from some bioengineeing place and sniff/IV/eat them? Or do they have to be produced in situ in the brain to have any effects?

Only if you are prepared to have a spinal set up. Or possibly an epidural. So, other than the last sentence, this is the only way you'll get'em there. Peptides are literally food, like meat or nuts, high in protein, and the "peptidase" enzymes will break those babies down into moderately useless amino acids. Useless for drugs that is, unless of course you're talkin' tryptophan, which can be darboxylated and methylated and...dum dum duhhhh...DMT.


Agent Orange, no man, for any considerable period, can wear one face to himself, and another to the multitude, without finally getting bewildered as to which may be true...

Huh? I'm not sure I follow, are you trippin' out soda? You gotta lot of these random one line posts on inventing rocket fuel, debating and not debating and arguing, then this one. I'll assume you are referring to why he posted the wiki thing? Hopefully not something else, that would not be permissble. If this makes no sense, don't worry about it, OK. I'm just nippin' any potentialities in the bud.

And you didn't invent rocket fuel. I did. Or at least the type I use. But I'd be willing to debate and argue with you as to whose rocket fuel is better. Mine can push rockets past the escape velocity and push me past sanity velocity. Made from a secret patented element called Robonium, Rm. Its one of those metalloid elements, its liquid, and its the only known element that can transmute sponstaneously into etorphine while maintaining its appearance to all but me as a liquid metal like mercury, only better, because it appears as a brilliant gold-like liquid metal. It is also resistant to all known acids and combinations thereof and even the atomic number is unknown because it is in a constant state of flux, gaining and losing nucleons so fast to and from higher dimensions that it only really has an average atomic number and weight.

And only I can make it, and it is only made through my telekinetic/telegenetic powers. Yes, telegenetic, I can make shit with my mind. Think about it.

[underide]

Huh? I'm not sure I follow, are you trippin' out soda?

And you didn't invent rocket fuel. I did. Or at least the type I use. But I'd be willing to debate and argue with you as to whose rocket fuel is better. Mine can push rockets past the escape velocity and push me past sanity velocity. Made from a secret patented element called Robonium, Rm. Its one of those metalloid elements, its liquid, and its the only known element that can transmute sponstaneously into etorphine while maintaining its appearance to all but me as a liquid metal like mercury, only better, because it appears as a brilliant gold-like liquid metal. It is also resistant to all known acids and combinations thereof and even the atomic number is unknown because it is in a constant state of flux, gaining and losing nucleons so fast to and from higher dimensions that it only really has an average atomic number and weight.

And only I can make it, and it is only made through my telekinetic/telegenetic powers. Yes, telegenetic, I can make shit with my mind. Think about it.




Why, Tis' you the one who's 'tripping out', Robo....

lol...it's all good though...better that than having no imagination.
and who am i to judge anyway

[Soda]

I hate to see you in emotional pain robo.
Whenever I feel stressed I turn up the bass, roll down the windows, play this:
http://youtube.com/watch?v=b34U3-CutuU

...White Mag rims, red rubber tires,
Chain, frame, pegs, grips, shift to my supplier/
Dope man attire, gimme bout an hour/
And I'll have it clicking, ticking, gliding, flying like McGuyver/
I'm a Murder Club, dope pedal rider/
Nigel said I'm good to get that ink on my bicep/
I gets, busy as a bee on my bike grips/
If I catwalk this, I walk, I can fly this/

[SpecialGuy69]

robonium is real. you can smoke it off foil. it also catalyzes birch reactions with aqua ammonia and makes vinegar into acetic anhydrate

[Soda]

I just thought id do a little rap. I was serenading robo and his knowlege. Id love to sit down with him and pick his brains.

[poonwhalla]

isn't this one a little old to be voting on without adding to???

[insanesteveo]

my thoughts on tolerance to morphine if its produced inside the body. there are a couple ways to go.

endo morphine and morphine vary slightly and therefore affect receptors differently. if thats the case, it explains tolerance to morphine.

both are the exact same, but the body keeps the morphine it produces somewhere in the body and only releases it when needed. ie, when you are in pain.

both are the exact same and your body DOES build a tolerance to it, but it just isnt that large and doesnt grow as fast. your body isnt constantly chasing a high. but when your body does have a lull in production you actually do w/d a bit, just not enough to attribute it to opiate w/d. i believe jacky stated this in another thread, about runners who feel worse on the days they dont run. well those would be the "lull" days.


now, i personally think its one of the second two. but that raises another question if its the last one. if the brain has it all the time, then doesnt for awhile so you go into a slight w/d, wouldnt your brain produce more? i assume it would as not to harm itself. of course producing chemicals in the body is a slow process and dependent on how nutritous and healthy you are.

[Soda]

my thoughts on tolerance to morphine if its produced inside the body. there are a couple ways to go.

endo morphine and morphine vary slightly and therefore affect receptors differently. if thats the case, it explains tolerance to morphine.

both are the exact same, but the body keeps the morphine it produces somewhere in the body and only releases it when needed. ie, when you are in pain.

both are the exact same and your body DOES build a tolerance to it, but it just isnt that large and doesnt grow as fast. your body isnt constantly chasing a high. but when your body does have a lull in production you actually do w/d a bit, just not enough to attribute it to opiate w/d. i believe jacky stated this in another thread, about runners who feel worse on the days they dont run. well those would be the "lull" days.


now, i personally think its one of the second two. but that raises another question if its the last one. if the brain has it all the time, then doesnt for awhile so you go into a slight w/d, wouldnt your brain produce more? i assume it would as not to harm itself. of course producing chemicals in the body is a slow process and dependent on how nutritous and healthy you are.

First of all, to the poster before you, this thread is indeed old and I have no objections to putting the old girl down, lest she be smitten by the rabies or take up bandwidth.
My question to you is what you mean when you say "its the second of the two," because that made no sense. Secondly, do you truly feel people who use no opiates of any sort go through "slight w/ds?" If so, why do you think the brain would "produce more?" Also, what harm are you talking about? These are my questions that will clarify your opinion.

[Paregoric Kid]

there is also endogenous codeine in your brain as well. some of the endorphin and enkephalin reuptake inhibitors may work as antidepressants and pain killers. not enough research has been done to determine what the average level of endogenous opiates, endorphins, enkephalins, etc is in a normal person compared to a person who is: addicted, depressed, in pain, etc. and what low levels mean and the effects and side effects of using precursors and/or reuptake inhibitors. it probably does happen, could be an issue in a lot of different diseases, more research definitely needs to be done. obviously there would be implications for diseases involving pain and the issue of tolerance, dependence, withdrawal, etc. but I think one area that could benefit from research into this is depression. I think many types of depression might be attributed in some way to the opioid system. too much attention is being paid to serotonin and norepinephrine and not enough into the opioid and dopamine systems.

[Spork]

]

both are the exact same and your body DOES build a tolerance to it, but it just isnt that large and doesnt grow as fast. your body isnt constantly chasing a high. but when your body does have a lull in production you actually do w/d a bit, just not enough to attribute it to opiate w/d. i believe jacky stated this in another thread, about runners who feel worse on the days they dont run. well those would be the "lull" days.


Before I ever used opioids I remember similarities between natural emotional/mental highs and lows, with artificial opioid highs and withdrawal.

Similar physical feelings with similar mindsets, I guess, always makes me think about endogenous ENDOrphins.

[pain-patient]

Fixed. And, based on this study, apparently demonstrating fairly conclusive its presence in mammalian (incl. human) brains, it would seem reasonable like any other small molecule neurochemical deficiency, that a lower than average endogenous morphine level could exist in humans. This would be a good correlation with evidence that addictive behavior patterns have a very significant genetic/hereditary component, which implies some sort of chemical make up difference in those genetically predisposed. However it would also be relevant to know how important (and how much) endo-morphine is in the various neurological processes, especially in relation to endorphins/enkephalins. Another interesting question(s):

1) If we make endorphins/enkephalins and all the opioid receptors have endogenous polypeptide ligands, why do we need/have natural morphine (biologically speaking, of course we "need" it)?

2) How the hell would the receptor differentiate between morphine and morphine? If the same structure, well, its the same structure. There's no magical genetic "tag" on it to trick the receptor.

However, Q2 could be related to potential research into what processes tell the neuron to grow more receptors/induce endocytosis of receptors when in presence of morphine. Like is there a certain small level naturally present that the brain "expects" and so doesn't adapt? What if the endo-morphine was blocked? Would an opposite response, vis a vis tolerance and withdrawal, occur? Anti-tolerance? Remove the blocker and we "withdraw" by getting excessively opiated? Wow...

What I'm trying to say it that where the reticuline is mentioned and its potential to serve as a morphine bioprecursor, if tolerance to our own doesn't occur their must be some simultaneous (to endo-morphine release) process that inhibits the development of opioid tolerance. Find the transmitters/enzymes in this process, then you have a chance at discovering the keys to the development of tolerance and the potential to develop analogues to prevent it with exo-morphine and other opiates. I would love to know the answer to question 2, because if it is different somehow, this would breakthrough I've been waiting for, as far as pharm research goes.

Imagine, being able to trick the brain into thinking your opiates are really produced internally and naturally tolerated, without induction of the tolerance/addiction process!

Robo ---

Good to see you posting and I hope you're okay. That said, I, too, am confused by something in the original post which you expanded upon, to wit: reticuline. I did a Google search on the term and got this Wiki site -- http://en.wikipedia.org/wiki/Reticuline_oxidase. From reading it, it's apparent that formation of alkaloids is involved, but I'm still at a loss to picture how this works.....Could please elaborate even more far those of us lacking your considerable biochemical acumen?

Thanks,

M

[pain-patient]

You have a scientific mind jacky, havent seen this side of you before. Sort of makes you think, why poppies?
Why does this plant have such a hardon for producing morphine? Makes you also wonder what else the morphine family of narcotics are good for. We all know plants don't have a brain or a central nervous system, but they wouldn't produce these alkaloids for no reason.
We know so much about what is produced in our body that we ISOLATE it, just like we did with morphine and such.
As you know, "vitamins" and "antioxidants" (found in every pharmacy) are just products of our own very human bodies. Just like the opium poppy, we are machines that create chemicals. It's funny, I think.

Yet when we look at the opium poppy, and see all the drugs that have been made from it, we don't stop for a second to think about the poor little poppy itself. What are chemicals like morphine and thebaine actually FOR? Why are they made by such a weird little plant?
Sure, they produce pain relief in humans, but do plants have pain? Do they need relief? You know. It's a question that should be answered, but hasn't.
Not only that, but now that we know morphine is made in other plants it makes us wonder even more why morphine even exists. It also reminds us of one almost eerie fact...opiates WERE NEVER INVENTED. Almost makes you open your bible.

Soda --

You should commence to start answering those questions and you will be the nest Michael Pollan........:cool:

M

[pain-patient]

The quote about morphine and morphine was intentionally sarcastic. If we truly have endogenously formed morphine (and not "morphine like" whatever) there is a reasonable assumption we don't become tolerant to it, as this would be counterproductive to the purpose it would serve. That quote was an attempt at asking the rhetorical question: "How does the brain (or anything) tell poppy morphine from homo sapien morphine? Well, it either can't, and this means tolerance won't develop to a limited samll amount, or much better, it can, but since the molecules are identical (morphine is morphine) how can the mu receptor "tell" whether or not to adapt? Well here's the answer: It couldn't. OK, then one would ask, how come you don't get "addicted" to your own morphine, slowly making more and more? Well my theory would be, and has been for awhile, that there are intracellular processes that correspond to the release of natural endorphins and "endo-morphine" that essentially must let the downstream neuron know to "expect" morphine and not initiate the development of tolerance.

Think about it, you take exo-morphine and your brain does not produce or expect it (in fact physiologically speaking, it doesn't want it either), the brain's response is to re-establish homeostasis, which is just body equilibrium, by inducing tolerance to the "imbalance" caused by morphine. Therefore if we have naturally occurring morphine in our brains, and we don't become tolerant to it, it seems apparent to me that either A) there is a simultaneous release of another transmitter from the morphine releasing cell (or one near it) that is directed towards the cell with the MOR, and this transmitter is what would be "informing" the next cell that it should be getting the M. Therefore, that transmitter initiates some process (or inhibits some process) related to the adaptation of the receptor count to morphine concentration or B) similar to A, the release of morphine also stimulates release of another NT to another cell, which then communicates with the MOR containing cell, again inhibiting the tolerance development

Now, the really really important part for us junkies: If the M releasing cell is also involved in carrying an "artificial vs natural" message to the receiver cell, ie one that only occurs on release of morphine from a cell, this is prima facie evidence that there exists in us a biochemical pathway directly relating opiate source to the tolerance phenomena, and that this pathway initiates a process within the receiving neuron that completely inhibits the development or even initiation of the tolerance process.

Think about it, this could, in theory lead to a pill that we all could take at whatever required frequency on a regular basis (like an AD), but this then tricks the receiving (MOR) cell into thinking the copious amounts of morphine/oxymorphone/fentanyl/etorphine on its MORs are really just NTs released from the upstream cell.

Fucking amazing if true and possible. So, the initial question, answered, is this: the brain, neurons nor anything else can tell the "mann (bio)made" and the "man (farm/chem) made" apart, without some requisition sheet or receipt that comes with the biomorph (ie the sheet/receipt is that second NT). The injected (it better be or I'm pressing charges for violation of basic Opiolaw!) morphine, not coming from the first cell, would also not have a corresponding "no tolerance" signal. Therefore, if the brain can differentiate "morphine from morphine" than there is an extremely good chance that this pathway's receptor can be mapped, the enogenous NT/ligand discovered, SAR's accomplished that a range of molecules could be prepared with anti-Tollerancene activity. (Yes, the NT is called tollerancene, kidding).

Just fucking imagine this, that second pathway of neural communication can lead directly to the deveopment of a daily pill that could quite possibly block the development of tolerance in us junkies, and also quite possibly block the loss of tolerance on kicking. But after one last shitty kick, we wouldn't have to worry about that anymore, huh?!?!?!

Robo ---

Wow! This makes a lot of sense. Why, though, do you think the anti-tolerance signal must come from the pre-synaptic neuron and affect the post-synaptic one? Is it not possible that the signaling molecule comes from somewhere else, perhaps being a segment leftover from the production or cleaving of pro-opio-melano-cortin? I have always wondered why endorphins and enkephalins we've known about for a long time do not induce tolerance? Would your theory or some variant thereof account for that as well?

Damn, I miss you on here buddy.:D You and rescorcinol contributed the best posts relating to biochemical aspects of opioi-dom and it seems he has vanished and we don't get your wisdom too frequently these days, either.

Hope that inactivity ceases!:cool:

Best,

M

[pain-patient]

Oh, yeah, mikells or barney or whoever was debating this, that powerful ~100 x morphine chem is called "Beta-endorphin". However it is neither more powerful than etorphine (~2,000-4,000 x morphine) nor carfentanyl (5,000-10,000 x morphine). Etorphine is, IMO, the Supreme Lord and Master of all "semi-synthetic" opiates, and is only 3 steps from theibane. Carfentanyl can be made the same way as fentanyl with the addition of 3 to 6 steps, depending on the methodology used. These two opioids are, to the best of my knowledge, the strongest opioids out there right now, at least with a good body of scientific research showing this to be the case definitively.

I have also read and heard a number anecdotal reports that etorphine is the most pleasurable of all opioids...
z

Robo --

I would like to get those reports about etorphine and pleasure, but would I have to talk to elephants to do so?:rolleyes:

[pain-patient]

Only if you are prepared to have a spinal set up. Or possibly an epidural. So, other than the last sentence, this is the only way you'll get'em there. Peptides are literally food, like meat or nuts, high in protein, and the "peptidase" enzymes will break those babies down into moderately useless amino acids. Useless for drugs that is, unless of course you're talkin' tryptophan, which can be darboxylated and methylated and...dum dum duhhhh...DMT.



Huh? I'm not sure I follow, are you trippin' out soda? You gotta lot of these random one line posts on inventing rocket fuel, debating and not debating and arguing, then this one. I'll assume you are referring to why he posted the wiki thing? Hopefully not something else, that would not be permissble. If this makes no sense, don't worry about it, OK. I'm just nippin' any potentialities in the bud.

And you didn't invent rocket fuel. I did. Or at least the type I use. But I'd be willing to debate and argue with you as to whose rocket fuel is better. Mine can push rockets past the escape velocity and push me past sanity velocity. Made from a secret patented element called Robonium, Rm. Its one of those metalloid elements, its liquid, and its the only known element that can transmute sponstaneously into etorphine while maintaining its appearance to all but me as a liquid metal like mercury, only better, because it appears as a brilliant gold-like liquid metal. It is also resistant to all known acids and combinations thereof and even the atomic number is unknown because it is in a constant state of flux, gaining and losing nucleons so fast to and from higher dimensions that it only really has an average atomic number and weight.

And only I can make it, and it is only made through my telekinetic/telegenetic powers. Yes, telegenetic, I can make shit with my mind. Think about it.

Did I say that I missed you for your erudite comprehension of biochemistry? I should have said I missed your humor:D. Hell, Robo, I miss both, so post more often, dude, please:cool:?

[Oakleyskier]

holy quadruple post +1 batman.