Zen, and the opiated brain

[jacky]

I am going to start posting different data and statements from a scientist/zen researcher named James H Austin....
this person is a teacher and a neurosurgeon as well as zen practitioner...

His book "zen and the brain" is a great,huge, and suprisingly readable multi-layered approach to mind state studies, both pharmacological and ontological.

he had written a few chapters that directly relate to exogenous and endogenous opiates/opioids and suprising facts about pharmacology that might make a few people think twice when they consider that opiates should not be used during meditation.
among other things.

I am sure that James H Ausin himself doesnt suggest a person use opiates in their practise as a novel approach, and I am sure as a doctor and as a Zen pracitioner that he wouldnt suggest that a person who is on pain meds forgo their medication just to meditate.
some of the facts he relates, and opinions on the action of opiates/endorphins as a support of cognition are quite the opposite of what most people would think.

here is his quote from the last paragraph of his chapters on opiates and cognition..

" In summary, the brain's own opioids have brief but striking properties. They are poised to slow respirations,block suffering, enter into novel and positive affective responses,confer salience, and act in many other intriguing ways that bear DIRECTLY on Zen experience." -James H Austin page 223 paragraph3 (Zen and the brain)


after reading his book, and a few others, I realized that all people are opiated at all times, cognition and mobility would be slaughtered if all endorphins/endogenous opiates were somehow eliminated from the body, and soon death would follow.

it is a pretrans fallacy that the judgemental anti drug zealots fall into when they consider a person a junky and consider themselves (sometimes virginally) clean of opiates, all humans and mammals, and most other life forms for that matter, rely on opiates as much a part of existance as any other biological support system. a person will test positive for opiates at some level at all times.

[Hammilton]

after reading his book, and a few others, I realized that all people are opiated at all times, cognition and mobility would be slaughtered if all endorphins/endogenous opiates were somehow eliminated from the body, and soon death would follow.

That's not entirely true. People function on Nalterexone all the time.

[Raz]

I am going to start posting different data and statements from a scientist/zen researcher named James H Austin....
this person is a teacher and a neurosurgeon as well as zen practitioner...

His book "zen and the brain" is a great,huge, and suprisingly readable multi-layered approach to mind state studies, both pharmacological and ontological.

he had written a few chapters that directly relate to exogenous and endogenous opiates/opioids and suprising facts about pharmacology that might make a few people think twice when they consider that opiates should not be used during meditation.
among other things.

I am sure that James H Ausin himself doesnt suggest a person use opiates in their practise as a novel approach, and I am sure as a doctor and as a Zen pracitioner that he wouldnt suggest that a person who is on pain meds forgo their medication just to meditate.
some of the facts he relates, and opinions on the action of opiates/endorphins as a support of cognition are quite the opposite of what most people would think.

here is his quote from the last paragraph of his chapters on opiates and cognition..

" In summary, the brain's own opioids have brief but striking properties. They are poised to slow respirations,block suffering, enter into novel and positive affective responses,confer salience, and act in many other intriguing ways that bear DIRECTLY on Zen experience." -James H Austin page 223 paragraph3 (Zen and the brain)


after reading his book, and a few others, I realized that all people are opiated at all times, cognition and mobility would be slaughtered if all endorphins/endogenous opiates were somehow eliminated from the body, and soon death would follow.

it is a pretrans fallacy that the judgemental anti drug zealots fall into when they consider a person a junky and consider themselves (sometimes virginally) clean of opiates, all humans and mammals, and most other life forms for that matter, rely on opiates as much a part of existance as any other biological support system. a person will test positive for opiates at some level at all times.
^^^so without consumin any "drugs" A person will test positive for opi's??

[jacky]

sure, they function on naltrexone, but that doesnt mean that the bodys endorphin function is shut down all over the body, there are opiate receptors all over the human/animal body...

and naltrexone doesnt block opiates all the time anyway, I used dope on naltrexone, and felt it after a few hours just fine, it only took 2-3 times my normal amount, a 40$ piece got me high no problem.

all I am saying really is that opioid/opiate endorphins play a large part of our minute to minute consiousness, they play hormonal roles, not just pain perception augmentation.
if all the bodys opiate receptors shut down, you would not be in a state of mind and body to do anything but suffer...you would not be able to recall, memorize, or basically walk without major disfunction.

experience forced withdrawl and then tell me about it, ha ha. you wouldnt last long in that state, even under medical supervision.
and that is only shutting down the receptors in the brain for the most part...and bowel tract.
SHUDDER.

[Raz]

sure, they function on naltrexone, but that doesnt mean that the bodys endorphin function is shut down all over the body, there are opiate receptors all over the human/animal body...

and naltrexone doesnt block opiates all the time anyway, I used dope on naltrexone, and felt it after a few hours just fine, it only took 2-3 times my normal amount, a 40$ piece got me high no problem.

all I am saying really is that opioid/opiate endorphins play a large part of our minute to minute consiousness, they play hormonal roles, not just pain perception augmentation.
if all the bodys opiate receptors shut down, you would not be in a state of mind and body to do anything but suffer...you would not be able to recall, memorize, or basically walk without major disfunction.

experience forced withdrawl and then tell me about it, ha ha. you wouldnt last long in that state, even under medical supervision.
and that is only shutting down the receptors in the brain for the most part...and bowel tract.
SHUDDER.
From wat i understand (probably nish) you are sayin we have receptors all over the body.So what is naltrexone targettin? I thought this naltrexone blocked all opi's in your brain..
This may seem dumb ?? but what is the point of drug tests, or are they measurin the level of opi's in ya?Like evrybody has opi's in them but drug users have significant higher levels..Eg say level 10 opi, is a non user but level 100 is a drug user.
I am just tryin to get a better understandin of all this.So i am only askin for knowlegde jacky, not tryin to pic your thread apart, just want to learn.And at the mo would be grateful if you could explain this a bit more...Raz
Ps xperienced forced w/d in jail after chasin 3.5 g habit.It was my 1st xperience of W/D.Shall i say i didnt like it........

[robojunkie]

Correct me if I'm wrong here (Jacky), but I believe he is referring to the overall status of the neurosystem and its requirement of natural endogenous opioids, such as the endorphins and their "lysed" active peptide portions, enkephalins. And these hormones, or more accurately neurohormonal transmitters, have a profound effect on virtually all areas of human functioning. I can't cite sources off hand, but I have no doubt from a number of things I've read about this, that endo-opioids are involved in areas ranging from the obvious like pain perception and joy and euphoria to learning and memory as well as immune function and other health aspects.

Simply ingesting naltrexone, which has a MOR affinity in the range of morphine-like opiates, can't come close to blocking all natural opioids. Even diprenorphine, the super-antagonist that is to etorphine what naloxone is to oxymorphone, wouldn't be capable of truly blocking every MOR from the day to day non-euphoric non-analgesic activities and processes that the endogenous opioids. But even naltrexone appears to have all kinds of deleterious effects on their functioning, if all the various testimonials as to how much it sucks to be on and how it kills all happiness and desire are true, and I believe they are as so many junkies who have tried it seem to nearly always agree on the awful state that it produces well after the withdrawal is over.

Oh and Raz, a non-user would not test positive for "exogenous" opioids such as heroin or morphine or oxymorphone or any of the others, however they would all test positive for the various endorphins and enkephalins, were such a straightforward piss test type thing available for these. The major difference, chemically speaking, between the ones we bang and the ones we produce (haha, not in a lab, in our bodies and brains, that is) is that virtually all, if not all, exogenous opioids, whether naturally occuring, semi-synthetic or sythetic, are all alkaloids, as well as not being oligopeptides. Endo-opioids all have in common the trait of being oligo- or polypeptides, with enkephalins having as little as 5 amino acids with the ubiquitous amide linkage, absent in virtually all exogenous opioids, and as many as hundreds of amino acids, with specific sequences behaving as "active portions" when in their full tertiary structure (meaning the way the 100 some odd amide linkages with their individual groups, like leucine, methionine, etc, wrap around and form a certain overall shape so that the groups align in a conformation that will fit a given receptor). So, because of this rather huge chemical difference, "straights" will test (using the current type of drug tests available) negative for opiates, but that would be the purpose of the tests, to "bust" those who are taking exogenous opioids, as well as the fact that if it were otherwise, virtually everyone would test positive.

[Raz]

Correct me if I'm wrong here (Jacky), but I believe he is referring to the overall status of the neurosystem and its requirement of natural endogenous opioids, such as the endorphins and their "lysed" active peptide portions, enkephalins. And these hormones, or more accurately neurohormonal transmitters, have a profound effect on virtually all areas of human functioning. I can't cite sources off hand, but I have no doubt from a number of things I've read about this, that endo-opioids are involved in areas ranging from the obvious like pain perception and joy and euphoria to learning and memory as well as immune function and other health aspects.

Simply ingesting naltrexone, which has a MOR affinity in the range of morphine-like opiates, can't come close to blocking all natural opioids. Even diprenorphine, the super-antagonist that is to etorphine what naloxone is to oxymorphone, wouldn't be capable of truly blocking every MOR from the day to day non-euphoric non-analgesic activities and processes that the endogenous opioids. But even naltrexone appears to have all kinds of deleterious effects on their functioning, if all the various testimonials as to how much it sucks to be on and how it kills all happiness and desire are true, and I believe they are as so many junkies who have tried it seem to nearly always agree on the awful state that it produces well after the withdrawal is over.

Oh and Raz, a non-user would not test positive for "exogenous" opioids such as heroin or morphine or oxymorphone or any of the others, however they would all test positive for the various endorphins and enkephalins, were such a straightforward piss test type thing available for these. The major difference, chemically speaking, between the ones we bang and the ones we produce (haha, not in a lab, in our bodies and brains, that is) is that virtually all, if not all, exogenous opioids, whether naturally occuring, semi-synthetic or sythetic, are all alkaloids, as well as not being oligopeptides. Endo-opioids all have in common the trait of being oligo- or polypeptides, with enkephalins having as little as 5 amino acids with the ubiquitous amide linkage, absent in virtually all exogenous opioids, and as many as hundreds of amino acids, with specific sequences behaving as "active portions" when in their full tertiary structure (meaning the way the 100 some odd amide linkages with their individual groups, like leucine, methionine, etc, wrap around and form a certain overall shape so that the groups align in a conformation that will fit a given receptor). So, because of this rather huge chemical difference, "straights" will test (using the current type of drug tests available) negative for opiates, but that would be the purpose of the tests, to "bust" those who are taking exogenous opioids, as well as the fact that if it were otherwise, virtually everyone would test positive.

Aha, the" evil genuis "makes it clear once again..!So the terms i have to differntiate and recognise are"exogenous opiods" and endogenous opiods..Aha now i see.We have naturally produced opiods, hormonal receptors an stuff, which are opiates per say,but not druggy opiates..I think i get it now..
Thank you.And jacky's point is that if all endogenous opiods were removed from non druggies, that they too would experience a cluck,W/D...If i understand all this correctly.Do i have the right take on this, MR evil junkie scientist?..
Thanks for your help...Raz

[scarlettt]

Hmmm... this is interesting.

Just curious, but what are you guys thoughts on a person who is innately attracted to opiates?

Do you believe that is because they may lack less of these natural opioids.. and therefore crave them more intensly than someone who for example.. had tried opiates but does not feel a compulsion to use them again and again?

[Raz]

^^^ a lot of guys attracted to opi's have been sayin something about a natural endorpin deficiency....

[robojunkie]

Hmmm... this is interesting.

Just curious, but what are you guys thoughts on a person who is innately attracted to opiates?

Do you believe that is because they may lack less of these natural opioids.. and therefore crave them more intensly than someone who for example.. had tried opiates but does not feel a compulsion to use them again and again?

Well scarlett, I know that there is a strong correlation between being the child of an "addict/alcoholic" and developing this as well as an adult. I recall hearing 10 x the chance of an average person if 1 parent, something like 400 x the chance if both, and since I believe these statistics have been repeatedly verified in studies, I would assume there is a genetic component here. Obviously some of the correlation is due to the environment one grows up in, but that certainly does not cover it all. Personally I don't see anything unreasonable about the potential for an "endorphin deficiency syndrome" or some genetic trait that equals that in effect, ie gives some a "natural" susceptibility to developing that junky-esque love for opiates. It is a well demonstrated fact that different individuals will respond to the same painful stimuli with a wide range of subjective intensity, as in some would say "Oh, I rank that as a 3" and others that would say "Fuck, I can't take this pain anymore! It's like at least an 8!". Naturally this must be the result of differences in the nociceptive (pain interpreting) system, and therefore its modulating system, the opiate receptors/ligands. So in short, I do believe that many junkies have a certain degree of inborn tendency to quickly develop opiophilia with very little experience of opiates (I'm talking the psychological aspect) whereas others may take much longer or never really become true opiophiles.

And, yes raz, I believe that if it were possible to literally block every single opiate receptor of every type everywhere, that the unlucky individual would experience a horrific state of dysphoria that would likely resemble withdrawal in many ways, but would also quite possibly have additional dysphoric effects involving health, memory, learning, anhedonia, loss of desire to do anything once enjoyable and a general all encompassing state of malaise. For example, dopamine antagonists (antipsychotics, like haldol or thiothixene) are known to produce a side effect (I've experienced it when put in an adolescent psych/detox/rehab ward at some typical 80's/90's "we'll fix you until your insurance runs out" type places) called akisthesia, and I would have to rate it as the most uncomfortable effect of a drug, other than strong opiate withdrawal, that I've ever experienced. And what made it worse was that I had no idea of its source at the time as it often comes on many hours after being hit with these "meds". In some ways it is similar to lighter withdrawal where one cannot sit still, there is an undefinable sense of dysphoria and abstract pain throughout the chest and back and gut, as well as a sinking sense of utter despair. And this is the result of blocking only some of the dopamine receptors, never mind the plethora of "downstream" effects that opiates have.

Endo-opioids (and the drugs, too) are unlike the "primary" neurotransmitters like dopamine or serotonin in that their effects are the combination of the effects they incur on the immediate receiving cell as well as number of downstream receptors of different types, probably most importantly the dopamine system. So, if haldol induced akisthesia, and opiate withdrawal, are any indication of what total massive Opiate Receptor blockade would feel like, it must be a special state of hell reserved for the living who will soon wish to neither live nor feel.

PS: Nice avatar scarlett, I like the "one eye/half face" thing, just something mysterious and trance-inducing about it. It always catches me when I scroll down the page.

[jacky]

experienced forced withdrawl in jail, ??????????

you mean you were forced to withdrawl, but not given an opiate antagonist?

to clarify my point what I meant was that I had experienced "forced withdrawl" from taking an opiate antagonist/agonist(buprenorphine/naloxone) before I should have, I was switching from illict opiates, to buprenorphine, and I didnt wait long enough.
the effect of the bup and naloxone I suppose , of kicking opiates off of your receptors, is VERY VERY fucking painful experience.
I have experienced this a few times, and had to help a few other people out who did the same thing.

this type of forced withdrawl is a 1000% x more painful that just regular heroin withdrawl, its scrunched into a few hours (if your lucky) and you are completely debiliated.


I am not an expert on pharmacology, but from what I have gathered from reading research, we are just starting to learn the vast pharmacology of the opiate receptors, and now all the new subtype receptors.

read into this book by James H Austin, and you will see, that standard opiates that the body produces as endogenous hormones, INCLUDING morphine , are used by the body and brain for different functions.

I suspect that heroin addiction and other opiate addictions lowers production of endogenous opiates, but I doubt the body stops all opioid neurotransmitter production, even when your addicted for years. for the most part, a persons body returns to normal activity when a tolerance to opiates is achieved.
that is why a doctor who is precscribing pain meds can give you license to drive after you display tolerance.

I know your not picking my post apart, and there is no harm done , nor any ill will meant...

I just think that naltrexone is not a good model for figuring out how the endogenous opiate system works, first place, it doesntt do what its marketed for in all people,
it seems like naltrexone has more inhibition of psychedelics effects than it does the opiates!!
(personal and freinds experiences)
perhaps the opiate receptors are involved with some stages of psychedelics effects like I proposed awhile ago?
how could euporia not involve the opiate receptors?

anyway, there is alot of room for arguments in this area of science...
the opiate receptors werent discovered till the 1970's.
and we are learning more and more things about endogenous opiates every year.

take care, and if you find some info that contradicts my opinions by all means lay it on me man!

[stvip]

Jacky:
Try searching for "opioid receptor knockout". You might be surprised. (if the term isn't familiar, learn about "gene knockout" first)
The interpretation of these results isn't straight-forward, though. (Biology rarely is)
As for receptor subtype: they might not be what they seem. Newer research suggests they're actually various dimerization of the three opioid receptors, or possibly even other types of linkages.
(also interesting research about the connection between receptor oligomerization and tolerance)

Robojunkie: some of your statements are incorrect. For example: enkephalins are not the active moiety of endorphins, they're different chemicals altogether (and apparently, more important for basal hedonistic state, i.e: general "natural" "mood", taking into consideration how problematic it is to apply neuropsychiatric results in animals to humans). Morphine is an endogenously produced opioid. Also, I don't see why pumping an organism full of a very high affinity antagonist would not serve to block all ("all" for practical purposes, since one does not speak in absolutes and certainties when in atomic scales) receptors.

[Hammilton]

There's very, very little evidence that morphine is endogenously produced. The research hasn't been duplicated, and I don't think it's all that convincing until then. And even then it hasn't been shown to occur under natural conditions, in a few cell lines in petri dishes, heavily fed precursor amino acids.

It's quite possible that it is produced endogenously, but to date there just hasn't been a study to replicate it.

For one, there aren't opioid receptors all over the body, they're concentrated in two locations: the gut, the CNS. I'm certain there are some located in other locations, but they're decidedly few and far between.

There's no reason that any antagonist with a high enough affinity for the u-receptor wouldn't be able to block every receptor in the body. I mean "every" as in "almost every" since there's no way you could have one in the receptor every time, constantly. When they dissociate, there's bound to be a short time before another molecule comes and fills it again.

You're not going to experience what we're familiar with as opiate withdrawal from usage of these drugs, though. You're bound to experience some effects, but it's not the same.

The reason you can get high on naltrexone is because it's affinity isn't that high. Eventually you'll overpower it with the morphine. That's not true of antagonists with much higher affinity.

[Opiyum]

There's very, very little evidence that morphine is endogenously produced.

If Morphine was produced Endogenously why would we not develop a tolerance to the natural morphine but when we take morphine Exog-....the outside pill shaped kind we do? If it were produced naturally, and lets say any and all opiates that we find in nature didn't exist, wouldn't this mean that throughout a person's lifetime we would progressivley feel less and less joy. That is unless the body automatically upped the dose.


I realized that all people are opiated at all times, cognition and mobility would be slaughtered if all endorphins/endogenous opiates were somehow eliminated from the body, and soon death would follow.

Is this something he talks about a lot in the book? I remember you recommending this book to me a long time ago but it must have slipped my mind. I think I will have to get it this time though I've never in my life ever even attempted to meditate and that is something I have been thinking about remedying.


My only question, which I imagine there is no answer to, is why is it so necessary for the body to experience pain? I realize it's a defense mechanism so people kill themselves by standing in a fire or jumping into oncoming traffic but one thing I never understood was, for instance, say I slam my toe into a wall. Why does that sensation of pain have to linger for such a long period of time. Afterall I realize what I did and I know not to do it again. Or say I break my leg. Why is the pain a person experiences in the following weeks necessary. Does the brain not recognize the fact that the leg is now in a brace or cast and is being taken care of. I mean....I know my leg is broke. I know I need to take it easy on the leg. So why do I need the constant reminder?

It may be a stupid slightly off topic question but I wonder if anyone can enlighten me in anyway.


Great stuff as always Jacky. Your the man (even though I thought you were a women for a few months back when I first joind O-phile).

Interesting stuff as always. I can't wait to read more of James H Austins' work.

[scarlettt]

he had written a few chapters that directly relate to exogenous and endogenous opiates/opioids and suprising facts about pharmacology that might make a few people think twice when they consider that opiates should not be used during meditation.




This is a fascinating thread topic.
I've always found that meditating (or any attempt at seeking a deeper state) was next to impossible for me while on a drug, be it opiate or whatever, unless said drug is a hallucinogenic. And even then... the deeper state which arises from the psychedelic is more of a manic form of deeper cognition... not the kind which arises from "sober" meditating and/or attempts at visualization.

That's just me though, maybe those more skilled at it would be more successful. I plan to look into this book.



p.s. - Thanks, Robojunkie, I could say the same for yours. :-)

[stvip]

The research hasn't been duplicated, and I don't think it's all that convincing until then.

Why are you pretending to be something you are not?

I've had a 'discussion' about opioids with you before, wherein you insisted tolerance is due to increased numbers of receptors, a claim which is distilled horsecrap. All throughout that, and now too, you keep making ridiculous and outrageous statements concerning Biology and opioids.
I don't mind at all innocent mistakes or inaccuracies. It's when someone knows they have absolutely no basis to assert a claim, yet pretend they do. Worst example of this behaviour from him is here:
http://forum.opiophile.org/showthread.php?t=5451

(note: this refers to Hammilton only. Definitely not to Robojunkie or Jacky, for whom I have much respect)

Anyhow, I think further discussion on this specifically, if any, should be in a new thread. The on-topic message is that endogenous mammalian morphine does indeed have a solid basis and is part of the scientific consensus, and that opioid receptors are indeed widespread throughout the body, not only in the intestines and brain. Vascular tissue and WBCs come to mind.

And why not - an opportunity to link to a Kate Bush video:

"I want to be a lawyer
I want to be a scholar
But I really can't be bothered
Just gimme gimme gimme gimme gimme gimme gimme"


http://www.youtube.com/watch?v=xEVMfG8z490

[Raz]

^^^^ Oh dear...
Can some one explain where the endogenous opi is produced? I am a bit of a div where this is concerned..And what regulates, stimulates its production.For the opi receptor to be pumpin out its buzz,if naturally occurrin,what sends the" signal" there?Is it exercise, sex, or just stimuli?
Be cool and easy on the large scientific jargon, please.I'm still strugglin wiv Spanish...Raz

[Soda]

I'm going to preface this by saying I'm a knuckle head with no intention of offending you, but im definately not opiated at all times.....i WOULD KNOW

[Soda]

I love you jacky but this is the old "its only natural god wants us to to it" argument thats been used for shrooms and weed and everything......its not natural. its drugs. i THINK.

[stvip]

Can some one explain where the endogenous opi is produced?

I haven't checked, but one would assume the endomorphins (endorphins and enkephalins) are produced mostly in the brain. Morphine is synthesized in the brain (in several specific areas especially), by white blood cells, and possibly other types of tissue/cells.

And what regulates, stimulates its production.For the opi receptor to be pumpin out its buzz,if naturally occurrin,what sends the" signal" there?Is it exercise, sex, or just stimuli?

That's far too complex to answer, and is largely unknown anyhow.

As for the role of morphine specifically, that's even less understood. It's only in the few recent years that conclusive evidence has been gathered that mammalian endogenous morphine indeed exists (I say "mammalian", because it's been known for quite a while that morphine is not exclusive to Papaver sp. and plants; for example, helminths were known to synthesize and excrete it). The role it plays is still very much unknown (could have as much to do with immunology as with neuropsychiatry, and probably plays a link in the connection between the two - neuroimmunology). In fact, it is unknown whether it has any significant role at all, but having one is highly likely (because the synthesis pathway is quite complex and it seems unlikely something like that would've been evolutionarily conserved otherwise). There's very interesting research suggesting there's a mu opioid receptor splice variant which is specific for morphine. It's also worth noting that morphine has the peculiar property of causing desensitized receptors to remain on the cell surface, rather than being internalized, which has possible implications for applications targeting morphine tolerance and dependence. Examples for this is the article someone posted recently about abolishing tolerance through a single genetic change, the idea of doing the same through combining morphine doses with a methadone stereoisomer, or this research:
http://www.nature.com/npp/journal/v15/n1/abs/1380446a.html

I want a cookie.

[Soda]

*produces a cookie and pretends he understands the signifigance of science*

[jacky]

well its like this soda, our bodies produce morphine, and codeine, most likely in very small amounts, were not talking I think even in the milligram range.

but beyond that, our bodies use endorphins, natural hormones as chemical messengers. some of the endorphins are 1000 or more times more potent than morphine!
and many of the endorphins are actually avialable from peptide suppliers, scientific clearing houses for the chemical researchers.

if you didnt have some type of opioid/opiate peptide keeping your guts tone, then youd be passing your bowels out your ass.

look, its not some claim I am trying to make that we are loaded all the time, many of these compounds are most like rather subtle in their natural playground.

a few opiophiles have gotten certian peptides, and shot them up. one comes on hard and strong, but only lasts for minutes. that makes sense for a neuromessenger, quick acting, very potent, and doesnt last long. that way, more messages can get through the "line"...
dig?

really to clear this up, go to barns and nobles, or borders, or maybe your favorite well stocked book store, and get this book "zen and the brain" by James H Austin...you dont have to buy the book, or obviously a good college library, especially U of I in Moscow Idaho (where James H Austing taught/teaches)...
this book is written by a buddhist, zen meditation practitioner that just happens to be one of the neuro surgeons that started researching the opiate and dopamine pleasure pathways in the 70's-80's, I even think this guy was part of the group of researchers that first even found the opiate receptors.
it is very readable, and there is ALOT, of drug research in this book, both hallucingenic, dopaminergic and opioidergic speaking.
maybe some of the findings in this book are outdated now, but much of it is still relevant.
he talks about drug enforced neurogenesis...
he talks in depth about the cross stimulation, or paradoxical stimulation of dopamine by morphine/endorphins,
he makes a statement that opiates play a part in the zen/oceanic experience...

if I was arrested for opiate use, I would claim that it was an entheogenic experience (which it can be), and use this book as support that opiates are part of deep religious experience.

the book is written in a quick moving style, its readable, its both scientific text, and delves into the paranormal, or paradoxical mindstates.

simply one of the best books on drugs every written in my opinion.

read the book.
hell, do it on a sane dose of opiates if you want, it probably wont hurt your memory retention if you are at an optimum dose.

you might find out why some opiates actually increase dexterity, mathematical thought, and memory...see, the body uses natural opiates, endorphins to lay down, and retrieve memory, I am sure that there are other involved areas of the brain as well, but James H Austin has me convinced that the opiate receptors are at least a very important part of the process.
of course you memory goes to shit if you are nodding.
the optimum opiate dose is a fragile line...the amounts of morphine or endorphin used to be injected into specific sites in the brains of animals are very very small.
in one part of the brain, if you inject morphine, the ventral tegmental region of the mesolimbic system, you will get opiate activity, but when you cut off chronically administered morphine from this spot THERE IS NO WITHDRAWL SYMPTOMS....
put a chemical pump into my brain in this SPOT PLEASE.

in another area of the brain, on the top, in the middle, researchers took voluntary junkies, and performed office brain surgery basically. they used dry ice to create lesions, pea sized scars, on this part of the brain.
after this operation, many junkys had no withdrawl symptoms, and some were supported into sobriety, and then more amazingly, some people experienced opiate type euphoria, and some even felt HIGH for years after!!

put some lesions on MY BRAIN.!!!

just read the few chapters in this book for free, anyone who can read and understand english can make their way through these chapters and understand most of the language and concepts.

you will realize most likely, that endogenous opiates support many functions that we know about, and most likely I imagine, as more and more opiate sub type receptors, and interrelated pharmacological activitys in the body are discovered, that endogenous opiates play a larger role than every realized even a few years ago.

when I realized this I was overjoyed, mankind will not simply do away with opioid/opiate compounds, it plays to large a part in our pharmacology. I think in the future, if things go right, that opiate use will be more and more accepted as people become more knowleable.

when you learn that menthol has kappa opioid properties, that many herbs have mild type of opioid agonist effects, or indirect activity that effects the opiate receptors, that the mammilian body is simply peppered with opiate receptors all over the skin, in the brain, in muscles, and MOST of the bodys organs, that opioid and opiate activity is much more complex than anyone had in mind...
that the opium poppys and the mammilian bodys out there are factories of morphine production, using pretty much the same biosynthetic pathways as each other...
you might realize that opiates are pretty much a minute to minute consideration,
EVEN IF YOU ARE NOT TAKING EXOGENOUS, ORGANIC OR SYNTHETIC/PARTIAL SYNTHETIC OPIATE/OPIOID TYPE COMPOUNDS.

I know that I have said this before...
but burroughs even hinted at this possibility a long time ago, in my opinion.
when he wrote in Naked Lunch.........

"BUddha? A notorious metabolic junky.....MAKES HIS OWN YOUR DIG. In India, where they got no sense of time, The Man is often a month late....'Now let me see, is that the second or the third monsoon? I got like a meet in Ketchupore about more or less.'
"And all them junkys sitting around in the lotus posture spitting on the ground and waiting on the man.
" So Buddha says: 'I dont have to take this sound. I'LL BY GOD METABOLIZE MY OWN JUNK.'


a true fucking visionary.

anyway, that is what I understand...I am not an expert by any means, but its fairly obvious I believe, that opiate pharmacology is a deep subject, with the tip of the iceberg exposed to our present knowledge.

[Raz]

^^^^ I think nirvana= bein opi high.Or was budda just a junkie and that tree he sat under was where his connect lived?
Thank you Jacky for a well written piece.Even i understood it..Although science has always had the lowdown on what is "True", for as long as public perception remains; that drugs are evil, or at best wrong or illegal.We are not goin to see any advances in our personal freedoms, what we can put in our bodies.Or our freedom to choose.
What would be a fantastic discovery is; all the guys who use drugs and have endorphin deficiency have the same level of opi's as some of those bastards sittin in our gov!!...Whose fit for fuckin office now ya wankers...We could have the opi board runnin for office.On intelligence alone they would win hands fuckin down!!!

[Hammilton]

Why are you pretending to be something you are not?

I've had a 'discussion' about opioids with you before, wherein you insisted tolerance is due to increased numbers of receptors, a claim which is distilled horsecrap. All throughout that, and now too, you keep making ridiculous and outrageous statements concerning Biology and opioids.
I don't mind at all innocent mistakes or inaccuracies. It's when someone knows they have absolutely no basis to assert a claim, yet pretend they do. Worst example of this behaviour from him is here:
http://forum.opiophile.org/showthread.php?t=5451

(note: this refers to Hammilton only. Definitely not to Robojunkie or Jacky, for whom I have much respect)

Anyhow, I think further discussion on this specifically, if any, should be in a new thread. The on-topic message is that endogenous mammalian morphine does indeed have a solid basis and is part of the scientific consensus, and that opioid receptors are indeed widespread throughout the body, not only in the intestines and brain. Vascular tissue and WBCs come to mind.

Have you not bothered to read the book? There is indeed very good evidence of receptor proliferation. It's definitely not the only mechanism (ORL and Delta both play strong roles). If you can't provide a decent counter-defense just saying "it's horsecrap" isn't exactly very convincing. How about some sources or is that too difficult? As far as it is, you haven't showed anything, you've just whined about how wrong I apparently am (despite the fact that I actually have sources that confirm what I've said).

The theory that morphine is produced endogenously hasn't caught on for a reason: there's no evidence that it occurs under natural circumstances. Have you even read the study? Apparently not. It apparently happened in one study under very unnatural circumstances.

If you consider that conclusive evidence that it occurs in the human body under natural circumstances, you're not applying even the most basic level of critical thinking.

And (like usual) here's another source confirming the upregulation theory:
Peripheral opioid analgesic effects are augmented under conditions of tissue injury such as
inflammation, neuropathy, or bone damage (Kalso et al. 2002; Stein 1993; Stein et al. 2003).
One underlying mechanism is an increased number („upregulation“) of peripheral opioid
receptors. In dorsal root ganglia, the synthesis and expression of opioid receptors can be
increased by peripheral tissue inflammation (Zöllner et al. 2003; Pühler et al. 2004; 2006).
Subsequently, the axonal transport of opioid receptors is greatly enhanced (Hassan et al. 1993;)

I haven't read the Hassan paper, but I do have the Zoellner and Puehler papers in hard copy.

[edhorfin]

There's very, very little evidence that morphine is endogenously produced. The research hasn't been duplicated, and I don't think it's all that convincing until then. And even then it hasn't been shown to occur under natural conditions, in a few cell lines in petri dishes, heavily fed precursor amino acids.

It's quite possible that it is produced endogenously, but to date there just hasn't been a study to replicate it.

For one, there aren't opioid receptors all over the body, they're concentrated in two locations: the gut, the CNS. I'm certain there are some located in other locations, but they're decidedly few and far between.

There's no reason that any antagonist with a high enough affinity for the u-receptor wouldn't be able to block every receptor in the body. I mean "every" as in "almost every" since there's no way you could have one in the receptor every time, constantly. When they dissociate, there's bound to be a short time before another molecule comes and fills it again.

You're not going to experience what we're familiar with as opiate withdrawal from usage of these drugs, though. You're bound to experience some effects, but it's not the same.

The reason you can get high on naltrexone is because it's affinity isn't that high. Eventually you'll overpower it with the morphine. That's not true of antagonists with much higher affinity.


Hey Hamm!
Haven't seen you around in a while. Go to see you back. Interesting thread.

[SpecialGuy69]

THIS is everything an opiophile thread should be. Thanks, Jacky.

Glad to see everything is back to normal.

I'll comment on the actual content of the thread in a few years after I complete my molecular bio doctorate and catch up with you all.

[clinton]

im quite intRigued by all of this...
i had no idea hookwoRms cReated opiates that they excRete into theiR hosts...
it makes sense though...
good stuff,love the thRead......

[Soda]

well its like this soda, our bodies produce morphine, and codeine, most likely in very small amounts, were not talking I think even in the milligram range.

but beyond that, our bodies use endorphins, natural hormones as chemical messengers. some of the endorphins are 1000 or more times more potent than morphine!
and many of the endorphins are actually avialable from peptide suppliers, scientific clearing houses for the chemical researchers.

if you didnt have some type of opioid/opiate peptide keeping your guts tone, then youd be passing your bowels out your ass.

look, its not some claim I am trying to make that we are loaded all the time, many of these compounds are most like rather subtle in their natural playground.

a few opiophiles have gotten certian peptides, and shot them up. one comes on hard and strong, but only lasts for minutes. that makes sense for a neuromessenger, quick acting, very potent, and doesnt last long. that way, more messages can get through the "line"...
dig?

really to clear this up, go to barns and nobles, or borders, or maybe your favorite well stocked book store, and get this book "zen and the brain" by James H Austin...you dont have to buy the book, or obviously a good college library, especially U of I in Moscow Idaho (where James H Austing taught/teaches)...
this book is written by a buddhist, zen meditation practitioner that just happens to be one of the neuro surgeons that started researching the opiate and dopamine pleasure pathways in the 70's-80's, I even think this guy was part of the group of researchers that first even found the opiate receptors.
it is very readable, and there is ALOT, of drug research in this book, both hallucingenic, dopaminergic and opioidergic speaking.
maybe some of the findings in this book are outdated now, but much of it is still relevant.
he talks about drug enforced neurogenesis...
he talks in depth about the cross stimulation, or paradoxical stimulation of dopamine by morphine/endorphins,
he makes a statement that opiates play a part in the zen/oceanic experience...

if I was arrested for opiate use, I would claim that it was an entheogenic experience (which it can be), and use this book as support that opiates are part of deep religious experience.

the book is written in a quick moving style, its readable, its both scientific text, and delves into the paranormal, or paradoxical mindstates.

simply one of the best books on drugs every written in my opinion.

read the book.
hell, do it on a sane dose of opiates if you want, it probably wont hurt your memory retention if you are at an optimum dose.

you might find out why some opiates actually increase dexterity, mathematical thought, and memory...see, the body uses natural opiates, endorphins to lay down, and retrieve memory, I am sure that there are other involved areas of the brain as well, but James H Austin has me convinced that the opiate receptors are at least a very important part of the process.
of course you memory goes to shit if you are nodding.
the optimum opiate dose is a fragile line...the amounts of morphine or endorphin used to be injected into specific sites in the brains of animals are very very small.
in one part of the brain, if you inject morphine, the ventral tegmental region of the mesolimbic system, you will get opiate activity, but when you cut off chronically administered morphine from this spot THERE IS NO WITHDRAWL SYMPTOMS....
put a chemical pump into my brain in this SPOT PLEASE.

in another area of the brain, on the top, in the middle, researchers took voluntary junkies, and performed office brain surgery basically. they used dry ice to create lesions, pea sized scars, on this part of the brain.
after this operation, many junkys had no withdrawl symptoms, and some were supported into sobriety, and then more amazingly, some people experienced opiate type euphoria, and some even felt HIGH for years after!!

put some lesions on MY BRAIN.!!!

just read the few chapters in this book for free, anyone who can read and understand english can make their way through these chapters and understand most of the language and concepts.

you will realize most likely, that endogenous opiates support many functions that we know about, and most likely I imagine, as more and more opiate sub type receptors, and interrelated pharmacological activitys in the body are discovered, that endogenous opiates play a larger role than every realized even a few years ago.

when I realized this I was overjoyed, mankind will not simply do away with opioid/opiate compounds, it plays to large a part in our pharmacology. I think in the future, if things go right, that opiate use will be more and more accepted as people become more knowleable.

when you learn that menthol has kappa opioid properties, that many herbs have mild type of opioid agonist effects, or indirect activity that effects the opiate receptors, that the mammilian body is simply peppered with opiate receptors all over the skin, in the brain, in muscles, and MOST of the bodys organs, that opioid and opiate activity is much more complex than anyone had in mind...
that the opium poppys and the mammilian bodys out there are factories of morphine production, using pretty much the same biosynthetic pathways as each other...
you might realize that opiates are pretty much a minute to minute consideration,
EVEN IF YOU ARE NOT TAKING EXOGENOUS, ORGANIC OR SYNTHETIC/PARTIAL SYNTHETIC OPIATE/OPIOID TYPE COMPOUNDS.

I know that I have said this before...
but burroughs even hinted at this possibility a long time ago, in my opinion.
when he wrote in Naked Lunch.........

"BUddha? A notorious metabolic junky.....MAKES HIS OWN YOUR DIG. In India, where they got no sense of time, The Man is often a month late....'Now let me see, is that the second or the third monsoon? I got like a meet in Ketchupore about more or less.'
"And all them junkys sitting around in the lotus posture spitting on the ground and waiting on the man.
" So Buddha says: 'I dont have to take this sound. I'LL BY GOD METABOLIZE MY OWN JUNK.'


a true fucking visionary.

anyway, that is what I understand...I am not an expert by any means, but its fairly obvious I believe, that opiate pharmacology is a deep subject, with the tip of the iceberg exposed to our present knowledge.

I feel you man. Sorry to get you riled, but you said some pretty deep shit just now.

[stvip]

I haven't replied with citations previously because I was hoping your complete, utter lack of understanding would be obvious to all. For example, the chart you provided showing the exact opposite of your claim. Or more generally: you claim receptor density quantification is impossible (nonsense), yet provide a chart (which you misunderstand) relying upon that exactly, only using arbitrary units of measurement for the sake of comparison, which you stated were used because quantification is impossible (which makes absolutely no sense, on the basic logical level). And it only gets worse from there, yet all the while you confidently use language meaning to suggest you're knowledgeable, and belong to the field as a fellow scientist (as in: "The increasing number of opiate receptors has been so thoroughly studied we've actually gotten the ability to chart the relationship of receptors, occupancy and the resultant LD50.", which by the way, also confuses ED50 with LD50).

You still need a reference? I'm going to make it easy for you and provide them in the form of links:

http://jpet.aspetjournals.org/cgi/content/abstract/256/2/575
http://jpet.aspetjournals.org/cgi/content/abstract/306/1/179
http://www.ingentaconnect.com/content/els/00913057/2001/00000069/00000001/art00525

Now, it's cute that you refer me, an actual working academic researcher, to a book written two decades ago. That's ancient history. Back then, there were indeed good reasons to be skeptical about the endogenous mammalian morphine hypothesis, but of course, you pass it off as your own skeptical, rational observations after carefully pouring over the published data, as your fraudulent habit has become. However, for a few years now, it's been conclusively proven, and is part of scientific consensus. For example, when a paper is published in Nature (the implications of which I hope are clear), the existence of EM is a given (say, here: http://www.nature.com/npp/journal/v15/n1/abs/1380446a.html).

To elucidate - it's not about Hammilton being wrong over a technical, academic issue. It's not a gentlemen's disagreement. It's about being deceitful, passing himself as something he isn't. I keep seeing this kind of behaviour in online forums - people posing as someone else, divulging disinformation. When it comes to scientific or technical issues, most people don't have the ability to discern the truth from ridiculous, silly claims, and sooner or later, some dangerous falsity is passed on.

[stvip]

Oh, and about the other studies you've referenced: Tissue inflammation may indeed promote opioid receptor upregulation. That's simply irrelevant to your claims.

[Soda]

I love it when it heats up like this.:D

[jacky]

ohh Soda, you didnt rile me...

I wouldnt have believed any of this myself 20 years ago.

and its also not like these endogenous opiates make you feel loaded while they work.

I remember a quote from a doctor, concerning people that are "addicted" to working out. some of these exercise/running, endorphin freaks actually kill themselves doing so.
I knew a young triathelete who did this very thing.
he died exercising, and he had a hear condition to boot.
anyway, the doctor said that people who get used to this daily endorphin rush, get hooked, physically to the practise.
if they dont get the exercise they cannot sleep, feel crappy etc.
the doctor surmised the daily output of endorphins that these people become reliant upon to being equivalent to a 50 milligram of morphine a day dose.

there are plenty of opioid active compounds out there, but very very few that are like morphine.

if someone could take the kappa opioid agonist menthol compound, and turn it into a mu agonist compound, then we would have a precursor material that costs about 20$ for a pound of the pure powder.

there are all sorts of possibilitys.

but still, even with all these natural opioids working in the body, the endorphins, etc, we are still in pain and needy creatures of habit.

my point of all this is that morphine and other opioids exist naturally in the body, we depend on the opioid systems for more than pain relief.

and this is just the beginning of the show, the curtains have just gone up on this one. the science of opioidergic activity in the mammilian model is young.

[strikks]

sure, they function on naltrexone, but that doesnt mean that the bodys endorphin function is shut down all over the body, there are opiate receptors all over the human/animal body...

and naltrexone doesnt block opiates all the time anyway, I used dope on naltrexone, and felt it after a few hours just fine, it only took 2-3 times my normal amount, a 40$ piece got me high no problem.

all I am saying really is that opioid/opiate endorphins play a large part of our minute to minute consiousness, they play hormonal roles, not just pain perception augmentation.
if all the bodys opiate receptors shut down, you would not be in a state of mind and body to do anything but suffer...you would not be able to recall, memorize, or basically walk without major disfunction.

experience forced withdrawl and then tell me about it, ha ha. you wouldnt last long in that state, even under medical supervision.
and that is only shutting down the receptors in the brain for the most part...and bowel tract.
SHUDDER.

your right,everybody that abuses opiates feels incredibly hypersensitive to pain because of this. also,we deplete our systems of this "natural" opiate in our bodies which makes up part of w/d and depletes the dopamine also so you never feel good normally until you get that dope in there.

i ain't up on the scientific shit ,but from my experience it makes sense and the body never produces enough to get high or even take all the pain away,but if you were"clean"normal person and break your leg, it would hurt worse without that/those systems/receptors also i think when people go into shock from pain that those "systems"/or whatever help put you unconscience/asleep for protection or what ever.


.......whatever....good thread!!

[Soda]

You have to take into account all the crazy things people are capable of doing when "withdrawing". I wont even use me as an example even though I'm my favorite person. Think of Courtney Love who acted her ass off in that movie about Hustler, acting that she was stoned after shaking like a leaf in the bathroom. I mean, not only that, but like, where there's a will there's a way, and withdrawing addicts are only sometimes reserved to ride it out in their beds. I've seen addicts who are much more....proactive about waiting out the sickness....you know.

[starglazer33]

Jacky, thank you, thank u, thank you!!

This I believe and this i could not ever put into words. This is what opiophile is all about! 100%

Truth is meditation can and will be effective in as many ways as there are people who meditate and as far as the brain and body becoming fluid in certain chemical both naturally and unaturally is just cellular evolution and spiritual adaptability to the all. I ain't so smart but I believe that 'spirit itself is chemical' least thats what a bunch of lab rat brilliant phd overdosees say. I read it in Tim Leary's something or other about cryogenics and the brain the book may have been A Design for Dying or Robert Anton Wilson's The Cosmic Trigger the final secret to the illuminati vol 1,2,n3. can remember which. Anyway i have read at some point that something or other about our genetic templates are a kind of language and that in the mind it may be necessary to 'up'the levels of drugs in our bodies in order to understand certain criteria of a higher nature,or a language so to speak.

I am not so smart as i have said but you guys are a teaching me stuff and i just wanna say thank you sooo much. Makes me feel hope for the future and less alone! Most dopefiends tend to have less of a tolerance for such subjects and leaves me feeling as though "damn what if the vox populi,or the moral majority are right " naaahh never, even if they are then fuck em, good thing i worship the devil and dope is my hero. Just kidding I just can't see drugs as a big bad devil thing that should be feared and demonized in order to save our children and ourselves and that we should stay as far away from them as possible. I really enjoy hearing some sord of objectified tolerant type understanding about natural compounds that can be used for both recreation and spiritual and mental developement.

I really loved the book Diary of a Drug fiend by Aleister Crowley read it when i was 16 and read it around 5 times since so long as i can remember the book never gets old it always fascinates me as the more i learn the more i can go back and get something out of it that i had not gotten previously. you and robojunkie really impress me greatly. I truly wish i had half the science in my mouth that you guys have so i can correspond some of these high ideas in my burned out but stillgrowing brain. In majick all things are possible.

Sex,Magick and drugs, a book by Robert Anton Wilson,Henry Miller and Isreal Regardie which I have yet to read but i believe touches on some of this plus orgasm and the brain is my next purchase.(its been a long long time since ive seen the book and might have one or two Authors mixed up its written by three docs thouhg im sure of the first 2) After that imma gonna buy dat udder book you mention it sounds good if I can get my dumbass brain around it.

You guys are great, thanks once again Jacky on an excellent thread!!! :D

P.S. I know im a nut and sorry if i wasted anyones time please bear with me i am my own inner-child.
May your h.g.a/d.n.a guide you all in the direction of light and will of your own choosing and godsblessya in the meantime!!! ...............sg33

[Soda]

See, this is what opiates are for. You can't write posts like those above without em. See how he/she loves everyone? It'll be gone in a few hours.

[starglazer33]

wtf im on methadone and have acute depression!! heroin is the only thing that gets me high!!or alcohol and benzo=methadone, when i post then no one not even me understands it!:o The only thing that makes me love everyone besides lsd is the fact that there is so much suffering in the world whenever i see any amount of positive influence and people sticking together always makes me feel hopeful. I could go on forever but believe me if i were wanting to spread all negativity around everypost would be pages of all shyte. I AM AN UNSLAVAGEABLE PESSIMIST!!! and a pagan, nature is a god from which man is a byproduct.

i JUST don't wanna share it all all the time, what good would it do!?! I love intel because in the end all we are are info bytes! Plus mean people are stupid a common shared trait among abusers of humanity. So people who are really really intelligent inspire me thats all!Plus i love the openmindedness though i hate those who are so open minded thier brains fell out!

I know im wierd "love is the law."

........................sg33 end transmission.
I guess im just a dork or something im getting older done time and tired of being tough even tough guys especially tough guys understand the need for a peaceful mentality and understanding. Keeps me sane!or close to it anyway!

[Soda]

Is the methadone helping the depression at all?

[starglazer33]

Yes and no. It numbs me out for the first two hours or so but then the fact that Im on it and see no way out just adds to it. Plus the way those counselors/workers treat me and some others leaves me feeling no better than cattle and the issue with the other clinic and the phone message broke my heart and my spirit as it is so far removed from who I really am.Since then I feel hopelessly horrible about myself.I know its not that big a deal for most but for me I'm crushed, I will never be the same.It overwhelmed me inside cuz nothing like that has ever happened to me before in my whole life. Dem clinics make me feel like who I am is wrong and a bad person.Like I said in said message "I am your abbo,your lacky,Your blank" I feel like thier slave with no hope of living up to thier standards.

Its a small wonder how I have never noticed it was that bad I mean I knew there was a stigma surrounding heroin use but here where I live people look to you as if you are diseased with a highly contagious evil incarnated or something wicked to the core.

Overall the whole scenario bleeds me dry mentally, physically, and spiritually. I don't know why but ever since I decided to quit running dope all my efforts at getting my life back together seem to fail.
It just seems everything gotten worse since I quit getting high and now without recourse of one good shot every now and then.(I know better and tried it and it really doesn't do it for me like it use to) God I miss it! Not a day goes by I don't think about it.

Whoa, sorry Im ranting I guess my answer is an overall grey haze on an autumn sky.
I honestly cannot recall the*feeling* of happiness outside of a few fading moments. Around ten yrs ago or so I remember being happy living not merely surviving seems like it was someone else life now though.

Peace...everybody.................sg33

[Soda]

Yes and no. It numbs me out for the first two hours or so but then the fact that Im on it and see no way out just adds to it.
At least it isn't exactly unhealthy for your body, and you may wake up one day with a desire to use less.

Plus the way those counselors/workers treat me and some others leaves me feeling no better than cattle and the issue with the other clinic and the phone message broke my heart and my spirit as it is so far removed from who I really am.
What was the phone message?

Since then I feel hopelessly horrible about myself.I know its not that big a deal for most but for me I'm crushed, I will never be the same.It overwhelmed me inside cuz nothing like that has ever happened to me before in my whole life. Dem clinics make me feel like who I am is wrong and a bad person.Like I said in said message "I am your abbo,your lacky,Your blank" I feel like thier slave with no hope of living up to thier standards.
Having no personal experience with clinics I can say I'm shocked that they really treat you that poorly. It is a disgrace that abusive people are allowed to hold such a sensitive role in your life, and they should not be hired unless they are understanding of opiates and the whole complex wisdom that follows.


Its a small wonder how I have never noticed it was that bad I mean I knew there was a stigma surrounding heroin use but here where I live people look to you as if you are diseased with a highly contagious evil incarnated or something wicked to the core.

Overall the whole scenario bleeds me dry mentally, physically, and spiritually. I don't know why but ever since I decided to quit running dope all my efforts at getting my life back together seem to fail.
It just seems everything gotten worse since I quit getting high and now without recourse of one good shot every now and then.(I know better and tried it and it really doesn't do it for me like it use to) God I miss it! Not a day goes by I don't think about it.

From experience, both personal and observed, it sounds like you are a relapse waiting to happen. Just BE CAREFUL. That's what I was told, so the "be careful" line, as useless as it may be, is the only way I have of fooling myself into thinking I'm helping anyone. ;)



Whoa, sorry Im ranting I guess my answer is an overall grey haze on an autumn sky.
I honestly cannot recall the*feeling* of happiness outside of a few fading moments. Around ten yrs ago or so I remember being happy living not merely surviving seems like it was someone else life now though.

You aren't ranting, I wish more people were as open as you. There is one constant with depression, unless you kill yourself IT ALWAYS LIFTS EVENTUALLY, WITH OR WITHOUT MEDICATION.

[starglazer33]

I dont necessarily understand either but from the last clinic I was at I was only one of about 15 people i know that are now at the clinic I am at. From what the newest person told me was that general rule if you did everything they asked of you they tossed you out. None of the counselors that had any kind of pull, really cared for helping addicts in my opinion. I was going to other counselors there and talking with them about my problems instead of my assigned counselor. My original counselor quit she had been there from the beginning and she gave me a hug and said her words

"I am sorry, I can no longer work under these 'new' conditions. I will not treat you guys*patients* the way the want me to. Things are changing here and it is no longer about helping people it is only about the money and people getting experience so they can counsel/advise 'real' people who actually want therapy not 'junkies'. These new younger counselors are tricky and only want a leg up.Thier ambition outweigh their intentions toward the patients,they are using new 'tactics' just to see a desired effect. And I want no part in it. I am so sorry I am not bailing on you I just can't..."

Then she started to cry and I sord of got vaklempt myself gave her a hug and it was all downhill from there. My mouth dropped at how open and straightup she was with me but then at the same time I shared everything with her and she knew it.We got pretty close in 9 short months she helped me out. A few short months later and every counselor I had come to trust quit,and I was reffered-kicked out for being an overall trouble maker.There's more to it but I no longer want to discuss it as it is a sensitive subject which can easily be misconstrued.(I asked all the right questions in a group and was relatively relentless about fairness and in the end probably deserved earned it.)

It was my overall first clinic experiecne and I was astonished at the treatment that went on yet I realize that some of the patients are extremely difficult to deal with and it wasn't all the counselors at first. Now i'm at a new clinic and still see more people transferring over everyday. A friend of mine who has been a patient thier for 7 yrs just transferred, they are trying to pass a law/rule there that you have to have someone designated drive you there,wtf!

This new clinic is really no different in the attitude from the people who work there but at least it is upfront and now I know better. Still though I wish I could talk to someone I trust and speak my mind freely but I just keep my head down and keep to myself cuz of what I've read here about snitches and stuff this is a common problem from clinics all around from what I gather.

Anyway, Iv'e said too much and althoough this thread was probably finished with the moment I opened my big fat arrogant,inept mouth people probably abandoned it. I am sorry for 9highjacking or whatever.
this was an incredible thread and i had no bisuness or good sense to just leave it alone but i couldn't help myself i knoe i ain't all that smart but i still love reading and intel stimulation and the subject even though I knew my wits are incompetent in comparison with these really great and insightful opphiles'I am at the very least proud to be a part of something even if in minute,useless ways,Im trying and one day I hope to get better at this. I am computer new this is the only web-site i ever visit anymore I am addicted to it,proud of what i read here and that there are people that exist like these here is amazing to me, just dumb-luck i found it. Sorry again Jacky gotta go sg33

[xxanxx]

If Morphine was produced Endogenously why would we not develop a tolerance to the natural morphine but when we take morphine Exog-....the outside pill shaped kind we do? If it were produced naturally, and lets say any and all opiates that we find in nature didn't exist, wouldn't this mean that throughout a person's lifetime we would progressivley feel less and less joy. That is unless the body automatically upped the dose.




Is this something he talks about a lot in the book? I remember you recommending this book to me a long time ago but it must have slipped my mind. I think I will have to get it this time though I've never in my life ever even attempted to meditate and that is something I have been thinking about remedying.


My only question, which I imagine there is no answer to, is why is it so necessary for the body to experience pain? I realize it's a defense mechanism so people kill themselves by standing in a fire or jumping into oncoming traffic but one thing I never understood was, for instance, say I slam my toe into a wall. Why does that sensation of pain have to linger for such a long period of time. Afterall I realize what I did and I know not to do it again. Or say I break my leg. Why is the pain a person experiences in the following weeks necessary. Does the brain not recognize the fact that the leg is now in a brace or cast and is being taken care of. I mean....I know my leg is broke. I know I need to take it easy on the leg. So why do I need the constant reminder?

It may be a stupid slightly off topic question but I wonder if anyone can enlighten me in anyway.


Great stuff as always Jacky. Your the man (even though I thought you were a women for a few months back when I first joind O-phile).

Interesting stuff as always. I can't wait to read more of James H Austins' work.

Evolution, my friend.

[Hammilton]

I haven't replied with citations previously because I was hoping your complete, utter lack of understanding would be obvious to all. For example, the chart you provided showing the exact opposite of your claim. Or more generally: you claim receptor density quantification is impossible (nonsense), yet provide a chart (which you misunderstand) relying upon that exactly, only using arbitrary units of measurement for the sake of comparison, which you stated were used because quantification is impossible (which makes absolutely no sense, on the basic logical level). And it only gets worse from there, yet all the while you confidently use language meaning to suggest you're knowledgeable, and belong to the field as a fellow scientist (as in: "The increasing number of opiate receptors has been so thoroughly studied we've actually gotten the ability to chart the relationship of receptors, occupancy and the resultant LD50.", which by the way, also confuses ED50 with LD50).

You still need a reference? I'm going to make it easy for you and provide them in the form of links:

http://jpet.aspetjournals.org/cgi/content/abstract/256/2/575
http://jpet.aspetjournals.org/cgi/content/abstract/306/1/179
http://www.ingentaconnect.com/content/els/00913057/2001/00000069/00000001/art00525

Now, it's cute that you refer me, an actual working academic researcher, to a book written two decades ago. That's ancient history. Back then, there were indeed good reasons to be skeptical about the endogenous mammalian morphine hypothesis, but of course, you pass it off as your own skeptical, rational observations after carefully pouring over the published data, as your fraudulent habit has become. However, for a few years now, it's been conclusively proven, and is part of scientific consensus. For example, when a paper is published in Nature (the implications of which I hope are clear), the existence of EM is a given (say, here: http://www.nature.com/npp/journal/v15/n1/abs/1380446a.html).

To elucidate - it's not about Hammilton being wrong over a technical, academic issue. It's not a gentlemen's disagreement. It's about being deceitful, passing himself as something he isn't. I keep seeing this kind of behaviour in online forums - people posing as someone else, divulging disinformation. When it comes to scientific or technical issues, most people don't have the ability to discern the truth from ridiculous, silly claims, and sooner or later, some dangerous falsity is passed on.

Did you actually read those papers? First one says I'm wrong, second one does't provide much (though I haven't read it in it's entirety yet) and the final one says I'm right.

Until I get through the second paper, we're still 50/50. Why you used a paper that said I was right to say I was wrong, I dunno.

I have seen a more recent paper that actually parsed the route in which the human body can produce morphine. So, it can happen.

The question is whether or not it actually does happen in natural conditions though.

[jacky]

I might be unscientific as hell at times, but there is something to say about a person that is at least willing to try and perceive what a substance will do in their own body..

I took information about endogenous morphine found in animals as further support that morphine is produced in mammals and other animals as well as humans....though, as someone points out, the occurence in humans could just as well be a labratory created anomaly...
the substance has shown up in toad skins, mammal tissues, and milk I believe.

thanks for pointing that out,
I should also let people know from time to time, not to be an asshole or anything, that I have no college degrees, dont perform scientific work besides botanical and organic chemical studies, and only then as an amauteur.
I have a high school equivalency....and up until 8 years ago, I was a sloppy drug user and spent a few years living from space to space, on the street a little, etc etc.
I have a penchant for data.
I know that a good percentage is outdated, or plain wrong.
opioid/opiate activity isnt even fully understood in the case of other receptor types and endocrinological interactions upon the "opiate effect" are concerned

still,it is interesting to find herbs that have no reported opioid/opiate type compounds seemingly having supportive effect on withdrawl or tolerance.

my main interest is how this can all trickle down to the common opiate user, be they junky, pain patient, or both.
its a slow trickle.
95% of the "candidates" I loose interest in, either opioid active compounds are not really felt, or they cause dysphoria
some data can be misleading, especially to a "householder" initiate.

what I am interested in, mainly, is the slow though sometime rewarding process of networking with people online, to source rare plant materials that have opioid effects.
most I have researched were sitting under our noses the whole time in the dietary supplement industry.

example:
I have attained enough leaf material of a specific tree species in australia that produces grandisine type compounds.
particularly the most potent analgesic, delta opioid agonist I believe is grandisine f.
hopefully a chemist freind will isolate the interesting compounds of interest.
and someday I might cautiously proceed with investigations.
I look at it as simply as a natural right to consider new food/medicinal herb sources, and focusing interest on particular organic components.

the specifics are always interesting, and it is nice to know, but its also nice to not know, and to try and find out.

before salvia divinorum was "found out" that is...before scientists had found that salvinorin a was a kappa opioid agonist, I considered that very possibility, from the effects of the plant alone...after only a few experiences.
I am not claiming anything substantial here, other than a person doing bioassay may not always be the most informed (lets hope they try to be) but they are involved INTIMATELY in this process of research, and even drug creation.

the active opioids in dalea purpurea might look good on paper, but my intimate experience with them leaves me happy to conserve the sample isolates I have from that plant for reference compound research.

[Hammilton]

pawhuskin A is pretty potent. I can't find it's structure though. I'm guessing that if it's not working well, it's probably readily destroyed.

Have you seen the 'stacked indoles' from psychotria colorata? They're NMDA antagonists (and quite potent IIRC), psychotridine is the most potent I think. Very, very interesting.

I believe a vendor should be offering quality extracts (30%+) of it soon; not positive, but I know he's got an extract made.


My #1 right now would be the mitirone-type's found in Salvia nemorosa. I know at e-dot they're practically praying that they're opioids (and in one study, naloxone blocked the analgesic effects, but it would (at least partially) for ethanol too), but looking at what has been found in it, it's mostly likely a GABAergic. Then again, weirder things have happened.

[jacky]

the pawhuskins felt pretty shitty.
I took a isolation of the actives of dalea purpurea, prepared by a lab chemist. now, I am completely relying that this person knew what he was doing. so far, he has done pretty well with isolation of various other little known compounds...so I am not completely sure he had all the right stuff collected, but that was what he claimed.
for 20 minutes I felt a bit warm after taking almost a gram of the isolates. I had tried smaller amounts before, and noticed little.
at the 30 minute mark, I felt what could be a wave of warmth and euphoria, and then quickly, minutes later, I felt real sleepy, and yawning, and my eyes were watering.
I felt like crap for 3 hours. like I took some cold medicine/antihistamine. yawning, lethargy, running eyes....felt like kicking to a degree.

after I felt a bit better, I took some standard opiates, and decided that Dalea P. does not seem to have much potential at least as an herbal product.

I have heard of the various opioid active or nmda active psychotria species.
even had a contact in Brazil in the plant business put the word out to his various resources for plant materials that a supply line of any one of the purported active species might garner a decent profit in the future.
He also lived near an area where p. colorata was known to be collected. but things change, and 50 years is a long time for different plants to take over, or for farming practices to destroy everything natural in the area.

when a new species like this is first sold, I personally dont want access to just the extracts or isolates. I want the material in a form that might be somewhat researchable, leaf form, etc. to have a chance in hell of proper identification.
unless reference compounds exist.

what used to be a pretty well run, natural products business, can be turned into some secret proprietary knowledge bullshit clearing house, you know what I mean?
when people get their hands on a novel/rare product, and act like they "discovered" something, or that they alone should have the right to knowledge that otherwise a few years before was shared for the common good, I am not interested.

hopefully some info is shared if any interesting psychotria species are brought to the market.
where the plant was harvested, etc, is always nice to know for personal records.

I am still waiting for some more data regarding salvia nemorosa to come up.
the Iranian researcher working with this plant wont return my emails, though I am not suprised.
all my bioassays of various nemorosa variants have been mundane at best.
and alot of the people buzzing about its amazing activity, are either using opiates/opioids or stimulants on a daily basis, so perhaps there is more potentiation happening than anything?
I havnt heard of one pain sufferer taking the herb and getting anything.

I am going to try and talk a company that grows salvia nemorosa outdoors near my home into letting me get some tops of the plants harvested this fall.
they grow their plants all year for greater durability, and in the fall they cut them back, and throw all that material away...could be a nice haul that could produce some biomass for future extraction.
the only chemist I know working on the plant in the USA told me that the roots seemed to hold the most promise.

unfortunately for me, a research partner with chemistry skills is now lacking. my prior supplier of interesting extracts/isolates is now so busy and out of the country much of the time.

I have been interested in getting some of the eleaocarpus grandis leaf material I am getting from Australia researched further.
the alkaloids of interest are of the grandisine type.
grandisine F, is supposed to be the most active,
the whole range of grandisine compounds seem to have some activity, mostly delta opioid agonists...but I think I remember some possible kappa or sigma activity as well.

youve got my interest piqued hammilton, let me know if any psychotria products do become avialable, besides of course psychotria viridis.

[Mayo]

...
I took a isolation of the actives of dalea purpurea, prepared by a lab chemist. now, I am completely relying that this person knew what he was doing. so far, he has done pretty well with isolation of various other little known compounds...so I am not completely sure he had all the right stuff collected, but that was what he claimed.....

Hi jacky. I'm sure you know a lot, I'll just ask this: Was a chromatogram provided to you along with the isolated compound(s)?

Chemists in to extractions take a lot of pride in their work :), but purity is ALWAYS confirmed with instrumentation,
so a record (some form of chromatogram or spectrum) must exist.

Thanks for the 'phile!

[stvip]

Did you actually read those papers? First one says I'm wrong, second one does't provide much (though I haven't read it in it's entirety yet) and the final one says I'm right.

Until I get through the second paper, we're still 50/50. Why you used a paper that said I was right to say I was wrong, I dunno.

I have seen a more recent paper that actually parsed the route in which the human body can produce morphine. So, it can happen.

The question is whether or not it actually does happen in natural conditions though.

This isn't even a question of science anymore - you seem to lack the most basic English comprehension abilities believing the third paper supports your claim ("parse" it with a dictionary, perhaps).

[jacky]

no, there was no additional data provided to me with the purported isolate materials...

but this person is fairly trustworthy chemist, and has isolated plenty of compounds for sale for the fine chemical market.

he works with chromo- equipment, basic equipment I guess, nothing too new or fancy, but good enough to produce a variety of isolated kratom compounds and such.

the work is and always has been done for free, in the spirit of providing a layman with some material for research.

he has made some errors in the past, and in those few incidences, updated his data to inform people who follow his work.

really, I dont know alot, ha ha.
I am a definite layman in all of my areas of interest, though I would consider myself a seasoned opiate/opioid user, and fairly knowledgeable in the realm of plant medicines, I am definitely sketchy at times with my pharmacology knowledge and such.

I put my opinions out there though, because its the only way to peer into deeper areas, sometimes someone who seems to know more updates me, or lets me know that I am dead wrong, or probably wrong.
alot of the reason I started this website is because I want to know more about opiate issues.

strangely, and I dont know how, shortly after I started this website, a few times, I recieved periodical published magazines of the opiate/opioid pharmagological research community.
with no mail fees or stamps on the envelopes. so someone in this small city knows something about me, and just happens to have these pain managment/opiate research magazines on hand?
very very strange.

the anecdotal evidence is looked at by many as having little use.
for my purposes though, it does have use, its one of the few tools to carry into the realm of the layman practice of researching rare plant materials when consuming them internally.
you shooting into the dark, with mostly blanks, and risking your health.

without sharing experiences, we are wasting the energy of research.

anecdotal "evidence" might be the only hint that something is of interest, besides the scientific abstract, and both can be shoddy leads.

what is great, is when people with deeper knowledge get on here and argue facts and such....some light is caste from time to time, but mostly it seems feelings get hurt, and people get pissed.

most of the chemists and chemistry students that I approach with offers of sharing research,or paying to do isolations are not interested in devoting much time to this type of research, even if they have interest in organic psychoactives.
I rely on a few people that occasionally are interested in the same plants.

so far, chaste tree isolates have been the most interesting.

alot of the interest back in the days of the HIVE was with synthetics, but a few people relished the natural worlds offerings as well.
what we need here, is more chemists involved in discussion, the problem is mostly ego I find.

I worked recently with a chemist that used to design drugs, he quit astra zenica cause of the chemists overblown ego's...what I found was, even though he was a nice guy, is that he let his own knowledge blow his ego up a bit too much, his interest in psychoactives was pretty much purely to make money, at the end of a shift, he was more interested in getting wasted and chasing girls.

it takes a lot of chemists to find just one that has an interest similiar to ours.

with the material I recieved from dalea purpurea, it was described as a blend of pawhuskin and related compounds.
there is a nice report on the plant, done by scientists interested in its opiate activity, and I assume that is the report he used when going to research this plant himself.
they guy has talents, but of course I take into account that there might be some mistakes made along the way.
I wouldnt suggest to anybody that they do the same thing I am, but if they do, I want to hear about it!

without anecdotal evidence I might have kept up my research into the voacanga plant, after a bad experience with the seed material, I was still interested in the root bark isolates.
until I read recently that someone else had a bad experience with that material as well.
I will still be interested in other peoples experiences with the consumption of this plant, but unless there is some glowing new reports, I am done with that one.

I recently learned of the legendary character known as Shen nong, an early researcher of medicinal plants who tasted his way to creating the pharmacopeia of traditional chinese herbal medicine.
this strange "horned headed" and leaf clothed chinese man tested different plants and eventually gave his life to this act of gaining knowledge...where myth and fact end and start concerning the strange horns on his head I dont know, but the mythical nature of the story and his sacrifice is certainly stimulating!

[Hammilton]

This isn't even a question of science anymore - you seem to lack the most basic English comprehension abilities believing the third paper supports your claim ("parse" it with a dictionary, perhaps).


Did you actually read the paper? I mean, did you even read the title?? It was "u-Opioid Receptor Downregulation Contributes to Morphine Tolerance." Here's the abstract:


Document Title:
μ-opioid receptor downregulation contributes to opioid tolerance in vivo

Authors:
STAFFORD Kristi (1) ; GOMES A. Benedict (1) ; JI SHEN (1) ; YOBURN Byron C. (1) ;

Author Affiliations:

(1) Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions. St. John's University, 8000 Utopia Parkway, Queens, NY 11439, ETATS-UNIS

Abstract:

The present study examined the contribution of downregulation of μ-opioid receptors to opioid tolerance in an intact animal model. Mice were implanted subcutaneously with osmotic minipumps that infused etorphine (50-250 μg/kg/day) for 7 days. Other mice were implanted subcutaneously with a morphine pellet (25 mg) or a morphine pellet plus an osmotic minipump that infused morphine (5-40 mg/kg/day) for 7 days. Controls were implanted with an inert placebo pellet. At the end of treatment, pumps and pellets were removed, and saturation binding studies were conducted in whole brain ([3H]DAMGO) or morphine and etorphine analgesic ED50s were determined (tail-flick). Morphine tolerance increased linearly with the infusion dose of morphine (ED50 shift at highest infusion dose, 4.76). No significant downregulation of μ-receptors in whole brain was observed at the highest morphine treatment dose. Etorphine produced dose-dependent downregulation of μ-opioid receptor density and tolerance (ED50shift at highest infusion dose, 6.97). Downregulation of μ-receptors only occurred at the higher etorphine infusion doses ( > 150 μg/kg/day). Unlike morphine tolerance, the magnitude of etorphine tolerance was a nonlinear function of the dose and increased markedly at infusion doses that produced downregulation. These results suggest that μ-opioid receptor downregulation contributes to opioid tolerance in vivo. Therefore, opioid tolerance appears to rely upon both receptor densitydependent and receptor density-independent mechanisms.


(italics and bold added for emphasis and ease of reading).

It's no surprise that after seven days significant downregulation wasn't occuring for something like morphine. It's well known that the super potent opioids induce receptor internalization (ie: downregulation) rapidly, and that tolerance develops much faster with them than other opiates.

some more:


Mu-opioid receptor regulation during opioid tolerance and supersensitivity in rat central nervous system


A Diaz, F Ruiz, J Florez, MA Hurle and A Pazos
Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, Santander, Spain.
We have analyzed by radiometric procedures in rat central nervous system the changes in the properties of mu-opioid receptors associated with tolerance and supersensitivity to the opioid agonist sufentanil. This study has used [3H]-[D-Ala2,MePhe4,Gly- (ol)5(2)]-enkephalin, a highly selective ligand, to label mu-opioid receptors in both membranes and tissue sections. The induction of opioid tolerance by chronic infusion for 7 days of high doses of sufentanil, a high efficacy agonist, produced mu-opioid receptor down-regulation, with a significant decrease in their density in both cortical (-67%) and spinal cord membranes (-55%) and no changes in the affinity constant. Autoradiographic studies showed an overall decrease of[3H]- Ala2,MePhe4,Gly-(ol)5(2)]-enkephalin binding in the somatosensory cortex (around -30%). When the dihydropyridine-Ca++ channel antagonist nimodipine was administered alone for 7 days, no significant changes in the density or affinity constant of mu-opioid receptors were observed. However, the chronic and simultaneous administration of nimodipine and sufentanil (7 days), induced a pronounced modification on the density of mu-opioid receptors of the rat central nervous system and blocked the down-regulation observed in sufentanil-treated (tolerant) rats. These neurochemical findings may account for the functional interaction we have observed previously in the analgesic studies between nimodipine and sufentanil. Our data strongly suggest a functional role of L-type Ca++ channels in the mediation of opioid tolerance and super- sensitivity. Volume 274, Issue 3, pp. 1545-1551, 09/01/1995
Copyright © 1995 by American Society for Pharmacology and Experimental Therapeutics




The human neuroblastoma cell line, SH-SY5Y, was used to examine the effects of morphine and the endogenous opioid peptides, endomorphin-1 (EM-1) and endomorphin-2 (EM-2), on mu opioid receptor (MOR) internalization and down-regulation. Treatment for 24 h with EM-1, EM-2 or morphine at 100 nM, 1 μM and 10 μM resulted in a dose-dependent down-regulation of mu receptors. Exposure of cells to 10 μM EM-I for 2.5, 5 and 24 h resulted in a time-dependent down-regulation of mu receptors. Down-regulation of mu receptors by morphine and EM-1 was blocked by treatment with hypertonic sucrose, consistent with an endocytosis-dependent mechanism. Sensitive cell-surface binding studies with a radiolabeled mu antagonist revealed that morphine was able to induce internalization of mu receptors naturally expressed in SH-SY5Y cells. EM-1 produced a more rapid internalization of mu receptors than morphine, but hypertonic sucrose blocked the internalization induced by each of these agonists. This study demonstrates that, like morphine, the endomorphins down-regulate mu opioid receptors in a dose- and time-dependent manner. This study also demonstrates that morphine, as well as EM-1, can induce rapid, endocytosis-dependent internalization of mu opioid receptors in SH-SY5Y cells. These results may help elucidate the ability of mu agonists to regulate the number and responsiveness of their receptors.

here: http://cat.inist.fr/?aModele=afficheN&cpsidt=16253630


Department of Pharmaceutical Sciences, College of Pharmacy and Allied Health Professions, St. John's University, Queens, New York 11439, USA.
Chronic opioid agonist treatment produces tolerance and in some cases opioid receptor internalization and down-regulation. Both morphine and etorphine induce tolerance; however, only etorphine produces mu-opioid receptor (muOR) down-regulation. In vitro studies implicate dynamin-2 (DYN-2) and G-protein receptor kinase-2 (GRK-2) in these processes. Therefore, we examined etorphine and morphine effects on regulation of GRK-2 and DYN-2 in mouse spinal cord. Mice were treated for 7 days with etorphine (200 microg/kg/day infusion) or morphine (40 mg/kg/day infusion + one 25-mg implant pellet). Controls were implanted with a placebo pellet. On the 7th day after implantation mice were tested for i.t. [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) analgesia. In other mice, spinal cord was removed for [(3)H]DAMGO binding studies or GRK-2 and DYN-2 protein and mRNA abundance were determined. Both etorphine and morphine produced significant tolerance (ED(50) shift = 7.6- and 7.3-fold for morphine and etorphine, respectively). Etorphine decreased spinal muOR density by approximately 30%, whereas morphine did not change muOR density. Etorphine increased ( approximately 70%) DYN-2 protein abundance and decreased its mRNA (31%), whereas it had no effect on GRK-2 protein and mRNA abundance. Morphine had no effect on either DYN-2 or GRK-2 protein or mRNA abundance. These data raise the possibility that unequal receptor regulation by etorphine and morphine might be due to differential regulation of trafficking proteins. Overall, receptor down-regulation associated with chronic etorphine treatment may accelerate dynamin-related activity. Finally, the decrease in DYN-2 mRNA may be related to stabilization of DYN-2 protein abundance, which might inhibit transcription.

Not too surprising: different agonists induce tolerance via different mechanisms.


It has been proposed that opioid agonist efficacy may play a role in tolerance and the regulation of opioid receptor density. To address this issue, the present studies estimated the in vivo efficacy of three opioid agonists and then examined changes in spinal mu-opioid receptor density following chronic treatment in the mouse. In addition, tolerance and regulation of the trafficking protein dynamin-2 were determined. To evaluate efficacy, the method of irreversible receptor alkylation was employed and the efficacy parameter tau estimated. Mice were injected with the irreversible mu-opioid receptor antagonist clocinnamox (0.32-25.6 mg/kg, i.p), and 24 h later, the analgesic potency of s.c. morphine, oxycodone and etorphine were determined. Clocinnamox dose-dependently antagonized the analgesic effects of morphine, etorphine and oxycodone. The shift to the right of the dose-response curves was greater for morphine and oxycodone compared to etorphine and the highest dose of clocinnamox reduced the maximal effect of morphine and oxycodone, but not etorphine. The order of efficacy calculated from these results was etorphine>morphine>oxycodone. Other mice were infused for 7 days with oxycodone (10-150 mg/kg/day, s.c.) or etorphine (50-250 microg/kg/day, s.c.) and the analgesic potency of s.c. morphine determined. The low efficacy agonist (oxycodone) produced more tolerance than the high efficacy agonist (etorphine) at equi-effective infusion doses. In saturation binding experiments, the low efficacy opioid agonists (morphine, oxycodone) did not regulate the density of spinal mu-opioid receptors, while etorphine produced approximately 40% reduction in mu-opioid receptor density. Furthermore, etorphine increased spinal dynamin-2 abundance, while oxycodone did not produce any significant change in dynamin-2 abundance. Overall, these data indicate that high efficacy agonists produce less tolerance at equi-effective doses. Furthermore, increased efficacy was associated with mu-opioid receptor downregulation and dynamin-2 upregulation. Conversely, lower efficacy agonists produced more tolerance at equi-effective doses, but did not regulate mu-opioid receptor density or dynamin-2 abundance. Taken together, these studies indicate that agonist efficacy plays an important role in tolerance and regulation of receptors and trafficking proteins.
PMID: 17349996 [PubMed - indexed for MEDLINE]
PMCID: PMC1995431



Although opioid receptors are G-protein coupled, the role that specific G-protein subunits play in the development of opioid tolerance and the regulation of opioid receptor number is not well understood. In the present study, we used a G((i)alpha2) antisense oligodeoxynucleotide (ODN) to examine the contribution of G((i)alpha2) proteins to mu-opioid tolerance and receptor downregulation in the mouse. Mice were injected intracerebroventricularly (ICV) and into the spinal intrathecal space (IT) for 4-5 consecutive days (30 microg/site/day), with an antisense ODN or a mismatch ODN directed at mRNA for the G((i)alpha2) subunit of G-proteins. Controls were treated with dH(2)O. On the second day of ODN treatment continuous subcutaneous (SC) infusion of etorphine (200 microg/kg/day) or morphine (40 mg/kg/day + 25 mg pellet) was begun. Control mice were implanted with inert placebo pellets. Three days later, pumps and pellets were removed and mice were tested for morphine analgesia or mu-opioid receptor density was determined in whole brain. Etorphine produced significant tolerance (ED(50) shift = approximately 11-fold) and downregulation of mu-opioid receptors (approximately 25%). Morphine treatment produced significant tolerance (ED(50) shift approximately 9-fold), but no mu-opioid receptor downregulation. Antisense treatment reduced G((i)alpha2) protein levels in striatum and spinal cord by approximately 25%. G((i)alpha2) antisense reduced the acute potency of morphine. G((i)alpha2) antisense blocked the development of tolerance to morphine treatment and reduced the development of tolerance to etorphine treatment. Antisense did not have any effect on etorphine-induced mu-opioid receptor downregulation. In another experiment, 7-day treatment with morphine or etorphine similarly increased G((i)alpha2) mRNA and protein abundance in spinal cord. Overall, these results support an important role for G((i)alpha2)-protein in the acute effects of opioids and opioid tolerance. However, G((i)alpha2) is not required for agonist-induced mu-opioid receptor density regulation in vivo. Copyright 2002 Wiley-Liss, Inc.
PMID: 12454948 [PubMed - indexed for MEDLINE]


So... Opiates (at least high efficacy agonists- though none of these studies looked at the effects long term administration has on receptor density) reduce receptor density. Receptor density plays a role in tolerance or supersensitivity.

I have full copies for all of these (and within a few weeks they'll be available at wiki.blacklight.in for download) if you'd like to see the actual research, not just the conclusions.

[alowishus]

Just like Hunter in Fear and Loathing, try some human glan, should get ya off nicely.

[alowishus]

Oh sorry didn't mean to stop your fight.....:rolleyes:

[Hammilton]

Oh, btw jacky- I think the psychotridine extract should be available soon; I'm not sure if he's offering it for sale or just sending it out to sample right now. I know he ran into trouble in getting the extract pure, but he is a bit of a perfectionist (I'm assuming he won't sell it unless it's at least 50% pure, but most of his stuff is around 80+% pure). He did have the best Salvinorin A extract I've ever seen- 20mg/ml (in ethanol). Very complicated to measure. It managed to completely break through 8mg of suboxone (though I've seen a study that showed Savinorin A binding to a slightly different pocket of the kappa receptor- there was some overlap. I'd like to like to see a similar study of the binding of herkinorin and 'bromidol' (or a similar 10K-plus x morphine drug).

[red26]

Its threads like this that give you soo much info on whats out there and get yer Kureeousimty boiling over and start eyeballing the acorns that just dropped off that oak across the street. Thanx for this everybody.:D

[stvip]

What a dishonest poser you are. Your argument, repeated many times, was that an increase in receptor density is what causes tolerance.
Quoting you from the aforementioned thread:

You must not understand what a tolerence is. When you were born you were given just so many Mu-opioid receptors in your brain. Everytime you took a codeine or a vicodin, you grew some more, to accomodate the narcotic flooding through your brain. As more grew, you didn't feel as good as you did before they did. Now 10mg of hydro is just filling them all up; there aren't hordes waiting at the gates anymore.

http://forum.opiophile.org/showthread.php?t=5451&page=2

Now you try to pretend your argument was the opposite.

It's unfortunate that it is not grounds for banning, posing as knowledgeable and deliberately spreading misinformation (like you and OxyContinuously do). This is why I decided to curtail my posting in Opiophile.

[OxyContinuously]

What a dishonest poser you are. Your argument, repeated many times, was that an increase in receptor density is what causes tolerance.
Quoting you from the aforementioned thread:



http://forum.opiophile.org/showthread.php?t=5451&page=2

Now you try to pretend your argument was the opposite.

It's unfortunate that it is not grounds for banning, posing as knowledgeable and deliberately spreading misinformation (like you and OxyContinuously do). This is why I decided to curtail my posting in Opiophile.

i purposely stayed out of this arguement, and here u go (again and again) talking shit...ur a failure, man...ur chem knowledge is "high-school"at best, so y don't u go stand in the corner, and let the men talk?

[jacky]

we dont ban people for not knowing exactly what is going on.

from the posts that I have watched over the years of Hammiltons, Oxycont's, and STIV's, I gather that I am less knowledgable than you three opiophiles when it comes to technical pharmakinetics and chemistry knowledge...

probably all of us have perpetrated some spreading of misinformation.

I was hoping at one point to start another forum, possibly private, called rouge research, made of different members who have technical knowledge, and or access to scientific equipment, and or intense drive for the truth and research interest beyond just career interests and or beyond just getting another hit of H or other opiates/opioids.
the website would've not been associated with this one directly...
and possibly some decent headway might have been possible for the creation of various projects into the research of opioid active natural compounds that exist/will be discovered.
I know that this can work, as I have forged some interesting research with others that have technical knowledge, access to interesting natural products, and or scientific equipment for analysis/isolation...this team work resulted in a few interesting experiences for me to say the least.
just the process can be fun.

its a pretty rare opportunity, and I see that personality conflicts are the main hinderance. the next would be money...and interest when research shows little progress.....or preconceptions are shattered.

my main interest in this thread is that a certian zen practitioner slash genius neurosurgeon and theoretical researcher, gives creedence to the bodys own ability to produce help initiate amazing and important realizations and immersions of the mind by its own endogenous opiate cocktails.
I know hashing out the pharmakinetics of HOW this meld of body/mind/consciousness components actually influence/create the immersion experience is a conflict of many interests/opinions, and might not be more important than the ability of some opiates to relieve suffering in humans and other animals.

it makes for interesting reading perhaps, having a mulititude of different subjects going on, and its definitely interesting to some people just based on the bad vibes and drama.....but its not going anywhere really into the zen experience.

I just hope all the banter leads to something true being spoken, I would hate to have stvip stop posting all together just because things get hotly handled.

[Hammilton]

What a dishonest poser you are. Your argument, repeated many times, was that an increase in receptor density is what causes tolerance.
Quoting you from the aforementioned thread:

Whoops, I did get it backwards. It's odd that you never pointed that out and just acted like a jackass the entire time.

I'm not passing myself off as anything. Actually, children like you are the reason I don't post here. I mean, you're upset over an argument from a year ago? You really gotta learn to get over a grudge.

I'm sure I've made much greater errors in the past year or two. You might want to comb through all of my posts to correct all of them. But if you've only come up with two issues (the morphine issue still hasn't been confirmed to occur under natural conditions- so arguing over it is rather pointless) to get upset over, I can live with that.

I've got something like 5K posts at Bluelight and Blacklight in the past year, though. I can pretty much guarantee that I've made much more substantial errors in this time, though.

I have to agree with OxyContinuously, though. For being an 'actual academic researcher' you've got serious deficiencies in your own knowledge. Perhaps this is the source for your anger. I don't know. I don't know what your need to insult others stems from, but I'm sure someone can help you figure it out.

[OxyContinuously]

You know something, "stvip," you're the type of person that always has to start something...you have the insecurities of a molested pre-schooler for crying out loud...

What's your problem anyway? You seem to be on my cock, and I'm wondering why? What do you feel the need to always prove? I purposely stayed out of this thread, even though you were talking complete rubbish, just to see....and sure enough, you had to go and say some nonsense about "OxyContinuously"

Why? What are you, gay? And you don't know how 2 approach me? Haha! Whatever your intention is, you are coming across as a typical ______.

DO you think you're the first "stvip" I've dealt with in my lifetime?

The first "wanna-be" that really has nothing to offer intellectually (and otherwise)?

The first "poser" of sorts that plagiarizes the Wikipedia and "cuts and pastes" his arguements here?

In short, NO...I have plenty of experience with people like you...and honestly there is a lot more I could say--as you are a lot more than what i have said---but unlike you, I practice diplomacy; there's no need for me to talk trash about you on the open forum. I just wanted to bring it to your attention that you are not slick, your chem knowledge is crap, and hopefully now that everyone can see this, you'll be a little embarassed and learn two things called "respect," and more importantly, "humility."

Now be a good little boy, go to your trusted Wikipedia (where you get all your quotes, haha) and figure out what I mean...

Oh, yes, while you're at it, why don't you "acetylize" some morphine with aspirin and make me a batch that has 90 percent yields...

Oh, man, you kill me!

have a nice day:)

[I-Nod]

it makes for interesting reading perhaps, having a mulititude of different subjects going on, and its definitely interesting to some people just based on the bad vibes and drama.....but its not going anywhere really into the zen experience.

Perhaps the gentle tone hid your point...

[covv799ss]

thanks for the interesting post

i read something a while back about monks having higher concentrations of endorphins....will have to look it up