Preventing/reducing opiate tolerance
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Ham-milton
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I read somewhere a while ago of a mu-agonist delta-antagonist analogue of salvinorin.
There was also a drug synthed that combined properties of hydromorphinone and a DOR antagonist. I forget what the latter was. It was shown to cause almost no tolerance.
Ultra-low dose naltrexone has been shown to slow or prevent the development of tolerance. Oxytrex, anyone?
There was also a drug synthed that combined properties of hydromorphinone and a DOR antagonist. I forget what the latter was. It was shown to cause almost no tolerance.
Ultra-low dose naltrexone has been shown to slow or prevent the development of tolerance. Oxytrex, anyone?
rachamim
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Jamshyd: A few like 7-hydroxy-6-tetrahydrocannabinol-1,1-dimethyl... as well as 7 -hydroxy -9...
As for ketamine. ALL NMDA antagonists have the same problem, including the Disassociatives. Olney is one facet, there a few others. I am wondering though, what are you basing the Olney's having been disproven statement on? I am aware of some people who promote Disassociatives in California claiming that they have disproven it but have never seen or heard of anyone who has seen peer reviewed information on it. I am not taking up a cause one way or another, but for general knowledge would love to see the info.
To clarify, I am fully aware of the article by Anderson (fully debunked as pure conjecture) and the book by Jansen that purported to rely on "unpublished reports." Jansen's whole argument rests on rodent metabolism. Sorry Jansen but it is the same metabolism used to quantify most other substances in use and when applied to humans the factors are adjusted. They do not use rat metabolism to conclude probability on humans.
As for ketamine guarding against excito, that is another Jansen claim but either way it would not factor in in discussing other neural damage caused (or purported to have caused) by the substance.
As for ketamine. ALL NMDA antagonists have the same problem, including the Disassociatives. Olney is one facet, there a few others. I am wondering though, what are you basing the Olney's having been disproven statement on? I am aware of some people who promote Disassociatives in California claiming that they have disproven it but have never seen or heard of anyone who has seen peer reviewed information on it. I am not taking up a cause one way or another, but for general knowledge would love to see the info.
To clarify, I am fully aware of the article by Anderson (fully debunked as pure conjecture) and the book by Jansen that purported to rely on "unpublished reports." Jansen's whole argument rests on rodent metabolism. Sorry Jansen but it is the same metabolism used to quantify most other substances in use and when applied to humans the factors are adjusted. They do not use rat metabolism to conclude probability on humans.
As for ketamine guarding against excito, that is another Jansen claim but either way it would not factor in in discussing other neural damage caused (or purported to have caused) by the substance.
phr
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What happened to it?
Right. Does anyone know if there's a study comparing Suboxone vs. Subutex(regular buprenorphine)? Considering the BA of sublingual naloxone, that could potentially count as ultra low dosing and may actually affect buprenoprhine tolerance.
Pharaoh, we're not talking about potentiating.
Ham-milton
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It was just being studied in rats, I don't know if it's ever been tested in humans.
Regarding Olney's Lesions: There's never been anything showing Olney's Lesions in humans, and there's little evidence to indicate they can exist in humans, whether or less be caused by dissociatives.
I'm assuming the only thing you've ever read about it was the "Your brain on dissociatives" and not the subsequent letter from the author admitting it was probably wrong.
I had a friend in Canada who used ketamine extensively and developed brain lesions, which was thought to be the first instance of Olney's Lesions in humans. Later, they were shown to be some other kind of lesions.
There's also really, really good evidence to indicate that Ketamine doesn't even cause brain lesions in rats. They used veterinary ketamine which used a Chloral Hydrate analogue as a preservative that has been shown to cause brain lesions.
This has been covered on BL (I think pretty recently in the ADD subforum), actually. There's a lot of really good info about it.
Regarding Olney's Lesions: There's never been anything showing Olney's Lesions in humans, and there's little evidence to indicate they can exist in humans, whether or less be caused by dissociatives.
I'm assuming the only thing you've ever read about it was the "Your brain on dissociatives" and not the subsequent letter from the author admitting it was probably wrong.
I had a friend in Canada who used ketamine extensively and developed brain lesions, which was thought to be the first instance of Olney's Lesions in humans. Later, they were shown to be some other kind of lesions.
There's also really, really good evidence to indicate that Ketamine doesn't even cause brain lesions in rats. They used veterinary ketamine which used a Chloral Hydrate analogue as a preservative that has been shown to cause brain lesions.
This has been covered on BL (I think pretty recently in the ADD subforum), actually. There's a lot of really good info about it.
rachamim
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Ham:Even if Olney's was the only risk, it would be too much. The data is compelling. however, Olney's is not the only problem. There are 4 others to my knowledge. I am curious though as to how you came to the conclusion that little evidence of Olney's even exists in humans?
"Bran on disassociatives?" What is that?
I base my opinion on 18 years of thorughly researched data that I have spent 15 years lookingh at. While Disassociatives are not my main interest, I was pretty involved with them for a few years, although on the PCP (3 simple routes all with uncontrolled precursors) end. This naturally led me to research into ketamine.
While I obviously enjoy BL immensely, I do not look to it or any other HR/psychoactives site for factual information. I do my best to offer it when applicable but I rely on data, peer reviwed articles and tech journals on issuee slike this. Anecdotal and subjective reasoning will not cut it with me in terms of forming opinions or beliefs.
"Bran on disassociatives?" What is that?
I base my opinion on 18 years of thorughly researched data that I have spent 15 years lookingh at. While Disassociatives are not my main interest, I was pretty involved with them for a few years, although on the PCP (3 simple routes all with uncontrolled precursors) end. This naturally led me to research into ketamine.
While I obviously enjoy BL immensely, I do not look to it or any other HR/psychoactives site for factual information. I do my best to offer it when applicable but I rely on data, peer reviwed articles and tech journals on issuee slike this. Anecdotal and subjective reasoning will not cut it with me in terms of forming opinions or beliefs.
Jamshyd
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And what is that problem that they all share? You say there are 4 of these. Please list them.rachamim said:
I still stand by my original point, that if Ketamine posed serious nurotoxicity, we would have known by now. Its not that new of a drug. Sure, some psychiatric researchers "discovered" that Ketamine might impair memory and what have you. But um... isn't that what all drugs do?
Simply the fact that it was never proven in humans, and strangely enough we haven't seen its effects on responsible users 30 years later...
Jansen is not making his claims in a vaccume. Here is a little sample of published research:
http://www.ncbi.nlm.nih.gov/sites/e..._uids=16583965&query_hl=1&itool=pubmed_docsum
http://www.ncbi.nlm.nih.gov/sites/e...uids=10427397&query_hl=12&itool=pubmed_docsum
http://www.ncbi.nlm.nih.gov/sites/e..._uids=15931866&query_hl=8&itool=pubmed_docsum
Ham-milton
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Did you actually read what I wrote or just the words you randomly decided to?
I'll say it again: There has never been any, not a shred, of evidence to indicate that Olney's lesions have ever appeared in humans.
Part 2: there was evidence to indicate that Olney's Lesions could exist in rats, but that's essentially been shown for what it was: wrong.
A Chloral Hydrate analogue known to cause brain lesions is used as a preservative in some ketamine preperations.
Subsquent studies that compared Ketamine, Ketamine and the Chloral analogue, and the Chloral analogue in rats showed absolutely no indication of lesions in the ketamine group, and lesions in the combo and the analogue group. As I recall, the analogue-only group had the highest rate of lesions.
So, what exactly are these other 4 causes?
And I'll say it one more time: a. Olney's Lesions have never been seen in humans; b. modified studies have shown that ketamine doesn't cause brain lesions, but that a preservative in it does.
This is all coming from journals, not what people are claiming on BL. You can look through ADD for links to those articles. If that's too difficult, I can post them here tommorow afternoon. It's bedtime, get up at 4:30a, work, come home, sleep a bit, and then I'll find them for you if you haven't managed to find them on your own.
Hammilton
I'll say it again: There has never been any, not a shred, of evidence to indicate that Olney's lesions have ever appeared in humans.
Part 2: there was evidence to indicate that Olney's Lesions could exist in rats, but that's essentially been shown for what it was: wrong.
A Chloral Hydrate analogue known to cause brain lesions is used as a preservative in some ketamine preperations.
Subsquent studies that compared Ketamine, Ketamine and the Chloral analogue, and the Chloral analogue in rats showed absolutely no indication of lesions in the ketamine group, and lesions in the combo and the analogue group. As I recall, the analogue-only group had the highest rate of lesions.
So, what exactly are these other 4 causes?
And I'll say it one more time: a. Olney's Lesions have never been seen in humans; b. modified studies have shown that ketamine doesn't cause brain lesions, but that a preservative in it does.
This is all coming from journals, not what people are claiming on BL. You can look through ADD for links to those articles. If that's too difficult, I can post them here tommorow afternoon. It's bedtime, get up at 4:30a, work, come home, sleep a bit, and then I'll find them for you if you haven't managed to find them on your own.
Hammilton
Newmoonrecord
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2 things. (and i havent read the thread so im sorry if it's already come up.
1. There's somebody on opiophile.org that uses dxm all the time (ie every day) to successfully prevent tolerance from forming. Might want to try asking there. (dont remember her name though)
2. The bad news is not in regarding olney's lesions - some new research has come out within the past few months that proves that it was the administration method in rats that was causing them, and that rats subjected to ridiculously high doses orally did not demonstrate any neurological deterioration of that type.
A more rational explanation of the mental deterioration associated with long term dxm use is bromide poisoning (which can be avoided by a simple extraction process with household chems)
1. There's somebody on opiophile.org that uses dxm all the time (ie every day) to successfully prevent tolerance from forming. Might want to try asking there. (dont remember her name though)
2. The bad news is not in regarding olney's lesions - some new research has come out within the past few months that proves that it was the administration method in rats that was causing them, and that rats subjected to ridiculously high doses orally did not demonstrate any neurological deterioration of that type.
A more rational explanation of the mental deterioration associated with long term dxm use is bromide poisoning (which can be avoided by a simple extraction process with household chems)
rachamim
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Jamshyd:
I) Induction of HSP72
II) Regional brain cell death unrelated to vacuoles of any kind
III)NRHypo (hypofunctioning receptor due to the substance(s) in question)
IV) Generalised neuronal/axonal degeneration unrelated to vacuoles
"If these substances posed a serious threat via toxicity, we would have seen it by now." The paper came out when, 89? How would we see a long term result in that short a time? How would it be quantified with lack of proper protocol and other controls?
"Ketamine and memory." I am focusing on purely physical effects although there is something to be said certainly for psychological damage ... No, not all psychoactives cause memory loss,etc. If they did though, how would that make it better in this case?
"Was not proven on humans.." I already adressed that issue but Jamshyd, it was 89 so no, it was not "30 years."
"Jansen in a vacuum and 3 Pubmed papers." I have literally hundreds supporting my postion. Jansen has relied mostly on unpublished (up until now) papers and anecdotal nonsense.
Of the papers, 1 deals only with pediatric anesthesia and how ketamine provides a safe form (I do not believe the "Developing nation" spiel has anything to do with any subject we are talking about so I will not touch it).
The other 2 are merely dealing with excito and a similar phenomenon , something I admitted ketamine DOES provide in a previous post.
In short, all 3 are dealing with in the moment issues, not long term damage which has been my contention (and the contention of evidently thousands of others).
(Edited for spelling, as usual)
I) Induction of HSP72
II) Regional brain cell death unrelated to vacuoles of any kind
III)NRHypo (hypofunctioning receptor due to the substance(s) in question)
IV) Generalised neuronal/axonal degeneration unrelated to vacuoles
"If these substances posed a serious threat via toxicity, we would have seen it by now." The paper came out when, 89? How would we see a long term result in that short a time? How would it be quantified with lack of proper protocol and other controls?
"Ketamine and memory." I am focusing on purely physical effects although there is something to be said certainly for psychological damage ... No, not all psychoactives cause memory loss,etc. If they did though, how would that make it better in this case?
"Was not proven on humans.." I already adressed that issue but Jamshyd, it was 89 so no, it was not "30 years."
"Jansen in a vacuum and 3 Pubmed papers." I have literally hundreds supporting my postion. Jansen has relied mostly on unpublished (up until now) papers and anecdotal nonsense.
Of the papers, 1 deals only with pediatric anesthesia and how ketamine provides a safe form (I do not believe the "Developing nation" spiel has anything to do with any subject we are talking about so I will not touch it).
The other 2 are merely dealing with excito and a similar phenomenon , something I admitted ketamine DOES provide in a previous post.
In short, all 3 are dealing with in the moment issues, not long term damage which has been my contention (and the contention of evidently thousands of others).
(Edited for spelling, as usual)
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gethigh
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well seizures mayb, but think about it, they are partial agonist, there is only a certain amount of receptors for them to agonize, but when u use a large amount of oxycodone, its like a dog to some one's leg, the fuck the shit out of it, and but you fucked up out of ur mind status. as last year, i took 25 50mg tramadol, and it did the same as the 8 50mg i took the day before. well at least thats how i see it.
rachamim
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Ham: "Did Rachamim read Ham-milton's post?" Since I responded point by point I would imagine that it was evident. Just because I do not agree with you does not mean I ignored what you had to say.
"Repeat that there has never been a shred of evidence that the lesions ever appeared in humans." Also not a shred saying they did not, right? We do have pretty good theories on it though. Rats are not humans ( as if rats were the only animals tested for these theories) but, their systems ARE so similar that by calculating the diffirentials in body weight and metabolic processes, we can get a very good estimation, a model that is highly probable.
When predicting future outcomes, that is all we can do. For example, I can hand you a 38 with a single bullet in it and spun, and then tell you you have a 1 in 6 (usually) chance at blowing your brains out, and a 5 in 6 (again usually) chance at walking away. The chance is much greater that you will walk but are you willing to take the lesser odds?
For my 2 shekels I would rather make the safer gamble. A substance that aside from supposedly mimicing NDEs, and some halfway visuals, MIGHT just fry my brain (actually hghly probable). Do I risk it? What is the cost ratio? To me it is not worth it and I also believe in the data that I have examined (literally for years) so I do believe mine is the prudent choice.
Of course I also believe that you should be allowed to make yours. My only goal here is to display as much factual data as possible for those who might not be so sure of themselves so that they might intelligently make up their own minds.
"Chloral hydrate used as a preservative." Is it used in all other Disassociatives? Used in MK and illicit PCP?
"4 causes." Check my previous post please.
"Not coming from people on BL." Well, here is an interesting point. I could just say that I am on BL and it is coming from me but I would rather have others consider it as more than a barb. See, people on BL are usually not trained in pharmacology, physiology, and other concerned sciences ( a couple actually are but many hundreds are not). Most are just users of psychoactives, many using the substance in question. why should anyone take technical advice from them? Trip reports and other subjective nonsense are fun to read but they rarely offer an honest glimpse of a substance.
Thanks for the offer on the articles but I do not think I need them at this point.
(Edited for spelling)
"Repeat that there has never been a shred of evidence that the lesions ever appeared in humans." Also not a shred saying they did not, right? We do have pretty good theories on it though. Rats are not humans ( as if rats were the only animals tested for these theories) but, their systems ARE so similar that by calculating the diffirentials in body weight and metabolic processes, we can get a very good estimation, a model that is highly probable.
When predicting future outcomes, that is all we can do. For example, I can hand you a 38 with a single bullet in it and spun, and then tell you you have a 1 in 6 (usually) chance at blowing your brains out, and a 5 in 6 (again usually) chance at walking away. The chance is much greater that you will walk but are you willing to take the lesser odds?
For my 2 shekels I would rather make the safer gamble. A substance that aside from supposedly mimicing NDEs, and some halfway visuals, MIGHT just fry my brain (actually hghly probable). Do I risk it? What is the cost ratio? To me it is not worth it and I also believe in the data that I have examined (literally for years) so I do believe mine is the prudent choice.
Of course I also believe that you should be allowed to make yours. My only goal here is to display as much factual data as possible for those who might not be so sure of themselves so that they might intelligently make up their own minds.
"Chloral hydrate used as a preservative." Is it used in all other Disassociatives? Used in MK and illicit PCP?
"4 causes." Check my previous post please.
"Not coming from people on BL." Well, here is an interesting point. I could just say that I am on BL and it is coming from me but I would rather have others consider it as more than a barb. See, people on BL are usually not trained in pharmacology, physiology, and other concerned sciences ( a couple actually are but many hundreds are not). Most are just users of psychoactives, many using the substance in question. why should anyone take technical advice from them? Trip reports and other subjective nonsense are fun to read but they rarely offer an honest glimpse of a substance.
Thanks for the offer on the articles but I do not think I need them at this point.
(Edited for spelling)
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Jamshyd
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rachamim said:
Ok, I am honestly interested. Please show me evidence that Ketamine (NOT PCP) does the above. If you post research on that, I'll definitely respect the effort.
I'm talking about reports. The media is more than happy to sound the alarm on anything negative they can associate with drug use. And sure, the paper may have come out in 89, but does that mean that the so-called toxicity only started at that date? People have been using ketamine since the 60s. You'd think a large number of them would have developed one thing or another by now. Instead, I see several Ketamine users who are all brilliant and successful in their lives.
My point was simply that psychiatric testing is unreliable. Psychiatrists spend time and money on reasearch that proves that drugs get you high, after all!
As I said, the drug itself has been used far longer than 89. If it posed a serious risk, many people would have complained by now, and its medicinal use would have been discontinued.
No, you dismissed the excitotoxicity protection thing as "another jansen claim", and the one paper I quoted shows that it is not just jansen.
In any case, even if Ketamine puts holes into your brain, it doesn't seem to have affected anyone negatively for the past 30 years. So perhaps holes in your brain are good for you? I don't know.
rachamim
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Newmoon: "Ask the daily user on Opiophile..." How would she know if she had brain lesions, or better yet, would have them in the future?
"It was administration causing the lesions." Except that there have been at least 8 other papers since Olney on rats alone. Not even counting guinea pigs and rabbits, Olney's administration is not really relevant at this point.
"High doses did not cause it." Please clarify, did you mean Olney administering very high dosages?
"Bromide posioning..." Different cause and effect issue.
"It was administration causing the lesions." Except that there have been at least 8 other papers since Olney on rats alone. Not even counting guinea pigs and rabbits, Olney's administration is not really relevant at this point.
"High doses did not cause it." Please clarify, did you mean Olney administering very high dosages?
"Bromide posioning..." Different cause and effect issue.
Jamshyd
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Well, I actually did a quick pubmed search (as I said, I truly am interested), and found info on points I and III (a total of 3 papers in all).
For point I, this is a "model of psychosis" - again, psychiatric b/s to me. And even if ketamine causes psychosis, this is one psychosis I am happy to live with because it seems to curiously allow me to be more functional person in society, free of manic-depressive debilitation and anxiety - and that is an effect that lasts for a long time after I stop taking the drug (I take it in daily sub-psychotropic doses, month on - month off).
For point III, both researches involve other drugs, and both are in pigs. In addition, if I understood correctly, this induction is completely dependent on the injury of hepatic nurons.
I was unable to reasearch points I and II because they don't include specifics, which I hope you'd mention.
For point I, this is a "model of psychosis" - again, psychiatric b/s to me. And even if ketamine causes psychosis, this is one psychosis I am happy to live with because it seems to curiously allow me to be more functional person in society, free of manic-depressive debilitation and anxiety - and that is an effect that lasts for a long time after I stop taking the drug (I take it in daily sub-psychotropic doses, month on - month off).
For point III, both researches involve other drugs, and both are in pigs. In addition, if I understood correctly, this induction is completely dependent on the injury of hepatic nurons.
I was unable to reasearch points I and II because they don't include specifics, which I hope you'd mention.
rachamim
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Jamshyd: I do not want to get into another multi day combative thread but Number I is organic in nature. Psychological is psychological but it has an organic source, right?
If you would like, of course I will send you info on the other points, etc. Just give me some time because I am backed up big time (sounds like a BM problem, about as much fun). It is the beginning of rice season and i am spending a bit too much time on this. Please, if I forget (often happens), please let me know by whatever measn in 2 days. I will try to do it later today (230 PM here now) but if not, it could escape me.
If you would like, of course I will send you info on the other points, etc. Just give me some time because I am backed up big time (sounds like a BM problem, about as much fun). It is the beginning of rice season and i am spending a bit too much time on this. Please, if I forget (often happens), please let me know by whatever measn in 2 days. I will try to do it later today (230 PM here now) but if not, it could escape me.
rachamim
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Want t clarify that point about psychological, I mean that the substace(s) create a organic condition that leads to psychological symptoms. Do not know if it is clear because all psychological conditions caused by a psychoactive substance could rightfully claim to be organic in nature if one wanted to split hairs. Hmmm...Better just send you the papers on it.
Newmoonrecord
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rachamim said:
1. I was referring to the gal on opiophile because she would probably be able to give the OP an informed idea based on extensive experience, something that the people here might not have. Wasnt talking about lesions.
2. I was referring to http://dx.doi.org/10.1016/j.neuro.2007.03.009 The study in 2007 which showed that oral doses to rats do not produce olney's lesions. But alas i just remembered that olney never even gave rats dxm. Oh well. The 2007 study is still useful.