New Methadone Potentiation - A Vickers Method

[Valentine4]

New Methadone Potentiation Method, Gastric Emptying

Vickers Methadone Potentiation Method

Abstract:

​

Oral Methadone is potentiated by the oral consumption of Ginger (or anything inducing gastric emptying) following the consumption of Methadone. This is due to the poor absorption and degradation of methadone while in the stomach versus the efficient absorption of methadone in the intestines. This is furthered due to the fact that methadone itself delays gastric emptying. Accordingly in decreasing gastric emptying time, Ginger will decrease the time for onset of both clinical and physical effects.
(note: alcohol is another effective chemical, but is to be avoided due its negative physiological effects and contraindications specific with opiates)​

Basis:

Methadone absorption is the primary basis for this novel method of Methadone potentiation. Methadone is poorly absorbed by the stomach and duodenum, significant bioavailability is only achieved once the Methadone has entered the lower GI tract, primarily the intestines.

Methadones own physical effects further weaken its own absorption, as methadone itself has the effect of delaying gastric emptying. Additionally, the longer the Methadone remains in the stomach, the greater adverse ratio degradation to absorption (The longer it is in the stomach, the more the chemical degrades, while very little absorption occurs); signifigantly weakening the efficiency before Gastric Emptying occurs(less of the chemical is now available to be absorbed in the intestines).​

These concepts are more clearly explained by [1]:

The absorption of dl-methadone from the gastrointestinal tract of the Sprague-Dawley rat was examined by the in vivo segment technique. Duodenal absorption, measured as a function of time and dose, followed first-order kinetics with a half-life of 15.6 min. Absorption was not influenced by prior or concomitant administration of a variety of drugs. Absorption from other regions of the intestine was similar to that from the duodenum; in contrast, absorption from the stomach was markedly slower. Gastric absorption was increased by alkalinization of stomach contents but was still considerably slower than from the duodenum. Gastric emptying of methadone appears to be the rate-limiting step in the overall gastrointestinal absorption of the drug, since the rate of emptying following intubation of the drug into the stomach was also considerably slower than the rate of duodenal absorption.

Mechanism of Action:

As explained by [1], the faster the methadone enters, the greater the efficiency and bioavailbility becomes. E.g. Methadone is stronger the faster it makes its way into the intestines. Therefor, any mechanism that can induce Gastric Emptying will increase the effectiveness of methadone consumed orally beforehand. So an effective potentiator of methadone would be any chemical inducing rapid gastric emptying, without negative interactions and contraindications. Ideally this catalyst for this should be easily available, and warrant little concern for societal reasons.

The logical choice was Ginger. Ginger has a myriad of known beneficial Gastro-Intestinal effects, and is a known primarily as an antiemetic. It has also been shown to greatly increase the rate of Gastric Emptying as illustrated by the following two studies:​

[2]

Ginger has been reported to improve upper gastrointestinal symptoms. Little information about the effects of ginger on gastric motor function, exists, however. Our aim was to investigate the effects of ginger on gastric emptying, antral motility, proximal gastric dimensions, and postprandial symptoms. METHODS: Twenty-four healthy volunteers were studied twice in a randomized double-blind manner. After an 8 h fast, the volunteers ingested three ginger capsules (total 1200 mg) or placebo, followed after 1 h by 500 ml low-nutrient soup. Antral area, fundus area and diameter, and the frequency of antral contractions were measured using ultrasound at frequent intervals over 90 min, and the gastric half-emptying time was calculated from the change in antral area. Gastrointestinal sensations and appetite were scored using visual analog questionnaires. Data are expressed in terms of mean+/-standard error. RESULTS: Antral area decreased more rapidly (P<0.001) and the gastric half-emptying time was less after ginger than placebo ingestion (13.1+/-1.1 vs. 26.7+/-3.1 min, P<0.01), whereas the frequency of antral contractions was greater (P<0.005). Fundus dimensions did not differ, and there was no significant difference in any gastrointestinal symptoms. CONCLUSION: Ginger accelerates gastric emptying and stimulates antral contractions in healthy volunteers. These effects could potentially be beneficial in symptomatic patient groups.

[3]

Cisplatin causes nausea, vomiting and inhibition of gastric emptying. We have demonstrated the antiemetic effect of the acetone and ethanolic extract of ginger (Zingiber officinale, Roscoe, Zingiberacae) against cisplatin-induced emesis in dogs. In the present study, the acetone and 50% ethanolic extract of ginger in the doses of 100. 200 and 500 mg/kg (p.o.) and ginger juice, in the doses of 2 and 4 ml/kg, were investigated against cisplatin effect on gastric emptying in rats. All three ginger preparations significantly reversed cisplatin-induced delay in gastric emptying. The ginger juice and acetone extract were more effective than the 50% ethanolic extract. The reversal produced by the ginger acetone extract was similar to that caused by the 5-HT3 receptor antagonist ondansetron; however, ginger juice produced better reversal than ondansetron. Therefore, ginger, an antiemetic for cancer chemotherapy, may also be useful in improving the gastrointestinal side effects of cancer chemotherapy.

Thus Ginger, being an effective gastric emptier, is also an effective potentiator of the drug Methadone. This is via increased rates of absorption, thus leading to greater bioavailability. Accordingly it will decrease the time for onset of both clinical and physical effects.​

Summary and Experimental Results:
From firsthand experience this author can provide annecdotal evidence that this method does indeed work. Multiple trials were conducted at various doses giving clear results; there was a clear linear dose to effect response, attenuated by a ceiling effect at an apparent peak dose. No negative side effects were experienced even at highest dose. This experimenter used standardized vegetarian Ginger capsules, 250 mg each.

The multiple trials were spaced far apart enough to allow clearance of methadone and ginger from the system (look up plasma levels and half-lives of methadone and ginger for more information). Addiotnal time was allowed to hopefully avoid interference in results via tolerance, but due to contraints less than a week was possible between trials. While this may have skewed results due to an increased tolerance to both since the methadone dosage remained the same; the results only show that if their is in fact a Ginger tolerance, its effectiveness still increased with dose despite this.

The different dosages were (in mg): 250, 500, 750, 1000, 1500, 3000, 4500, and 6000. (The high range doses are not recommended for a body unaccustomed to Ginger despite finding no negative effects)​

-Experimental Data-

Every dose up to 1500 subjectively appeared to increase the overall strength in clinical effects of the methadone: Decreased Respiration, Euphoria, Impaired Motor Skills, Impaired Cognitive Function Etc.

After 1500, the increase in strength seemed to drop of at 4500. But while the strength potentiation leveled off, the decreased time of onset never did.

Normally methadone does not peak for the experimenter until 3 hours (this caries by user).

This was reduced significantly at 1000, to 1.5 hours.

It was further reduced to approx. 1 hour at 4500.

At 6000 it felt to only take 30 minutes.

(onset times were also reduced proportionately, normal onset is 1.5 hours)​

-Conclusion-

Clearly this data shows that for this experimenter, Ginger is not only a potentiator of the strength of methadone, but a even more effective time-to-onset and time-to-peak clinical effects. Ginger potentiates Methadone, and should also potentiate other drugs with low bioavailability via the stomach but with good bioavailability via the intestines.​

Disclaimer:

This is a scientific study, not intended for emulation, repetition, or a human drug usage guideline. This document may be reused without permission for any purpose, scientific or other, only if correct citation to the author is correctly provided. The author takes no responsibility for the claims of this experiment, and any use of this experiments concepts or results is strictly the responsibility of the end user. These results are not guaranteed, nor is the experiment recomended to be conducted by others. Unknown drug mixtures can produce unknown health risks. High doses of any drug are always risky, human experimentation is never recommended, and never condoned.​

Everything in moderation.



[1] Drug Metab Dispos. 1975 Nov-Dec;3(6):525-9.
The gastrointestinal absorption of methadone in the rat.
Walsh CT, Levine RR, Squires C.

[2] Eur J Gastroenterol Hepatol. 2008 May;20(5):436-40.
Effects of ginger on gastric emptying and motility in healthy humans.
Wu KL, Rayner CK, Chuah SK, Changchien CS, Lu SN, Chiu YC,
Chiu KW, Lee CM.

[3] Journal of ethnopharmacology ISSN 0378-8741 CODEN JOETD7
1998, vol. 62, no1, pp. 49-55 (24 ref.)
Reversal of cisplatin-induced delay in gastric emptying in rats by ginger

 

[Valentine4]

Also for my first theory on Suboxone Potentiation, please read the following link: http://www.bluelight.ru/vb/showthread.php?t=347629 .

I will soon be updating and modifying that theory base don new research and experimental data.

 

[rachamim]

Well, I admire your iniative but a couple of things that are working against you. Really 3 things.

I) Oral methadone already has an extremly high bioavailability at 80 to 87% depending on the protocol and as such, there is no real need to potentiate it. It does what it is designed to do, very well.

II) It does NOT produce euphoria, under any circumstances. It is chemically impossible.

III) The advantage gained by instigating more rapid onset (because in the end, it is not going to increase bioavailability anyway, only onset which is a huge world away from the claim), and onset is highly subjective and not really a worthwhile goal in a substance that has average onset (orally that would be 45 minutes, a trait shared by almost oral medications)


I want to add, I really do admire the iniative, but have to point out in a helping way that to make a claim of more promounced respiration you have to actually test it and not offer a subjective expression.

 

[The Monkey Mantra]

Rachamim: It's chemically impossible for methadone to produce euphoria? What does "chemically impossible" mean? And under any circumstances, no less? It's a pretty decently strong mu-agonist, so I beg to differ, defer, and then differ some more. Methadone produces a fairly strong euphoria, especially in opiate-naive patients or those who especially like narcotics. I personally dig the stuff, and find it offers a considerable mood boost.

 

[rachamim]

OK, all moderate to heavy opiates/opioids are subject to a Golden Rule known as "The Morphine Rule." Without spitting out the rule, I will condense it thus: In order to produce euphoria a substance needs to have a quaternary carbon atom connected to a tertiary nitrogen atom (CH2-CH2 + N3). Mu Agonism, specifcally Mu2 is a feature of euphoric potential but it requires a synergistic component (that which I just illustrated).


"Euphoria" in the psychoactive sense denotes soemthing other than heavy sedation. Methadone, just like any other moderate to heavy opiate/opioid produces sedation. Indeed methadone is probably the most sedating but most addicts want a true euphoria.

(Edited for spelling, ahhh, I hate English)

 

[Valentine4]

II) It does NOT produce euphoria, under any circumstances. It is chemically impossible.

III) The advantage gained by instigating more rapid onset (because in the end, it is not going to increase bioavailability anyway, only onset which is a huge world away from the claim), and onset is highly subjective and not really a worthwhile goal in a substance that has average onset (orally that would be 45 minutes, a trait shared by almost oral medications)...

...I want to add, I really do admire the iniative, but have to point out in a helping way that to make a claim of more promounced respiration you have to actually test it and not offer a subjective expression.

Your telling me that Methadone does not produce euphoria? I would guarantee you countless people on this forum would disagree with you. Here's several respected scientific studies that disagree with you, I found dozens:

Aust N Z J Public Health. 2002 Aug;26(4):358-62; discussion 362-3.
Fatal methadone toxicity: signs and circumstances, and the role of
benzodiazepines.
Caplehorn JR, Drummer OH.

...Methadone contributed to the deaths of 57 of the 87 adult coronial cases in which it was detected in NSW in 1994. The most commonly reported early signs of severe methadone toxicity were ataxia, slurred speech and evident euphoria....

Drug Alcohol Depend. 1986 Jul;17(4):301-10.
Comparison of intravenously administered methadone, morphine and heroin.
Jasinski DR, Preston KL.

...Morphine-like physiologic, subjective and behavioral effects were measured periodically for 24 h after drug administration. Under the conditions of the experiment methadone produced a profile of effects which was indistinguishable from that of morphine and heroin. Only the time course of miosis, which was longer lasting following methadone, differentiated among the three compounds. The relative potencies of methadone, morphine and heroin for the initial 5 h of effect were constant over all opiate-like effects, including measures of euphoria...

Sorry, but if your going to criticize someone, make sure you know what your talking about.

onset is highly subjective and not really a worthwhile goal in a substance that has average onset (orally that would be 45 minutes, a trait shared by almost oral medications)

You say that onset is subjective. But you say its not worthwhile goal...that is a subjective statement as well.

And why would it not matter if you have to wait 3 hours vs 30 minutes for methadone to take effect? Surely that does matter. The quicker a person in withdrawals can feel well again is very important. Or the quicker a person can feel euphoria the better too.

Don't attack my alleged subjectivity with your subjective opinion. If you wish to criticize my science please do.

Oh and by the way please double check your methadone bioavailability figures as well. You gave quite a subjective number that you seem to have pulled out of your head

Clinical Pharmacokinetics. 41(14):1153-1193, 2002
Interindividual Variability of the Clinical Pharmacokinetics of Methadone: Implications for the Treatment of Opioid Dependence
Eap, Chin B. 1; Buclin, Thierry 2; Baumann, Pierre 1

Methadone has a mean bioavailability of approximately 75%, but values between 36% and 100% have been described.

Ok so I feel, subjectively, I have more than disqualified your comments. But if you have a problem with my theory I would really like to know, thanks!

 

[Valentine4]

II) It does NOT produce euphoria, under any circumstances. It is chemically impossible.

I just have to reiterate that the above quote is completely inaccurate. I think you misunderstand how opiates produce euphoria. Methadone binds to all the right opiate receptors to produce euphoria; including specifically the µ (mu) receptor which produces most of the euphoria. And its agonist activity at the µ receptor is quite strong, as is it binding affinity.


And by the way, someone VERY close to ME finds methadone to be his favorite opiate, and extremely euphoric. The only problem he encounters with it, is that for some reason it makes him extremely manic and hyper. But the overwhelming sense of well being and contentedness is amazing.

 

[rachamim]

OK, you have an avid interest and I like that. Surely, you have heard of the seminal 1967 paper that claimed LSD caused permanant genetic damage? It was Bullshi@. See, the 2 papers you just referenced do not deal with euphoria it is listed as an aside and is not challenged, only the paper's actual findings are up for challenge.


Peer Review does not mean you are right, only that it is worth scrutiny by the community at large.

Now, on euphoria. As I explained, Mu2 Agonism is not what causes euphoria BUT IS neccessary for it to take place. Read what I wrote a bit slower, internalise it. Then, if you still differ which somehow I imagine you will, research what I pointed out and then challenge not from your subjective experiences but from actual clinical research. I will try to remember this thread and then answer you once you have done that, ok?


Again, I am not putting you down, indeed I applaud you interest.

 

[Valentine4]

Please explain how chemically methadone cannot produce euphoria. Because according to its binding properties it is a drug that should produce a strong linear dose dependent euphoria.

You say that methadone is not euphoric at all, yet all of us who have experienced it clearly find it euphoric; which would agree with its pharmacological properties.

I'm gonna have to have k'd out in az come in here an educate you on methadone I think.

I don't care what your intentions are, you are wrong and give no eveidence to the contrary. You sound like one of the doctors who don't realize that suboxone, tramadol, and methadone all have strong abuse potential due to their euphoric properties. Most of all methadone.

And if you are going to cite chemistry "quaternary carbon atom connected to a tertiary nitrogen atom (CH2-CH2 + N3)" you need to explain why, or cite a source that can. because that chemical compound is not in anyway a substitute for reason.

But on that subject: Methadone ctually does reach that qualification that you sighted for euphoria, but that is not a requirement for euphoria.

The Structure of Morphine
Chemistry of the totally or partially synthetic analgesics
Ph.D. Paul B. Weill
D.Sc. Ulrich Weiss

The presence of a quaternary carbon linked through -C-C- with the amino-nitrogen has been noted hitherto in analgesics in the morphine, pethidine and methadone series. Its presence, and the relationship to nitrogen described above, might not be absolutely necessary, but at least they seem to be responsible for the maximum intensity of the analgesic effect.

Is it funny to you, that you were wrong on everything?

I simply can't stand know-it-alls, especially the kind that don't know what they are talking about.

 

[rachamim]

Sorry for not answering the other points you made. On subjectivity and my stating that onset is not worthwhile. Well you COULD argue that but you are missing the whole point. The fact that you include a subjective value in a proposed paper (which I gather this is) is not something you ever want to do in a paper/study. Subjective values are worthless and by your pointing out that my telling you that is in fact subjective further proves my point. You dismiss my telling you, but in doing so dismiss your own point to begin with. I hope it is not seeming as if I am trying to run you in circles, I am not.

You porposed the idea, in the form of a paper, and I hoping to help you . IF you really wish to pursue the idea you need to learn about proper trials and clinical standards, such as blind trial and double blind, etc. The fact that you and a mate take ginger caps and believe it has a faster onset is not going to work outside of soem very young and/or very deparate folks.


The thing with potentiation, it is an easy gambit. We already know that anything utilising the same substrate will obviously potentiate . A substance causing more rapid digestion, even in a theoretical sense, is not going ot make a discernible difference with a substance that already has absolutely average onset and super oral bioavailaibilty. You see?

Either way, good presentation and idea, and of course you are doing better than 99% of the folks here in that you really seem to be trying to follow through with an idea.

(Edited for spelling, as always)

 

[rachamim]

First, I was here when K'd made his first post on the site, ask him he will know who I am very well. Ask him about the time he tried to "educate" me about how I was wrong that it is UNSAFE to mix Benzos and alcohol. I like him though, and it is not meant to disparage him, that was years ago, but rather to teach you in a manner of speaking.

Secondly, you are ignoring the information I gave you and are arguing entirely on partial information combined with your subjective experiences. IF you value subjective experiences, I am 41 and have been on methadone more or less consistently since about age 21. Of ALL the people on the site, I am not the one you are going to really wish to argue with in terms of methadone.


That said, I am not infallible, if you find something that directly challenges what I have told you, I would love to discuss it. Please start with basics though. You do not seem to even be aware of the "Morphine Rule" much less what failure to conform on any of the axioms would mean in terms of psychoactive or even basic pharmocological potential.


"Double check my bio. numbers which I seem to have pulled out of my head." Qute right, first thing you have nailed. I DID pull it out of my head because I have actually been participating in studies concerning the substance perhaps before you were even born. I wish I could tell you you were absolutely correct all around. I certainly would not dismiss an actual improvement to any substance, much less one that afforded me stability for the better part of my adult life.


However, no need to check my own figures. I only provide information I am factually certain of. I do encourage you though, to check anything I tell you because this will aid you in learning. You should NEVER take anything , especially off of the internet at face value. So by all means, I hope you WILL check all my information.

Ahhh, I see at the end that you are getting very snippy. I am not trying to "make fun" of you, instead it is better to actually learn rather than just repeat untruths.

(Edited, once again, for spelling)

 

[Valentine4]

However, no need to check my own figures. I only provide information I am factually certain of. I do encourage you though, to check anything I tell you because this will aid you in learning. You should NEVER take anything , especially off of the internet at face value. So by all means, I hope you WILL check all my information.

You have to be kidding me. "I'm so smart, that i don't need sources."???????
I've already disproved everything you said. Good Night.

You should NEVER take anything , especially off of the internet at face value. So by all means, I hope you WILL check all my information.

I have disproved every word you said. And I did not get my information from the internet, nor did i make it up in my head like you did.

You just keep annoying me by mis-educating people and trying to act pompous and arrogant with the defense that:

Summary of you: well you got that from a source, i got mine from my head. I know im right, even though a renound scientists say im wrong

Please at least attempt a logical defense of yourself.

What I am giving you is not from the internet, I actually cite my sources, you can see them above too:

The Drug Metabolism Disposition

The European Journal of Gastroenterol Hepatology

The Journal of ethnopharmacology

Australian and New Zealand Journal of Public Health

Drug and Alcohol Dependence Journal

The journal of Clinical Pharmacokinetics

UNODC Bulletin on Narcotics


Im not pulling things of the internet as you imply

defend your criticism on my theory with scientific reason. spouting off life lessons doesn't matter. I simply want to have an educated discussion and you come in here pretending to know things and tring to sound smart by saying things that are untrue, bothers me.

Your defense was that the scientific journals and the authors who were published in them were wrong, and you are right because you say so. Great defense.

 

[Valentine4]

Please go troll somewhere else if you arnt going to accept that the scientist im citing have proven you wrong, I dont want a flame war. I just want you to not lie to people about things.

 

[rachamim]

"So smart I do not need sources.": How would you ever infer that from what I actually posted? I did not say that I am above sources. I SAID that I already factually know what the oral bio. of methadone is. It is asimple number with 2 digits. If you need to source that, you should not be thinking about papers.

"Go troll.": Fair enough, I will not post in YOUR thread anymore but you should know just what a troll is before you call someone the name. You have what? Less than 10 posts here in a one year period? Try sticking around, assuming you have not been, and get to know people and then try to make judgements on their worth. The fact that you make snap judgements like that is completely predictable given your contributions thus far.


This is NOT yourBL Jorunal, nor is it a blog. It is a thread in a forum that invites discussion. If you cannot accept constructive criticism, you really might wish to reevaluate your presence here. It is not about grandstanding but rather it is about accurate infromation. Simply and politely put, yours is grossly inaccurate. I tried to be constructive and tell you in a civil manner but to you that is "Trolling."

It is also not a flame war unless you are merely counting your own end. A "War" takes 2 people. I have been and remain entirely civil to you. I never criticised you as a person, never tossed ad hominems at you, merely dared to differ with your information and that of course is the nature of this forum.


I "annoy" you? Sounds more like a problem you need to work out than anything I can possibly say or do. A person who purports to offer a scientific finding who then gets obviously upset when challenged on his "findings" is not going to go far at all.


Nobody "implied you pull things off the net." AGAIN, you need to read my post slowly. I said you should not believe me at face value, rather that you should actually research what I am telling you.

Again, if you learn civility I will be glad to help you in the future...


Here is my last tip, REPEATED since you obviously have not taken it to heart yet, RESEARCH THE MORPHINE RULE.


(Edited for spelling)

 

[fastandbulbous]

I'm curious as to how methadone degrades in the stomach as it is chemically very stable and I can't see how either 0.1M hydrochloric acid or proteases will cause it to degrade.

OK, all moderate to heavy opiates/opioids are subject to a Golden Rule known as "The Morphine Rule." Without spitting out the rule, I will condense it thus: In order to produce euphoria a substance needs to have a quaternary carbon atom connected to a tertiary nitrogen atom

The thiambutenes are heavy duty opioids that have a big euphoria component and don't fit the rule. Apparently etonitazene is as well and it doesn't quite comply either (actually none of the fentanyls do either)

As to the rest, everyone play nicely or I'll be forced to slap wrists

 

[MurphyClox]

OK, all moderate to heavy opiates/opioids are subject to a Golden Rule known as "The Morphine Rule." Without spitting out the rule, I will condense it thus: In order to produce euphoria a substance needs to have a quaternary carbon atom connected to a tertiary nitrogen atom (CH2-CH2 + N3). Mu Agonism, specifcally Mu2 is a feature of euphoric potential but it requires a synergistic component (that which I just illustrated).

That said, I am not infallible, if you find something that directly challenges what I have told you, I would love to discuss it. Please start with basics though. You do not seem to even be aware of the "Morphine Rule" much less what failure to conform on any of the axioms would mean in terms of psychoactive or even basic pharmocological potential.

Sorry, but the 'morphine rule' is definitively outdated. Simple derivatives of salvinorin are known to act agonistic at the µ-receptor. They don't even contain a nitrogen! And also don't forget the whole fentanyl-group, which doesn't follow the 'morphine rule' as well.

Agonist opioids INDEED cause euphoria, and you don't need a randomized double-blind trial, because substances like methadone, heroine and morphine are 'field tested'. This means that so many people tried it that one can take all those subjective reports into account. The huge mass of experienced evidence just proved that in most people (but not in all) opioids DO cause euphoria. Some more, some less.

Peace! Murphy

Edit: I just saw that FnB already mentioned the fentanyls...

 

[MurphyClox]

As to the rest, everyone play nicely or I'll be forced to slap wrists

Then let my try play nicely by proving some of my statements with a ref:

"Functional magnetic resonance imaging measures of the effects of morphine on central nervous system circuitry in opioid-naive healthy volunteers."
Anesthesia & Analgesia 2006, 103(1), p.208-216.

Abstract

In this pilot study, we used functional magnetic resonance imaging (fMRI) to study the effects of morphine in 8 healthy, opioid-naive volunteers. I.v. small-dose morphine (4 mg/70 kg) or saline was administered to volunteers undergoing a fMRI scan. Infusion of morphine, but not saline, elicited mild euphoria without aversive symptoms and resulted in pos. signal changes in reward structures including the nucleus accumbens, sublenticular extended amygdala, orbitofrontal cortex, and hippocampus. The pos. signal in the accumbens was opposite to the signal previously reported for noxious stimuli. Morphine produces a decreased signal in cortical areas in a similar manner to sedative-hypnotic drugs such as propofol or midazolam. Activation in endogenous analgesic regions was obsd. in the periaqueductal gray, the anterior cingulate gyrus (decreased signal), and hypothalamus (increased signals). The pattern of activation in reward circuitry was similar to that reported for euphoric drugs of abuse, providing a model to evaluate the initial effects of morphine on the central nervous system components of the circuitry involved in addiction. The segregation of fMRI response that was obsd. in cortical vs. subcortical regions suggests a dissocn. of reward from sensory-motor and cognitive functions. Activation patterns were opposite to those previously obsd. for the m antagonist, naloxone.

So,
1. Opioids induce euphoria. Period! This explicitly includes methadone as well.
2. Euphoria and sedation do not necessarily exclude each other.

Peace! Murphy

 

[MurphyClox]

Some more?

"Opioid receptor polymorphisms and opioid abuse."
Lee, Nancy M.; Smith, Andrew P.
Pharmacogenomics 2002, 3(2), p.219

Abstract

A review. The sequencing of the human genome is only the first step. The next step is to det. the function of these genes and in particular, how alterations in specific genes lead to major human disorders. Many labs. are now focusing on identifying and characterizing single nucleotide polymorphisms (SNPs), to det. which correlate in frequency with certain population groups who may be particularly susceptible to certain diseases. The µ-opioid receptor (MOR), which mediates the clin. important analgesic effects of drugs like morphine as well as the euphoria sought by heroin abusers, exhibits several dozen polymorphisms. Several of these are assocd. with altered receptor function and individuals at risk for drug abuse.

 

[fastandbulbous]

Then let my try play nicely by proving some of my statements with a ref:

You always play nicely!

 

[rachamim]

Actually Fast I should ammend that and I am glad you caught that because there are substances that fall outside the rule. However, methadone is certainly not one of them. It is important though to be accurate and this IS true.

As I had told the OP euphoria is a synergistic, cumalitive response that requires cooridinated input (although I simplified it and did not mention input which is an obvious inference). Other vital aspects that need to be considered and these of course apply to all other substances outside the Rule's parameters, are endogenous opioids and their interaction with the outside substance, cAMP levels,action potential levels, ventral tegmental interaction, polymorphism which is not only quite possible but is also incredibly varied, and so on. Then there are dozens of other issues to be examined.

I have to say though, you really consider Thiambutenes to be heavyduty? The entire chain only mazes out at 1.3 X morphine and that is a fluke. Most are weak along the lines of meperidine.


I have to say hats off though on the Benzimidazoles, give it to the FSU to lab up etonitazene. This is the nation that produced "Jeff" after all and are always cutting edge, the best minds in the world hands down. The only illicit methadone lab known to man! Highsmith was supposed to be so addicited that he had to kill himself when methadone could not sate his jones after the bust! I say the US, as much as I hate it, does give the FSU a run though.

Ahhh, but I like slapped wrists!

While I did say that I would not post in the thread, I think that I will ammend that as well and simply say that I will not longer address the OP out of respect for his/her wishes.