New Methadone Potentiation - A Vickers Method

[rachamim]

MurphyCox: "Morphine Rule is Outdateted." Do not tell me, tell the world of science. Your mentioning Mu mediation is not pointing to anything. It is a complex organic process in which a substance can or cannot have a great mediating effect overall, as with the chemical rule I illsutrated.

I also pretty much answered that more explicitly in my previous post directed to Fast so I will not continue pounding the nail.

"You do not need a field trial because substances are field tested.": WHAT? Are you serious? It is called science. Subjectivity is completely worthless. What you, your mate, or 100 BLers is not going to overturn chemical improbabilities. Your supposition that the Rule is outdated is non-sensical because methadone is a comparatively old substance and is tried and true against it. Its euphoric properties were complete quantified before even my birth.

Murphy's 2nd Post: "Opioids produce euphoria!.": Really? I did not see that I had EVER said they did not. I said methadone did not (as well as some others although I did NOT mention it).

What other opioids/opiates do or do not do has no bearing AT ALL on any particular substance, only in terms of a class generalisation. A common opioid attribute IS euphoria but just as structure is not a universal facet, neither is a unified organic interation.

"Paper in 2nd post.": No offence but what odes the paper have to do with the price of tea? It is completely pointless to post it if you are trying to porove methadone is euphoric.

Murphy's 3rd and last post": I do not want to make YOU angry but again, that is talking about a generlisation that is not found in every substance within the class. This is basic 101 stuff and it is almost embarrassing to be pointing it out.


See, this is exactly what happens when a substance people are fond of is called into question in ANY way. YOU love methadone, you find it euphoric and that causes you to take offence that I could claim otherwise, it seems to you that it questions your judgement. It should not matter to you. The thing that matters, is that it feels the way you claim TO YOU. Do not try to convince me because as I said, it has been a bit more than 2 decades since I became acquinated with the substance as a consumer let alone in clinical work-ups.

 

[Tchort]

. . . 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)

Gastric absorption was increased by alkalinization of stomach contents

Would consuming substances to make the stomach environment more alkaline prior to consuming Methadone/Ginger further potentiate the effect?

Also, would consuming an additional CYP2D6 and/or CYP3A4 Inhibitor at the time of M/G ingestion further enhance the subjective physiological effects of the Methadone by slowing down its metabolism?

 

[MurphyClox]

Murphy's 3rd and last post": I do not want to make YOU angry but again, that is talking about a generlisation that is not found in every substance within the class. This is basic 101 stuff and it is almost embarrassing to be pointing it out. [1]


See, this is exactly what happens when a substance people are fond of is called into question in ANY way. YOU love methadone, you find it euphoric and that causes you to take offence that I could claim otherwise, it seems to you that it questions your judgement. It should not matter to you. The thing that matters, is that it feels the way you claim TO YOU. Do not try to convince me because as I said, it has been a bit more than 2 decades since I became acquinated with the substance as a consumer let alone in clinical work-ups. [2]

[1] No prob, to make me angry it takes a bit more,

[2] Yo pal, stay calm. First, I do not love methadone. That is, because (honestly) I have never tried it. Nor did I taste heroine or morphine. My opioid-experiences are in fact quite limited. That's why I tried to argue with facts; facts published in peer-review articles because those are considered to be the scientific truth. I'm quite sorry that you're still doubting it...

Please don't tell me or other members here that personal (subjective!) experiences do not count when it comes to draw conclusions, because one of your main arguments is your personal experience. I think you cited now 2-3 times your 20 years experience with methadone. What that's experience worth? Sorry to say so: Nothing!! You are citing a sample size of n=1 (yourself), while I was trying to point out that thousands of personal experiences are again worth considering. In pharmaceutical industry this is called (inofficially IMO) 'Phase IV' of a compounds trial. You have really a hard stand against numerous of people who have taken methadone and admitted that it indeed creates euphoria. And this IS actually scientific to do so.

Subjectivity is completely worthless.

Nope...it isn't when sample size has reached a certain number. And with methadone it definitively has.

If you are still not persuaded, maybe you like to see just another abstract. Only in case that you're still doubting poor old Murphy:

"Comparison of intravenously administered methadone, morphine and heroin."
Jasinski, Donald R.; Preston, Kenzie L.
Drug and Alcohol Dependence 1986, 17(4), p.301

Abstract

To determine whether methadone is more potent in producing euphoria relative to its other opiate-like effects, single doses of i.v. administered methadone, morphine, heroin, and placebo were compared in nondependent postaddict volunteers. Morphine-like physiol., subjective and behavioral effects were measured periodically for 24 h after drug administration. Under the conditions of the expt. 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 3 compds. The relative potencies of methadone, morphine and heroin for the initial 5 h of effect were const. over all opiate-like effects, including measures of euphoria. Thus, methadone was not a selective euphoriant.

I think that should make further discussion redundant. Also, it directly confirms one of my previous statements, that is: Several opioids are INDEED comparable, concerning their psychoactive effects (this includes of course euphoria).

You said:

What other opioids/opiates do or do not do has no bearing AT ALL on any particular substance, only in terms of a class generalisation. A common opioid attribute IS euphoria but just as structure is not a universal facet, neither is a unified organic interation.

Sorry, but this is just wrong. It's not only simplified or something, it's wrong!
If the receptor-action profile and the rest of the pharmacokinetics of 2 substances are comparable, it is indeed correct to generalize. And as heroine, morphine and methadone (just to stick with these 3 examples) are indeed very similar in their overall action, it is only good scientific practise to draw analogies between those compounds. The last cited article only confirms this once more.


Just another argument against your point:

"Methadone maintenance treatment: the other side of the coin."
Ausubel D P
The International journal of the addictions 1983, 18(6), p.851

Abstract

The psychopharmacological rationale and clinical effectiveness of the methadone maintenance treatment program was subjected to critical theoretical and methodological analysis. It was concluded (1) that the MMTP constitutes and perpetuates an immature coping mechanism; i.e., "subliminal euphoria"--pervasive pharmacological shielding of addicts from the inevitable discomforts attending adaptation to the real world; (2) that it does not satisfy so-called tissue craving for florid euphoria because most "stabilized" clients actively seek and obtain same from heroin, methadone itself, and/or other potentially euphorogenic drugs; (3) that the source of this craving resides in the addict's personality rather than in his tissues; (4) that official evaluation studies of the MMTP grossly exaggerate its clinical effectiveness; and (5) that the MMTP has inadvertently created incomparably more primary methadone addicts than it has cured heroin addicts.

MAN! That's a study done with people withdrawing from other opioids with the presumable help of methadone. And look what the authors just found: Addicts seek actively methadone because it substitutes sufficiently for the desired effects, explicitly including euphoria. Only because that particular compound doesn't cause this in you...well, means nothing.

A last one, I won't respond anyway if the discussion is continued in an unobjective manner, as it was done before.

"Acute administration of buprenorphine in humans: partial agonist and blockade effects."
Journal of Pharmacology and Experimental Therapeutics 1995, 274(1), p.361

Abstract

Buprenorphine, a mixed opioid agonist-antagonist, is being investigated as a treatment for opioid dependence. This study compared the acute subjective and physiol. effects of sublingual buprenorphine to those of p.o. methadone over a wide range of doses and compared the ability of both drugs to alter the effects of an opioid challenge. Male inpatient volunteers (n = 9) with histories of opioid abuse participated in this double-blind, double-dummy study. Sublingual buprenorphine (0, 0.5, 2, 8, 16 and 32 mg) and p.o. methadone (3.75, 15 and 60 mg) were administered once weekly according to a Latin-square design, and subjects were monitored on a variety of physiol. and subjective measures. Twenty-four hours later, subjects were tested with ascending doses of i.m. hydrolater, subjects were tested with ascending doses of i.m. hydromorphone (0, 1 and 4 mg) given 45 min apart. Buprenorphine and methadone produced typical opioid agonist effects of long duration, including pupillary constriction, respiratory depression and elevations on subject-rated and observer-rated indexes of euphoria, sedation and opioid-like symptoms. The buprenorphine dose-effect curves were nonlinear and maximal effects for most physiol. and subjective measures were obsd. between 4 and 8 mg, with no greater effects obsd. at higher doses. The methadone dose-effect curves were linear across the range of doses tested. High doses of buprenorphine and methadone both attenuated the response to hydromorphone challenge 24 h later. These data indicate that there is a ceiling on the effects of buprenorphine in humans that may reduce its abuse liability and increase its safety, and indicate that opioid blockade occurs after acute administration of buprenorphine or methadone.

What shall I say? I'm correct I fear, until somebody posts the opposite and can proof his opinion, objectively!

End.

Murphy

 

[Jamshyd]

"You do not need a field trial because substances are field tested.": WHAT? Are you serious? It is called science. Subjectivity is completely worthless. What you, your mate, or 100 BLers is not going to overturn chemical improbabilities. Your supposition that the Rule is outdated is non-sensical because methadone is a comparatively old substance and is tried and true against it. Its euphoric properties were complete quantified before even my birth.

I must say I completely disagree with this statement.

If he, his mate, and 100 BLers (in methadon's reality, it is hundreds of thousands of people) find a substance euphoric to the point of going out and pursuing more while they aren't dependent on it, then it is the chemistry that is definitely wrong and needs to adjust itself to fit the reality that hundreds of thousands of people actively seek methadone for its euphoric properties. That is the process of science - to evolve in order to accommodate realities that contradicted it in the past.

I really don't mean to sound crude, rachamim, but have you considered the possibility that you may be unconsciously projecting on this thread a denial of the fact that some can enjoy euphoria from methadone, while you, due to your chronic use, would be never able to?

p.s. I have never tried Methadone even though it remains one of the ones most sought-after for me (but that is just for its purported NMDA-antagonism and my obsession with that).

 

[negrogesic]

I am sorry, but I must chime in here.

Methadone can certainly produce euphoria, especially when administered intravenously. In fact, the euphoria from a large size dose of IV methadone is quite profound, I know this from experience...

While it is also true that euphoria is not too prominent with commonly prescribed dosages of oral methadone in a tolerant individual, I believe this is largely dose dependent. I have taken up 780mg of methadone in single doses (massive tolerance, do not attempt!), and there is little question that these massive doses produced significant euphoria, followed promptly by profound sedation...

 

[fastandbulbous]

^ 780mg of methadone - fuck me that's enough to kill a whole football team of non-tolerant individuals! I know someone who was on maintainance of 170mg of methadone/day, but even he'd have doubts of that much in one go!

 

[negrogesic]

My MMT dose was 230mg/day, so I was only taking a bit more than 3x my normal dosage.

Strangely enough, it was actually pretty easy for me to quit the methadone. The benzos were a bit more painful...

Anyways, my point was that methadone can most certainly be euphoric. A massive dose of methadone is not entirely unlike levorphanol...

 

[Limpet_Chicken]

Rachimim, everything I have read, seems to say that the Mu1 isoform is the one responsible for euphoria and antinociception, Mu2 agonists produce more respiratory depression.

http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1427987&blobtype=pdf (meptazinol, mu1 selective agonist causes zero respiratory depression

http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1427987&blobtype=pdf Meptazinol is selective for Mu1 (mixed agonist/antagonist)

http://jpet.aspetjournals.org/cgi/content/abstract/228/2/414


Edit: just look at the wiki for propoxyphene/dextropropoxyphene which is selective to some degree for Mu2 agonism, and look how...nasty it is, and prone to respiratory depression.

I too, can testify to the fact that in opioid nondependent subjects, can certainly produce euphoria, no rush to it, but all day gouching, fun and games when I tried it, probably one of my favourite opioids, of the limited selection I have tried ( others being codeine, DHC, morphine, H, kratom, buprenorphine and a couple of others)

I prefer to think of the 'morphine rule' as more of a 'morphine general guide'
A rule can only be considered such, if nothing violates it, and with the thiambutenes and fentanyls, it was found not to hold true for all opioids.

Jamshyd, AFAIK the efficacy/affinity at NMDA is far, far lower than at MORs, chances are it would wipe you out many times over before you got to a level that would give dissociative effects, without a truly monstrous tolerance to opioids.

 

[fastandbulbous]

^ ^ Of that, I've no doubt as I had to take 10mg for phantom limb pain earlier this evening and am feeling quite at peace with myself. The euphoria from methadone seems to be more pronounced in the presence of pain

 

[Snowbear]

I experienced signifigant euphoria when I began using (40mg.) of Methadone daily for pain relief. Over a period of 60 days of daily use, the euphoria declined, but remained fairly strong throughout the 60 day period.

IMO the euphoria from oral Methadone was greater than the euphoria from oral Morphine. After reading what Mr. F & B said about "pain / euphoria", I recalled a recent episode of severe pain and I decided that the oral Morphine produced MUCH LESS euphoria than Methadone does during pain control.

IMO (unscientific) euphoria is the MOST SUBJECTIVE effect of opiates.

Does anyone besides Rachim doubt Methadone's ability to produce signifigant euphoria?

 

[Tchort]

This thread prompted me to finally get around to looking up potential metabolism-tweaking. So, Methadone is metabolised mainly by 3 enzymes: CYP3A4, CYP2B6 & CYP2D6. Inhibiting any one or any combination of these CYP450 substrates with another chemical will cause competition for the inhibited enzyme between Methadone and the other chemical. This would lead to higher serum levels of Methadone for a longer period of time- thus enhancing the sought after subjective physiological effects of Methadone (Euphoria, Sedation, etc).

Am I right so far?

Another means of potentiating the subjective physiological effects of Methadone would be the use of "Urinary Alkalinizers" (ex. Sodium Bicarbonate); as alkaline (higher pH) urine decreases Methadone excretion by kidneys (Source: Methadone Drug Interactions booklet). The lines I quoted in my last reply from this post

(

. . . 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)

. . .

Quote:
Gastric absorption was increased by alkalinization of stomach contents

)

So not only would consuming a "Urinary Alkalinizer" decrease Methadone secretion by the kidneys, they should also lessen the amount of time oral Methadone stays in the stomach by raising the pH of the stomach contents- thus reducing the amount of Methadone that would degrade in the stomach.

The list of CYP450 inhibitors is a long one, and so far I haven't found a single chemical that inhibits all 3 of the main enzymes that metabolise Methadone (CYP3A4, CYP2B6 & CYP2D6).

Theoretically, a combination of both the "Vickers Method" (Ginger) and a "Urinary Alkalinizer" should potentiate the subjective physiological effects of Methadone better than either on their own. Would the addition of one or more CYP450 Inhibitors (specifically strong inhibitors of CYP3A4, CYP2B6 & CYP2D6) further potentiate the Euphoria, Sedation, etc of Methadone?

I am not proposing anyone try this, it is simply for the sake of curiosity

Also, one of the most common and most widely known potentiators of Opioids is Grapefruit, whole fruit, juice or extract due to its alkaloids- which include the flavanoids (Naringin) and more importantly the furanocoumarins (Bergamottin & Dihydroxybergamottin). Yes the alkaloids present inhibit CYP450 enzymes, specifically CYP3A4; but also 'interfere' with (Inhibit) P-glycoprotein (Pgp).

Would it be stretching it to believe that inhibition of CYP3A4 plus inhibition of Pgp would lead to more potentiation than just inhibition of CYP3A4? Or would Pgp inhibition be negligible after the three CYP450 isoform enzymes that metabolise Methadone have been inhibited? (meaning, there wouldn't be a further positive effect realized by inhibiting Pgp in addition?)

Another question, I read this:

"The interaction caused by grapefruit compounds lasts for up to 24 hours and its effect is the greatest when the juice is ingested with the drug or up to 4 hours before the drug."

What about the timing of ingestion of these other substances? Would the Methadone and Ginger be consumed at the same time, or seperated by a time gap to achieve potentiation? If a "Urinary Alkalinizer" were consumed for this purpose, would it have to be consumed before the Methadone or taken at the same time, or some time after?

Same question with the CYP450 Inhibitors (for example Cimetidine, Goldenseal, etc), should they be consumed before the Methadone, or at the same time, or some time after? I have read conflicting reports (to take the Inhibitors an hour before, several hours before, at the same time, 30 minutes after and an hour after).

Two more quick, last questions:

SSRI's are listed as Methadone potentiators due to "Variable inhibition of CYP450 enzymes". I am confused as to whether this refers to daily administration of an SSRI, or would an individual who isn't taking them realize this potentiation from a single administration the way they would from other CYP450 enzyme Inhibitors?

And I haven't been able to find the exact metabolism of Omeprazole (Prilosec). Many sources report high incidents of theft of Prilosec pills for use with Methadone specifically:

Effects of Methadone Abuse Enhanced by Certain Pharmaceuticals

In April 2006 four individuals were arrested for shoplifting 12 boxes of Prilosec (Omeprazole) from a Queen Anne's County drugstore. Maryland drug task forces report an increase in thefts of Prilosec in Baltimore and Carroll County. Prilosec is believed to increase or intensify the high when taken in conjunction with methadone. Other drugs that are thought to intensify the effects of methadone include Goldenseal,a Tagamet (cimetidine), Antabuse (disulfiram), Prozac (fluoxetine), and Zoloft (sertraline). However, these drugs, when taken in conjunction with methadone, may cause methadone-related toxicity, such as oversedation, respiratory depression, or overdose.

Source: Maryland State Police.

Suspects steal large amount of heartburn medication
By Lamaur Stancil (Contact)
Sunday, December 23, 2007

SEBASTIAN — A recent attempt to steal a large amount of Prilosec from a local store is probably not the beginning of long-term heartburn for local police or pharmacies.

Nonetheless, Prilosec is one of the medications illegal drug users and manufacturers look to for enhancing their high. That could be why five people tried stealing more than 100 boxes of the over-the-counter heartburn pills from the Sebastian Wal-Mart on Thanksgiving weekend. Police spokesman said it was the second foiled attempt this year to steal a large quantity of the drug from the store.

The suspects in the November crime, caught before they left the property, didn't tell their motivations to the Sebastian Police Department. But according to the Department of Justice, Prilosec is believed to increase or intensify the high when taken with methadone.

A Maryland drug task force noted an increase in thefts of Prilosec in Baltimore last year, federal officials said. But locally, no law enforcement agency in Indian River County had a report of the drug being stolen prior to the Wal-Mart incident.

"Organized retail theft has been a growing concern," Walgreens corporate spokesman Michael Polzin said.

It became such a concern a few years ago that Sudafed — a cold medicine that illegal drug users highly coveted — was taken off the aisle shelves and placed behind the counters at many stores. However, Prilosec hasn't been enough of a frequent target for pharmacies to place the pills behind their counters, Polzin said.

Sebastian police apprehended three of the five suspects in the Nov. 25 shoplifting attempt. Yaitza Lopez Ramos, 23, of Orlando, and Oscar Armando Solorzano, 25, address unknown, posted bond while the third charged suspect, Jose Luis Soriano-Gutierrez, 25, address unknown,, remained at the Indian River County Jail as of Friday.

Police said the group took turns going into the store, grabbing several boxes of Prilosec at a time and filling an empty vacuum cleaner box in a shopping cart. The suspects managed to swipe 109 boxes from the shelves, worth more than $2,300. Their efforts were spotted by loss prevention officers, however.


http://www.tcpalm.com/news/2007/dec/23/suspects-steal-large-amount-of-heartburn/

 

[fastandbulbous]

Erythromycin is a CYP3A4 inhibitor which I'm taking for the minute for an infected sinus and the 10mg is lasting a hell of a lot longer than usual (took it at 3pm; it's now 9:30pm and it's still going strong)

 

[Hammilton]

May I ask what limb you're missing? My father in law is missing a finger of all things that continues to cause him great pain (not that I really care in his case!).

I was surprised it was allowed to continue unchallenged for so long that the mu2 subtype was responsible for euphoria, because it's the exact opposite (thank's Limpet).

The other thing that has still gone unchallenged was the idea that the Morphine Rule was what is required to have a euphoric opiate. It was never intended as such a thing; it was that thing that provided the basic pattern for what was required for a chemical to bind to the MOR.

I wouldn't say that it's outdated. Obviously it only applies to alkaloids, I don't think the discovery of herkinorin negates it at all. Is it not mostly accepted that it's binding to slightly different pocket of the receptor (it seemed mostly settled re: salvinorin a vs. pentazocine)? It seems to make sense.

Even the fentanyl's don't entirely break away from it, still has the tertiary nitrogen; Has a fentanyl with a quaternary carbon been synthed (on the piperidine ring).

 

[Limpet_Chicken]

I noticed that too, erythromycin potentiated codeine and morphine quite considerably, I can't remember off the top of my head wether it increased euphoria, or solely duration, but the duration was quit definately extended.

Although, breeding resistant bugs in vivo is not encouraged, so not a good idea to use an antibiotic regularly for that purpose (not directed at you, Fast, I know you know better )

Edit: Hammy, np, but I DID say something about the morphine rule being no hard and fast rule at all

 

[rachamim]

As I probably, said it is no spuprise that BLers will subjectively offer that they feel methadone offers "euphoria." Most, if not all posters are unaware that while it is a highly subjective subject, it is also a clinically identifiable pehnomenon. Using motiliy, twitch, and mapping euphoria is assigned a pseicif value system.


I have already explained about the Morphine Rule, as well as methadone being a conforming substance deficient in just one part of one of the individual axioms in the Rule, IT just happening to be the little aspect compeltly responsible for methadone's lack of or ability to produce euphoria.


To go further, I am sure most here are not even aware that the so called "rush" aspect associated with psychoatives is also a quantifiable value relating to BBB pentration (i.e. lipid soulbility as well as delivery)

I will ask anyone who is truly interested to research these points (if you are not able to research my earlier points) and find the truth for yourselves. I am sorry but offering a disputation based on your or your mates feelings is absolutely worthless. If it mattered at all I would simply offer my won which I have already related as diametrically opposed. What matters is actual scientific certainty and fact, not conjecture.

Now to begin responding to some points other than "Rush, Yes or No?"

TChort: Although your point is directed to the OP, as Fab asked him/her as well, "How would acidity or alkalinity effect discernible differences in absorption in the GI tract?" Actually Fast said it differently but that being the point (please do correct me if I am wrong Fast but after so many years here, Hive, etc. I know you you already know the answer and so paraphrased it in a more explicit way).


Jam: No offence but you are not thinking it through (talk about arrogant right?). See, IN COMPRISON to the plethora of accumulated sceitnfic work on this very subject, both the specific issues of methadone itself as well as euphoria, the subjective ramblings of 1000 BLers is not going to matter one iota.


IF euphoria was not a quantifiable value, its value being entirely subjective, the chemstry would STILL be relevant but not really worth arguing over because there then COULD be a mistake in the scientific thinking amonst the orthadox. However, it is not only quantifiable, it is already quantified in a myriad of ways.


If one perfoms brain scans (imaging either by itself or in conjunction with dyes), twitch evaluations, GI motilities, and even the all favorite sphincter reflex (haha) one already knows the real answer.


Most know the substance was developed during the Nazi Era (the very tail end) and as a widely consumed substance with half a century in existence, it is one of the most widely tested opioids (or even compared to opiates) with only codeine and morphine enjoying more attention.


"Many people seek methadone for its euphoric potential.": Well, what they seek it for is not an issue. What it has is. I know THAT seems like quibbling but truth be told, the majority of BLers (virtually all with perhaps 10 exceptions) could not explain the process of acetylation beyond what is represented in a half corked DEA Intel paper on SE Asia which was outdated when it was published almost 2.5 decades ago (original publishing date).


This is not denigration because it is not within BL's scope to try and attract people who would even really care about acetylation but my point in stating this is that a a person who cannot wrap their mind around a 101 subject like that is not even going to attempt to grasp the nuances I am trying to simply illustrate. Imagine 100 wanting to do so let alone doing it? NEVER.


Jam, no I am not projecting. I am not dealing in subjectives, not by others and certainly not by my own. IF I was, then I would be correct still! See, if the subjective expression of others is no more or no less valid than my own. You understand? As I said, this is physically definable, has been for decades, and is not a mystery hence the great number of specialist in methadone who...and I know this will be a shocker (haha)...claim methadone is non-euphoric.

Sure, one DOES see very intelligent people including researchers not specialising in methadone making the claim that methadone is euphoric but then even very able Forensic Chemists believe that "Tar" is simply "acetylated opium." I mean come on! It is enough to make someone get pains from laughing. Things get repeated so much and for so long by people not speciliasing in something that all of a sudden it has its own currency, cache and it is "common knowledge."


Luckily though, methadone as I said is one of the 3 most heavily studied opiates/opioids in existence and the one sentece references supplied on the subject by non-specialists is not even worth thinking about.


As for my "chronic use." I do not expect you to read every post I am throwing up in every forum, over the long course of my involvement on the site but on 7/20/07 I went Cold Turkey from methadone. When I came back to America in April this year I did renroll/reiniate because I expected an extended stay and the US' anal retentive concerning psychoatives,etc. I again W/D from the substance last month on my return home.

Even before 7/20/07 I had, over my 20/21 years on the substance had cause to W/D both CT AND otherwise several times for a variety of reasons and in a variety of differing circumstances. Ergo, who better to offer subjective ramblings if that is where we need to take it?

I have been on MMT on 2 continents, have a 2 decade long perspective with several abstentions for minimal periods of time allowing me to experience its initial stages in a variety of manners. I have also to date, actually used EVERY form of licit methadone commericaly released in the US, European nations, and most of Asia. I have also used two forms in S. America well 1 was a N. American brand, the other a Peruvian brand) so really, there is not going ot be much sense in examining it.

I will post this and then iniate anothe rpost to respond to other points, because this one is already getting a bit long.


(Edited for spelling)

 

[PsYcHoAcTiViSt]

Just my 2 cents but every time I have done Methadone it has given me PLENTY of euphoria. And as far as the sedating part.. well I like to get up and clean everything like i'm twacked out on some speed whenever i take done. Just cause I feel good.

 

[MurphyClox]

Just my 2 cents but every time I have done Methadone it has given me PLENTY of euphoria. And as far as the sedating part.. well I like to get up and clean everything like i'm twacked out on some speed whenever i take done. Just cause I feel good.

But hey - didn't you read it?!
As long as you don't perform a fully randomized double-blind, placebo-controlled study, your personal experiences are complete bullshit. Yours and the ones from I-dunno-how-many other Bluelighters who had the possibility to try methadone and get...well...'euphoric'. It's all placebo... There's this one guy who just doesn't get any euphoria from methadone - so you must be wrong!




...should I add a 'Sarcasm Ahoy!'-comment so that nobody blames me of flaming?

 

[rachamim]

Negro: Why be sorry? Glad to see you up and kicking after so long. OK, your points...


"The euphoria provided by a large IV injection is quite profound.": It has a rush but no euphoria Negro. IV as you certainly know is the most rapid onset after delivery. Woooosh, it washes over those partially or even completely starved receptors and voila! That is a rush, it is already quantified. Rush has a bit to do with a substance's composition and ALOT lot to do with Mu1, but more than anything it has to do with delivery.


This is why the most euphoric of conforming and non-conforming substances have absolutely no rush when delivered transdermally or intranasally. Who is going to argue that IV hydromorphone has no great "rush?" Certainly not me! Who will argue IV hydromorphone also has no great "euphoria?" Ditto!! But then take a dose in oral after compensating for the bio. differential so that the metabolised usage will be absolutely equivalent. This is something many people can see for themselves if they care to do a bit of exploration (providing they know what they are doing of course in terms of safety). Euphoria is there orally, but NO RUSH!!!



The thing about injectable methadone is that the rush while not great at all, is present and this suprises people who have only experienced oral formulations.

I know people dosing at 900 plus prescribed Negro and I myself was on 220 for most of the 2 decades (although last time it was 160). I have dosed at a bit over 1100 when fully acclimated and believe me, if there was a way to feel it, I would have been there. Availability in some countries has not been an issue for me, I am a well educated consumer and so there is nothing that would stymie me in that regard. To date, I have never felt it. Yet what I feel or do not feel is not important.


You can walk into a wall on it but that super-heavy sedation has no relation to euphoria.

Fast: I did a post I believe yesterday in OD talking about US dosing. Patients on Protease Inhibitors need to rectify the inhibtion and therefore are boosted quite a bit depending on the specific Inhibitor. I mentioned I do know a person on well over 900 daily, but at my last US clinic , which was actually up until last month (HUB I, Einstein College/Yeshiva, E138th Port Morris, South Bronx, NY) there were people regularly dosing into the 4 digits daily.

Of course this requires state authorisation and has only been possible over about the last 4 years. In NY they have to get the go ahead from the authority (OASAS) and it needs to accompany filed paperwork via plasma on relatively lower doses and when it begins climbing over 400 they require Trough Tests.


Still, some places like Florida still has a 100 mg. limit (daily), or at least people there tell me it has not changed. In Israel we have never had a limit that I remember.

Negro (Again): "Strangle enough it was easy for Negro to quit methadone, but alot harder for Benzos.": That is a no brainer Negro. Methadone is one of the easiest of moderate to heavy opioid/opiate substances in terms of the physical symptoms. It is the duration as well as the mental aspect that gets people wound up. Of course setting and mind set are EVERYTHING in this regard.

Benzo W/D can kill, as I amsure you know. It is much worse.


I documented my Cold Turkey beginning on 7/20/07 my Journal. The worst of it was two 15 minute bouts of leg twitching, 2 afternoons of localised lower back pain, ALOT of sweating (but I naturally sweat so it is not ALL attributable to the W/D), and of course the mental aspect which was terrible but I am well disciplined and 4 or 5 days into it was able to skin a cow and calf that had died in calving. It lasted a grand total of 8.5 days. It varies and can even take 14 days and counting for some unlucky people but the physcal portion does not vary in intensity. As they say: Methadone = little pain ALOT of waiting, Heroin/morphine = ALOT of pain little waiting.

The 2 or 3 days I had in Acute W/D from morphine in late autumn 2007 was hell on Earth.


(Edited for spelling)

 

[Hammilton]

I have already explained about the Morphine Rule, as well as methadone being a conforming substance deficient in just one part of one of the individual axioms in the Rule, IT just happening to be the little aspect compeltly responsible for methadone's lack of or ability to produce euphoria.

Do you know what the morphine rule is? It's not a rule that has anything to do with the effects of an opioid, it's a 'rule' that gives a general overview of what's needed for something to bind to the mu opioid receptor.

And methadone fulfills the morphine rule perfectly.

1. Tertiary Nitrogen
2. 2 Carbon linkage connecting to
3. Quaternary carbon
4. Phenyl group or isometric equivalent connecting directly to the quaternary carbon.

You can find this entirely in methadone's structure.

Structure and Euphoria aren't connected in that way. Structure determines binding (and affinity) and solubility. If a drug binds well, and is appropriately soluble (so it's able to get into the brain rapidly) and isn't destroyed too rapidly, it will produce euphoria. This applies to a whole lot of drug types.

If an agonist drug binds to a receptor that euphoria is a result of agonism, and it does this reasonably fastk, it's going to produce euphoria.

I'm willing to bet even modafinil would produce euphoria if it was absorbed faster (solublility is a major issue here).

And for someone who's insisting on having science, why are you ignoring all of the research that has been done and instead basing your claims on the fact that you haven't experienced euphoria from it?

You're not going to find even a single study or even quote that supports your idea that it's lacking some aspect of the morphine rule that causes euphoria or even that a specific aspect of the morphine rule is responsible for euphoria and not just binding. More than enough studies have been presented showing that methadone does indeed cause euphoria, but all you've presented is a misunderstanding of what the morphine rule is.

 

[fastandbulbous]

I noticed that too, erythromycin potentiated codeine and morphine quite considerably, I can't remember off the top of my head wether it increased euphoria, or solely duration, but the duration was quit definately extended.

Although, breeding resistant bugs in vivo is not encouraged, so not a good idea to use an antibiotic regularly for that purpose (not directed at you, Fast, I know you know better )

Edit: Hammy, np, but I DID say something about the morphine rule being no hard and fast rule at all

Yeah I wouldn't take any antibiotic unless it was to treat an infection of some sort, but if I've got to take it, it doesn't hurt to run a few home experiments on pharmacodynamics!

Actually, the most pronounced drug effect with erythromicin treatment is on ketamine - it doubles the length of action, but because it's mostly unmetabolized ketamine being excreted in the urinr & not norketamine, there's a lot less of the fuzzy, fucked up feeling afterwards (that's with 500mg of erythromicin 4 x daily)