Heroin Why is methadone withdrawal far worse than heroin withdrawal?

[Zopiclone bandit]

I was the medicine cabinet man, and would provide quality info, with my fee being a cut of course.

I am starting to really like you, fuck knows why I never noticed you before but I can relate to you 100% & that is a rare thing.
Yeah, all the medicine cabinet men need a little cut for their service, you always give a small tip to the Waiting staff, waiters / waitresses when going out for a Meal.

 

[agoraphobe]

I'm going to admit something. I only use Kratom, Ativan and gabapentin. Not daily, but I cycle everything.

I've been thinking about hanging outside the methadone clinic near me and seeing if someone would sell me some exiting. I don't know why I'm thinking these things.

 

[KurtAurelius]

I'm going to admit something. I only use Kratom, Ativan and gabapentin. Not daily, but I cycle everything.

I've been thinking about hanging outside the methadone clinic near me and seeing if someone would sell me some exiting. I don't know why I'm thinking these things.

I’ve thought the same but there’s no way to even know how to get that conversation going, or for it to end up leading to a mugging.

 

[Dr. John Thackery]

I've been thinking about hanging outside the methadone clinic near me and seeing if someone would sell me some exiting. I don't know why I'm thinking these things.

i’ve always thought of doing that. i get methadone for pain so my entire monthly supply as pain patient with zero history of addiction on my record is the daily dosage given to a homeless fentanyl and crack addict pissing dirty everyday

apparently the withdrawl pain of a convicted rapist and violent criminal on drugs that is a leech on the system while i pay the taxes to fund his methadone and ambulance rides; is more valid than my health related pain i didn’t ask for.

anyways.

not sure if you can get methadone in this way but i’ve heard of ppl scoring everything else in methadone clinic lines

 

[Dr. John Thackery]

"We do not seem to have learnt anything from the experience of our American brethren … cannot our legislators understand that our only hope of stamping out the drug addict is through the doctors, that legislation above the doctors’ heads is likely to prove our undoing and that we can no more stamp out addiction by prohibition than we can stamp out insanity?"

100% TRUTH, reading that link right now.
Thanks for that, the most Logical issue to the Opiate issue is to give us people who are sick "medicine" which we need.

I have worked fucking HARD Manual labour jobs before on a big Smack habit, I can swing a Pick-axe or sledge hammer with the best of 'em in a field under the peak mid-afternoon Sun as long as I am not sick, I could work like a normal person & pay Tax etc if I had "Medicine" but The State wanna give me a sick note & put me on Benefits for the rest of my Life as I am a Junkie, it's fucking insanity, the solution is simple & clear.

the buerracracy in place to deal with disability is a massively wasteful tax theft scam. same for homelessness. same for addiction. same for crime. these institutions all have the financial interest of worsening the problem they exist to fix.

the ppl running it making 700,000 USD or more a year are social workers whey a Bacherlors degree from a garbage school. they are making more than surgeons from top medical schools or scientists at top pharma companies curing disease. for a job that almost anyone could do; but it’s the government so the goal is stealing from taxpayers and firing an overpaid under qualified 85 year old beurrocrat to hire a 27 year old harvard social work graduate that is more up to date on modern research and could do a way better job will never happen. these dinosaurs die at their desk at 90 while the last ten years of their work was dementia ridden waste.

ppl in need of help could be helped at a small fraction of the cost if it wasn’t a criminal racket. and also the criminal racket incentivizes crippling and keeping alive as many suffering corpses as possible to justify the bureaucracy that steals about 95% of the funding going into it and barley helping the ppl that need help.

 

[vision conquest]

As mentioned methadone is very potent and has a long half life.

Chronic use wise at doses equivalent to 300mg morphine or more then methadone ends up being 6x - 20x more potent than morphine and it builds up in the liver and fatty cells, so it slowly releases out of them, causing full blown withdrawal that lasts around 4 weeks and Post-Acute Withdrawal Syndrome (PAWS) that lasts months to years depending on how long you've been using and if you've weaned off or went cold turkey!

If you have the spare cash once you get sorted make sure you have a stash to fall back on in case you ever screw up your script again or are very ill and can't pick it up.

There's sites that will supply kratom in/to the UK and apparently have had zero problems with dried leaf material.

Any strong full agonist you're not gonna take whilst bored is good back-up.

I've been on methadone for over 26 years now...this is a good idea and something I always try to have...of coarse the trick is being able to have it and not hook in to it.

I like to always have a bunch of 100mg morphine tabs on hand and this tactic has saved me some pain on more than one occasion over the years.
I'm currently on a dose pretty close to yours @Zopiclone bandit and on the times when for whatever reason I've had to go without my dose 300mg of morphine taken orally will keep me from suffering for a day.

I agree that the long half life of methadone which makes withdrawl so protracted is what makes it so dam hard to kick.

I have a couple of plans in the works for when I taper down low enough to attempt to jump.

1. stockpile enough morph tabs to switch from a low dose of methadone onto morphine for about two months then jump from the morphine.

2. SR17018...I have heard a lot of anecdotal stories of success with this compound which I'm currently trying to source.
I hope you're feeling a bit better man.

 

[thurston]

Who the hell first made Methadone in the first place?

Nazis, seriously.

Methadone - Wikipedia

en.wikipedia.org

 

[thurston]

His one of my Idols of all time.

Have you seen this?

 

[Zopiclone bandit]

Have you seen this?

Yes I have, I also have the single 12" Burroughs's did with Kurt Cobain.

 

[ChemicallyEnhanced]

They are in the "Very Wrong" camp.

lol I been there before.

Why the ever loving fuck would they do that to you? Forcing someone to suddenly cold turkey from strong opioids like that is tantamount to torture IMO.
How are you doing now?

 

[Ddeeee]

Haven't taken methadone for nearly 2 years now I am considering getting some and taking tiny tiny doses to help me jump off my habit but yeah methadone is very very bad it makes you ten times more lazy to the point where you sleep all day and are just wasting away your gonna end up (ime) feeling suicidal because it takes all your motivation and energy away.

You know its bad when a 0,8 of tt raw wont even make you feel 100 percent well unless you have taken atleast 20-25 percent of your daily methadone dose, thats what it was like for me, having 2 addictions.

When i finally got off methadone I felt like a new person I had lots more energy, motivation and my tolerance dropped so much it was mad, Only problems were I was still on gear(but after being on methadone I dont give a fuck) and I put on lots of weight which took ages to lose.

DO NOT take methadone if you are not 100 percent serious about it your tolerance will hit the roof. That being said I am sure if I was serious about cleaning up, when I got on the juice and took it as the gp prescribed I would have got clean or atleast got off the smack. But I was just not willing to do that, and my penalty was months of pain when I fell out with my keyworker who was talking to me like i was an idiot, and told them fuck their methadone I will 'just quit it' hahaha I wasnt feeling so high and mighty within a week of that conversation let me tell you..

that being said everyone is different and maybe methadone just ain't for me. I am considering trying suboxone soon. take care people.

 

[Skorpio]

"No, fentanyl is not a Serotonin-Norepinephrine Reuptake Inhibitor (SNRI).
Fentanyl is a high-potency, synthetic opioid analgesic that works primarily by binding to mu-opioid receptors in the central nervous system to relieve pain."

Why is Fent made out to be so bad to get off if it isn't in the SNRI family?
I seen videos of people in Fent withdrawl & they looked like me yesterday, people so sick they are on the floor unable to move their legs vomiting their guts out but Fent isn't one of those fucking evil SNRI things, how bad is Fent withdrawl to methadone?

A few reasons. One is that fentanyl is very lipid soluble, and it accumulates in our cell membranes and fat. This makes it last longer and metabolize slower. A more real life example of this is how fentanyl patches will keep dosing you for a bit after removed as the fentanyl deposits in your fat, and then slowly moves into systemic circulation.
(Anybody who is interested in following this deeper can read this open access paper)

Second, agonists at the mu opioid receptor (and likely most other G protein coupled receptors) tend to activate the receptor in multiple different ways. Fentanyl activates a signaling pathway that builds tolerance more quickly (and provides more respiratory depression per unit of euphoria) than other opioids such as morphine-type opiates. This results in fentanyl addiction progressing more rapidly, and to a point of more severity than with morphine type opiates. This is likely even a touch of an oversimplification, as this paper (open access) notes, different agonists tend to produce fairly unique responses at the same receptor, leading to different functional responses).

 

[Allylbenzene]

Second, agonists at the mu opioid receptor

There's a third also, TLR4 activation. Naltrexone is the most well-known TLR4 antagonist which is partly what makes it helpful for opioid cessation.

...increased evidence indicates that neuroimmune system, especially Toll-like receptor 4 (TLR4) signaling, plays an important role in the different stages of drug addiction. Drugs like opioids, psychostimulants, and alcohol activate TLR4 signaling and enhance the proinflammatory response, which is associated with drug reward-related behaviors. 10.1007/164_2022_586

 

[Skorpio]

There's a third also, TLR4 activation. Naltrexone is the most well-known TLR4 antagonist which is partly what makes it helpful for a variety of purposes.

I’m not quite sure what you mean by this.

Are you saying that fentanyl exhibits biased agonism/functional selectivity at toll like receptor 4 as a causal driver of worse withdrawals?

Or that fentanyl is a stronger tlr4 agonist than other opioids?

I would love to see a paper that compares the tlr4 affinity (and efficacy) of various, class-representative opioids.

 

[Allylbenzene]

I’m not quite sure what you mean by this.
Are you saying that fentanyl exhibits biased agonism/functional selectivity at toll like receptor 4 as a causal driver of worse withdrawals?

Or that fentanyl is a stronger tlr4 agonist than other opioids?

Apologies for the missing context. Fentanyl's TLR4 activity is likely a significant contributor to it's tolerance & habituation ability and it's general harmful effects. Pro-TLR4 drugs cause hyperalgesia making opioids a poor option for long-term pain relief.

Opioid receptor agonists non-stereoselectively activate the TLR4 signaling pathway
— 10.3389/fimmu.2020.01455

...structurally diverse opioids (including the clinically relevant agonists morphine, fentanyl, remifentanil, methadone, oxycodone, buprenorphine, meperidine and antagonists naloxone and naltrexone) interact with TLR4
— 10.1177/0310057X211063891

Drugs like opioids, alcohol and psychostimulants activate TLR4 signaling and subsequently induce proinflammatory responses, which in turn contributes to the development of drug addiction.
— 10.3389/fphar.2020.603445

Indeed a comparison between their TLR4 activity would be interesting. It's possible that methadone engages TLR4 in a "more harmful manner" than heroin.

According to the present DATA, methadone affects the TLR4 expression. It may however cause adverse consequences by increasing the TLR4 expression. Therefore, the useful analgesic properties of methadone should be separated from the unwanted TLR4-mediated side effects.
— 10.4103/abr.abr_97_21

 

[Allylbenzene]

Why is methadone withdrawal far worse than heroin withdrawal?

It looks like methadone promotes MS-type conditions while T3 (thyroid hormone) reverses the MS-type condition:

Interestingly, we observed that the co-incubation with the pro-myelinating hormones T3 and T4 leads to a three-fold increase in the MBP+ population in methadone-treated oligodendrocytes, suggesting that methadone-induced impairments could potentially be reversed by stimulating alternative salvage pathways. This finding suggests that co-therapies accompanying opioid replacement therapy could be beneficial in normalizing the reduced myelination observed after methadone exposure.
— 10.1038/s41598-024-67860-7

Maybe this partly explains why methadone causes bad withdrawals (or generally negative effects). This means that methadone requires it's own specific harm reduction strategy...

 

[Skorpio]

10-4

Also in addition to directly activating tlr4, opioids, through mu receptor agonism cause the production of high mobility group box 1 proteins which are on there own agonists of tlr4.

Frontiers | Toll-Like Receptor 4 (TLR4)/Opioid Receptor Pathway Crosstalk and Impact on Opioid Analgesia, Immune Function, and Gastrointestinal Motility

TLR4 recognizes exogenous pathogen-associated molecular patterns (PAMPs) and endogenous danger-associated molecular patterns (DAMPs) and initiates the innate...

www.frontiersin.org

Though both pathways should be blocked by tlr4 antagonists.

 

[Allylbenzene]

Though both pathways should be blocked by tlr4 antagonists.

Add an antihistamine to that also (or a mast-cell stabiliser) as it seems that histamine up-regulates TLR4, opioids being well-known for their pro-histamine effects.

The OTC palmitoylethanolamide reduces histamine and TLR4, sounds like a cheap harm reduction option for methadone users.

 

[Zopiclone bandit]

This results in fentanyl addiction progressing more rapidly, and to a point of more severity than with morphine type opiates.

My God, now I get why people in The USA on Skidrow, L.A. were on the floor unable to move & puking their guts out.

. This is likely even a touch of an oversimplification

I can only speak for myself here BUT I feel many others on BL will agree with this post.
Many of us on here have a very basic education in terms of Science & Chemistry, I sure wouldn't make a real-life Breaking Bad "cook" shall we say & I am not alone here.

Yeah I have done very obscure RC's but that was just reading the mg dose on Erowid, TR's on here for the RC then eating it, just because a man has done 3C-E (Escaline) & 4-MeO-PCP as a small example doesn't mean I know anything about how stuff works, all I know is 4-HO-MET is amazing to trip on for example

Keeping things simple helps way more people than a BL member doing a post that has Atomic Mass info, the Coordination Number of a compound, Enantiomers etc.......

It took me ages on Google reading about why I had such a HORRIFIC Trip from DXM & this is the text I had to work through, to me most of this may as well be in Chinese.

"The enzyme primarily responsible for breaking down (metabolizing) dextromethorphan (DXM) in the liver is cytochrome P450 2D6, commonly known as CYP2D6. [1, 2]
A deficiency or absence of this enzyme leads to a condition known as being a "poor metabolizer" of DXM. [1, 2]

Key Facts About CYP2D6 and DXM

• Function: CYP2D6 converts DXM into its active metabolite, dextrorphan (DXO), through a process called O-demethylation.
• Poor Metabolizers: Approximately 5% to 10% of the Caucasian population has little or no functional CYP2D6 enzyme activity."

 

[benjyman.]

Seriously if you been on methadone for any amount of time you really should taper as the protracted withdrawal and paws causes so many to relapse it ain't funny.

Agmatine really helps with the tapper, I currently dropping 10% every couple of weeks using Agmatine and a few helpers..

Looking at sr17018 for that final push , or maybe just a water drop, keep the sr just for emergency

Best of luck