Pharmacology - Opioid Tolerance: Reversing Receptor Sensitivity

[fiveleggedrat]

That was when he used. Swim did not use twice weekly months on end, but twice weekly every other 2, 3, or 4 weeks. Even after breaking for months, still there.

Can we please stop obsessing over Swim's tolerance? The point is, he's trying to fix it, and taking a few months off did nothing. He has the tolerance of a junkie for no reason.

Swim has a perma tolerance, and he's trying to reverse it chemically, since it won't revert on it's own over time. Simple as that.

[kimtp29]

Don't know if it's been mentioned. Swim is having the same problems for years. Does all this magic come from the same place where hormones are produced in the brain? Swim was told by Doc that there is something called hormone-binding. Where the glands? hold onto the feel-good chemicals in our glands? and actually hold them there and will not allow them to free. Will be running tests in a month to see if this is happening with swim. This may have something to do with something totally opposite maybe because swim can't get the energy from hormone shots that swim used to get. But am also pain patient and feel they is is all related?
Does the same feel good chemicals used in opiates come from the same place where the hormones are kept?
Still trying to do swim's own research as well.

kimtp29 added 48 Minutes and 29 Seconds later...

Fiveleggedrat:
Don't know how to edit post. Thanks for being a voice for swim as well. Same situation. swim is one of the chronic pain patients that ARE screwed for the same reason. Constant pain, used to get euphoria, euphoria sure as hell beats constant agony and depression from feeling like shit all the time. Does swim not deserve euphoria, but deserves constant pain and depression? Like swiy, don't know what went wrong. You are swim's voice. Never thought swim would find swiy.
What swim was talking about is hormone binding. Used to get the shot and get energy. So, same with hormone shots and opiates. What the fuck happened? SWim feels same way, pure fucking agony.
Swim's theory, hormone binding, won't release the feel goods, opiate binding, won't release the feel goods? Does this make sense, is it related?
Probably not related, but swim is feeling exactly like swiy and now doesn't feel alone.
Swim will be following you, in hope for better quality of life.
Swim's regime, fentanyl and oxycodone. Though it was the best anyone could get.

Reputation Comments on this post:

	Good ideas from this post. Thanks!
	thanks for this informative post

[fiveleggedrat]

It's a similar process, yes, some part of the brain goes out of wack and starts over/under compensating for something

But dude, thanks for the thought, Swim just found some bomb info looking stuff on hormones, that goes back to my earlier CCK theory:

peptide- Cholecystokinin- CCK- duodenum
-

Release of digestive enzymes from pancreas Release of bile from gallbladder hunger suppressant

CCK is a hormone. If you havent been keeping up, CCK:

evidence has suggested that it also plays a major role in inducing drug tolerance to opioids like morphine and heroin, and is partly implicated in experiences of pain hypersensitivity during opioid withdrawal

SO! What that means is Swim has either A) Receptor Inversion or B) High CCK levels that are not dissipating.

Read this:

Secretion of CCK by the duodenal and intestinal mucosa is stimulated by fat- or protein-rich chyme entering the duodenum

That means CCK relates to a high fat or high protein diet; Swim currently has a VERY fat high diet at the time, which he did not in the past; Could a bad diet relate to opioid tolerance?! It's possible from this, at least in theory.

Swim has been having stomach pains/problems/over acidic stomach since he moved and tolerance began.

CCK administration causes nausea and anxiety

Well, that answers why Swim has had nausea problems and anxiety problems ever since this opioid thing began. Yes, not direct CCK admin, but it still has SOME reasoning behind it.

CCK also causes the increased production of hepatic bile

Coincidence? Maybe. Now, possible treatments?

gastrointestinal system

• Somatostatin suppresses the release of gastrointestinal hormones
  • Cholecystokinin (CCK)
  • etc etc etc!

So somatostatin would supress release of CCK, as well as others (who cares about those now )

After a bit of looking, somatostatin is not really something that looks easy to get. Alternative? The similar synthetic, Octreotide aka brand name Sandostatin, which is prescription only, and the few that sell it require a prescription.

Well, that's out the window

Oh, what's this? Website, you can get Swim a 0.05MG/ML vial of Octreotide generic from Pakistan? Go for it buddy! (Pending completion!)

Hm. That's one theory that can be put to the test, if all goes well.

I mentioned this in the Useless Chatter thread, but Swim went to/called most rehab centers/Methadone centers/etc in the Orlando area, asking about naloxone, and if they distribute/prescribe it. None knew what naloxone was, and none could help at all.

Seems that either another solution or a trip to California to get it are in order.

Edit: Damn dude, if Swiy is on Fent and Oxy and still getting nothing, Swiy is in a bad spot. Swim can down morphine like full on heroin addict now and get nothing.

Hopefully, my research will help Swiy too! Check back, this is my main project, and I research this daily.

Reputation Comments on this post:

nice argment--can see you've been reading up on the endocrine system. Unfortantely, I Iwant to bieleve, but thnk you sh...

[Richard_smoker]

Some clinical researchers tried CCK & Octreotide. Be carefull with your money and health because taking a the drugs during a pill or tablet, the drug will release all of itself, all of the sudden.

Now, for some reason, this doesn't work with CCK.

Supposedly, there are some investigations underway trying to use CCK for weight loss.. WHY? MD's feel that GNC stuff is all crap

and who can blame them?? everything is treated with drugs...herbal 'shit' is never the same quality twice. and health food stores have little to no expertise. They're mission is sell product--whether it's effective or not.

Normally, if you took a dose of CCK (without time-release), the pill will quickly dissolve in your stomach, then immediately absorbed by the duodenum (1st part of small bowel). unfortunately, this does not do much or anything to help you lose weight...

Soooo... a unnamed crazy mad scientist has been experimenting with his own perfect diet pill. CCK has been tweaked and several different 'blinds' to weigh particants time-release mechanism.

CCK needs to work its way through intestines for dietary effect. Take it in the currenty-available form (, and it still be a dissolving pill in your duodenum--ensuring that you won't be hungry.

WHY IS THIS SO?? WHY DON'T THEY JUST MAKE AN 'XR' PRODUCT LIKE ADDERALL??

simple. money. MANY of today's western civilization might get high, escape, or self-medicate with drugs. But the problem with CCK is that NO ONE will make money from it.

BEWARE: Big pharma woud bend over backwards, it they could discover a SYNTHETIC / slightly different for CCK or . So be on the lookout for a "newer, better, non-jittery way to curb appetite.

-DICK

[VoodooFeather]

This whole thread is very interesting & would LOVE for someone to actually figure out a way to successfully reverse the tolerance effect.

I assume the country stopping all the progress is the USA.

Maybe a bunch of Intelligent/Commonsensical Group of people could form a small army and create our own nation, and call it Petoria in Rhode Island.

But seriously this research has to be done. For pleasure, or at least for saving lives.

[fiveleggedrat]

I have not been able to find ploglumide anywhere, Swim has definately looked for it and Swim's well aware about it, but thanks for mentioning it!

Anyone have any other CCK antagonists that aren't impossible to get?

fiveleggedrat added 289 Minutes and 5 Seconds later...

Edit: I found my old EMT friend who, a year ago, offered naloxone to Swim before he knew what it was; hopefully he is still a EMT, but even if not, he knows tons of med people and people who can get special things (medical insiders)

Sweet, sweet. I called him tonight and I'm going to go see him tomorrow. If Swim gets the Naloxone tomorrow, he'll test that theory out the same day.

Oooh, Swim's so excited! The unreachable is in reach!

Wish Swim luck!!

Swim has long ago decided if he reverses opioid tolerance and can Enjoy them again, he will do some projects for DF as payback for all the help here, as well as throw a party for him and a few friends

[fiveleggedrat]

New test: Swim read in http://www3.interscience.wiley.com/j...TRY=1&SRETRY=0 and a few other papers that mu tolerance can be reversed through K antagonism, and now Swim's going to attempt some salvia and see how that goes, with a mu agonist test tomorrow.

[fiveleggedrat]

So the Salvia theory failed the test.

Swim smoked salvia a few times the other day to see if it helped tolerance, Since Swim read some info that it might.

Swim ate 350mg tramadol and 12mg rectal hydromorphone to see if Swim could get anything from combining them; Swim got a nice, dreamy state (still no euphoria but got some minor eye fluttering, if Swiy know what I mean). After Swim dosed, he sat down in bed and zoned out, almost nodding but more dream-like, as morphine type drugs tend to be.

The high was over about 1 hour into the whole thing. CNS sedation and miosis remain, as well as histimine release and insomnia.

Jeeze. 4mg used to have Swim euphorically nodding for hours.

Swim's hoping to get naloxone soon and try that test out, still confident on it. Swim also needs to get octreotide and proglumide.

[Matt The Funk]

Originally Posted by fiveleggedrat

So the Salvia theory failed the test.

Swim smoked salvia a few times the other day to see if it helped tolerance, Since Swim read some info that it might.

Swim ate 350mg tramadol and 12mg rectal hydromorphone to see if Swim could get anything from combining them; Swim got a nice, dreamy state (still no euphoria but got some minor eye fluttering, if Swiy know what I mean). After Swim dosed, he sat down in bed and zoned out, almost nodding but more dream-like, as morphine type drugs tend to be.

The high was over about 1 hour into the whole thing. CNS sedation and miosis remain, as well as histimine release and insomnia.

Jeeze. 4mg used to have Swim euphorically nodding for hours.

Swim's hoping to get naloxone soon and try that test out, still confident on it. Swim also needs to get octreotide and proglumide.

The effects you described are similar to the ones I have. It's all the effects, for the most part, without the euphoria. Thanks for all the self-research! I think SWIY should try to take a small break before attempting again, to make sure tolerance is completely gone.

[kimtp29]

5LR,
With the naxolene and others, does SWIY just need to take the pill 1 time, or is this a treatment that takes weeks? or days?
Also, did betsym PM swiy any info that would help Swim with swim's chronic pain? Or can betsym PM swim the same info that would help swim?
Swim only gets 2 10/325 percocets daily to help with breakthrough, down from the 3 in recent months. How does swim get doc to give more breakthough?, b/c obviously others have the same pain and get more. Doc says anything over 2 a day won't work. This can't be true! Perc's aren't that great, but are better than nothing.

[MarkyMayhem]

Originally Posted by kimtp29

5LR,
With the naxolene and others, does SWIY just need to take the pill 1 time, or is this a treatment that takes weeks? or days?
Also, did betsym PM swiy any info that would help Swim with swim's chronic pain? Or can betsym PM swim the same info that would help swim?
Swim only gets 2 10/325 percocets daily to help with breakthrough, down from the 3 in recent months. How does swim get doc to give more breakthough?, b/c obviously others have the same pain and get more. Doc says anything over 2 a day won't work. This can't be true! Perc's aren't that great, but are better than nothing.

If no one has said it DO NOT take naloxone or any other opiate antagonist if you take opiates daily! It will cause precipitated withdrawals, and buddy - they are BAD!!!!

re: your doctor. Opiates can be titrated up indefinatly. You can look it up in any number of sources online if you want to print it out and show it to him, it's a widely known and documents medical fact.

I suggest he just doesn't want to be responsible for you having a raging pill/opiate addiction. I say bravo. Look up opiate pain syndrome. Sometimes[most times] high dosage long term opiate usage end up with the patient still in pain and with a huge habit besides.

-m

[kimtp29]

What is the alternative to upping your meds? What would one recommend, otherwise? Swim didn't ask for the accident, the pain, or the meds. Swim went to the doctor and was told to take this and that. Swim was in swim's 30 when this started and did not know about medicines being addictive, much less that they were called opiates. Swim has learned alot. Swim has never been around drugs or opiates, so swim was a little naive. Swim tried pot once in teens, hated it---so didn't want to mess with anything that would make you high. Maybe cocaine and others are great, but swim won't mess with them.
Swim might be addicted physically, but not emotionally. Docs can take this medicine away anyday, as long as they can come up with something to control the pain. Won't even bat an eye---will try anything.
If swiy's not in chronic pain, swiy's had no idea what it's like. Man, swim wishes this on noone.

[duhduhduhda]

swim has a similiar problem with tolerance
4 mgs intranasal hydromorphone used to fuck him up

but now he has to iv 3 at a time its pretty depressing going to the needle helped out alot in the beginning cut his doses in half but tolerance climbs even faster then any other ROA
he's been using heroin cuz its cheaper than 9 dilaudids a day at the rate he's going he'll be on intervention within the next year

but until then he'll watch this thread

[fiveleggedrat]

Yeah, 4mg used to be like BOOM!

6mg IM injection is like "Huh? Did I just do a drug, cause I sure can't feel it!" Same thing for 16mg rectal, done the right way too.

How often does Swiy use? Swim uses once or twice a month, if lucky. If not, he ends up going 1, sometimes 2 months with nothing. Breaking does not help, either.

[stupidorange]

Definitely subscribing to this thread! I have had some luck with potentiators, but a reversal of tolerance... ah, that'd be something!

[imyourlittlebare]

getting naloxone in any form is hard. a friend of swim is doing a thesis on music therapy and opiate receptors and cant get a dr to help with it. Swim offered but, swim told this person that it can cause depression and anxiety. swim dont know why places dont offer it. Anyways. The whole idea that opiate addiction can be taken care of by nmda receptor antagonist or naloxone is false. They tried several things. If taking opiates and you are on certain nmda receptor antagonists you can prevent tolerance or addiction depending on the subtypes. Addiction with opiates is just a very interesting thing. Swim wishes research would be done more on ibogaine because the way it works is very interesting and it has to do with increasing certain proteins in certain areas of the brain and specific changes. Swim has never come across anything indicating that naloxone or anything else will decrease tolerace because of the changes that occur in certain neurotransmitter transporters and proteins. Thats my take. Although the GABA-A receptor is very unique but thats because rather than xanax binding to the receptor and mimicing gaba, it increases gaba-s action. Where as morphine rapes your receptor and makes changes molecularly that swim just doesnt think that tolerance can be reversed because the action is so different. Swim wrote on the run. Will elaborate later!!

imyourlittlebare added 1 Minutes and 23 Seconds later...

also, tolerance comes back quickly. although you lose it when your off and thats why alot of heroin addicts die, it comes back very quickly. swim has found that once you use a certain level it stays at that level and it wont go back. but swim is clean now thank everything. His life isnt total shit although he hates clonazepam and buprenorpine

[fiveleggedrat]

This tolerance occured from weekly use of tramadol and monthly use of hydromorphone, all orally.

[cra$h]

wow, that's some true determination kid. But I think swim's in the same boat. after a 3-4 month break, 15mg of hydrocodone, nothing. Just the slightest hint of euphoria, even with tums and shit. Swim's still young with opiates, and never really needed more than 30-40mg, mostly because of rediculous prices. But for getting completely bombed at 30mg, then nothing at 1/2 that makes no sense. At first I thought it could just be a psychological tolerance, which could be swiFLR's situation, but now I'm thinking it could be something much deeper. I think I'll help out a little on this research, see what we can all come up with. With a couple people constantly conglomerating, we'll triple production rate!

[Richard_smoker]

i think there are a few factors of tolerance, habituation, and reward 'sensation' that are eluding much of this discussion.

There is something as-yet-unexplained about exactly what goes into the make-up of a 'perfect' experience. One thing that hasn't been mentioned at all--but is extremely important in my opinion--is the unpredicatable nature of exactly HOW HIGH one feels on a particular dose given certain constants (like time since last dose, how many milligrams of such and such compared to so and so feeling).

Psychologists proved years ago that the way to create the MOST addictive patterns in rats was by using randomly-administered rewards. For example, you can train a rat to press a lever in order to receive a treat (food, drug, dopamine, electrical stimulation of the brain's pleasure centers). If you want to see a rat go ape-shit on the lever, pressing it like a homocidal maniac, then you only give the reward randomly (like a slot machine). For example, you only give the rat one treat for every 30 lever-presses (on average).

When I say that there must be something similar going on with the world's most highly addictive drugs (heroin, hydrocodone, etc.), this is more than just theoretical conjecture.

There seems to be a great deal of evidence that these disappointing experiences with opiates are 'part of the game itself.' Although you might not realize it's happening to you, these negative experiences factor into your future opiate consumption-decision-making in a very powerful way.

Cra$h, can you honestly say that after taking the 15mg of hydrocodone and being disappointed, that you're LESS LIKELY to keep trying this drug out in various doses, searching for the elusive euphoria?

-DICK

[fiveleggedrat]

But where's the dosage increase stop? What's the point where one can say "Something's up..."

Swim's trying to get hydrocodone, about 150mg, and he will taking comparative doses. Swim honestly expects to be able to down 80mg with only minimal effects.

Swim's also getting some kratom extracts, the most convincing, concentrated doses of alkaloids. One should be around 200mg mitraygynine (yes I spelled that wrong.) per 7grams material, and doses of that alkaloid range, from reading, around 10-70mg, so Swim should be able to get something decent, at least, from 100mg, as well as the other alkaloids present in the mixture.

Swim really wants to get heroin again to see how things go with a powerful agonist that can be IV or IM.

[cra$h]

Originally Posted by Richard_smoker

Cra$h, can you honestly say that after taking the 15mg of hydrocodone and being disappointed, that you're LESS LIKELY to keep trying this drug out in various doses, searching for the elusive euphoria?

-DICK

oh, of course swim's going to toy around with hydrocodone much more. He was just a little pissed because he didn't even feel a buzz. But what swim was thinkin would be if you could reverse the receptors by increasing sensitivity, swim could just make the opioid receptors extremely sensetive, possibly to the point swim's bombed off a mg or 2 (wishful thinking) and possibly could help in sober emotions, helping swim stay happier. But swim's just hypothesising now, and much research needs to be done, but I figgured the more imput, the more questions are solved, speeding up the research process.

Reputation Comments on this post:

refreshing to see an actual, honest answer to an apparently annoying supposition. thanks for not bullshitting us.

[Ilsa]

suboxone consists of buprenorphine and naloxone, so there's swiy's naloxone...swim takes it (8 mg) a couple times during the week and can still feel 120-180 mgs of morphine on weekends. it def has worked for swim in preventing tolerance. swiy may have already tried this but swim thought she'd throw it out there.

[Richard_smoker]

yeah, analgesia is how doctors measure pain in the NON-OPIATE-ADDICTED PATIENT!

that's the kicker. if you're addicted to the high, then you will require an escalating dose, irregardless of how much analgesia you're getting from the drug. kinda makes sense though because if you're an addict, you don't care about pain-killing properties. you care about the euphoria.

pseudo-addiction is basically where the analgesic tolerance goes up. this is normal, but it generally takes a while to develop. when it does develop, it is quickly erradicated by increasing the dose once. this is compared to "addiction" for which you can NEVER increase the dose enough for satisfaction. it just won't ever happen. -DICK

[fiveleggedrat]

What would Swim be? He has psychological hunger for opioids, like his other favorite drugs, but he does have no issues with use. He has no withdrawal symptoms, but experiences tolerance equal to that of an addict of a serious nature, but even they get euphoria than Swim.

[Richard_smoker]

well, you're a damn 5-legged rat, of course! haha -DICK

-seriously, i've told you this before and i really don't feel like my experience-based opinion is being given much credibility. i think swiy're pushing the envelope. not because of ANYTHING about you or anything wrong with you or your decisions. i think you know exactly what i'm saying because even YOU said that even addicts get more euphoria. that's the missing link. start taking the shit everyday and swiy will begin to feel a little like shit everytime swiy starts to go too long without opiates. I think it is the DRASTIC difference between this shitty baseline feeling just prior to dosing---compared with the euphoria swiy WILL GET from the opiates... this will begin to define the 'level of euphoria brought on by opiates.'

now you see why i call it 'playing with fire?' it's a very difficult concept to explain to someone who doesn't realize what physical addiction actually feels like. and i can only imagine how insulting this information must seem for someone to read about himself. but it has nothing to do with you and everything to do with swim's experience with the exact same experience you describe.

unfortunately there's never going to be ANY GOING BACK to the mind-blowing experiences of swiyour first few times. the only way to get what you're looking for is to just let oneself slip into the addiction for about a week. that should be long enough. -DICK

Reputation Comments on this post:

	Exactly right. Good advice too. #71
	the truth