ULDN - The magic weapon to reduce and keep tolerance to Opioids low

[snmfmy]

Eventually I found an MD that would do it though. They're generally not big on alternative methods that actually work.

Interesting, because the first time that I was made aware of low dose naltrexone was by my physician.

 

[Juicewrldfan]

So would a full dose of it as in regular dose used in opioid maintenance help reverse tolerance if taken for 6 months?

 

[Hexenstahl]

So would a full dose of it as in regular dose used in opioid maintenance help reverse tolerance if taken for 6 months?

???
Who told you that about 6 months? That's nonsense. If you're clean from opioids and take a 50mg NTX pill and wait 5 days your tolerance will be near zero. You'll actually feel euphoria again but we all know how that ends. You'll be back at your old dose in like a week and the cycle starts anew...

 

[Foreigner]

Interesting, because the first time that I was made aware of low dose naltrexone was by my physician.

Things have changed a lot in the past five years. It has become more mainstream. I have several friends using LDN now. Sometimes I can't even get my prescription refilled on time because the pharmacy is out of naltrexone!

 

[Pharmanaut]

Can someone with knowledge in pharmacology please explain why naloxone is unable to sensitize the opioid receptors as opposed to naltrexone? As far as I know they bind to the same receptors and have the same mode of action, right? Why then is naltrexone so incredibly effective in μ-opioid receptor sensitization? Is it because of the long duration? Help would be much appreciated.

Apologies for leaping in years later but you piqued my interest & I did a little research as to why naltrexone but not naloxone.
I've been reading that whilst Naloxone & naltrexone are both competitive antagonists with a greater affinity for the receptors than their natural agonists like morphine. They bind quicker & tighter stopping the natural agonists from reaching the receptor.
(Agonists bind and cause the receptor to send a message down onto the cell causing a cascade of events leading to a pharmacological response.
Antagonists bind but do not trigger the receptor to send the message.)
Naloxone is metabolised quickly & in about an hour it has vacated the receptors. Job done, OD reversed, breathing response restarted.
But naltrexone has a slower, more complicated action. Naltrexone has a much, much longer half-life, it's effects on the receptors can last 24 hours. But it has a nifty trick up it's sleeve...
While the metabolites from the breakdown products of Naloxone are not psychoactive, there's a metabolite from naltrexone that is! It's called 6β-naltrexol & it's an agonist itself. So as some receptors become vacant over it's 24 hours of action there's 6β-naltrexol floating about to bind, trigger & stimulate the release of our endogenous endorphins giving rise to euphoria at the μ receptors & elevating mood, causing analgesia & reward at the k receptors ect.
So I'm thinking it's action isn't really lowering tolerance, it's acting as an internal, baseline, 24 hour, CNS wide, plush, deep pile carpet like substrate on which your lower dose natural agonist can build.
I'm no psychopharmacologist, no training or education, totally self-taught so I could be wrong here. But it's what it looks like to me.
One interesting side point I read & VERY nervously tried is that if you take a Suboxone tablet, dissolve, wheel filter & partake the bupe is faster to the receptors than the Naloxone & binds to the μ receptors so tightly it blockades the Naloxone from kicking it off!
First time, it's a very strange feeling knowing what's floating around your bloodstream with a pokey bupe rush at the same time! One molecule from disaster!

I've been enjoying your posts, good to meet you meine neue freundin der stahlzauberin.
Tschüß

 

[jambabomba]

I think I need to clarify a few things here: I never claimed that this is a magic bullet, much less prevents addiction (the opposite actually). As I have wrote on the previous page the effects are somewhat unpredictable and if anything this "trick" worsens an opioid addiction because you have a more or less reliable reset button. This time for example I used it again and it worked. With euphoria coming back on "command", my addiction has turned into something that is truly a perennial, lifelong millstone around my neck. All hope for achieving a clean life has been destroyed. And those three days of forced abstinence for the naltrexone to do its job on my receptors feels awful because I have to put myself into a semi-comatous state with high doses of benzos to prevent the cravings from ruining the reset procedure. Or k-holing myself for the entire time, barely eating anything and being aware of anything until those three days are over. This is just how bad opioid cravings have become for me since my naltrexone experiment. I used to be able to abstain from opioids every once in a while for entire months. Now I have to substitute every day that I don't have opioids with all kinds of drugs in order to not run amok and lose my sanity. Life has turned into a countdown where I count weeks and days, switch this drug for that drug just to distract myself from the craving of another drug.

I miss the times where I just smoked an occasional joint, while playing PS2 with my sis back in the early 2000s. Life was so simple. The problem isn't the drugs (antiquity had an abundance of Opium but no records of an opioid "epidemic"), it's the shitty postmodern society that turns life into such a horrible, empty experience, that people have the need to take drugs to feel better. That is so fucked up! Destroy the community, create dysfunctional families, cut the emotional bonds between people and put them into this ridiculous invention that we call "city" where everyone is alienated from everyone, topped up with an ultra-competitive dog-eat-dog mentality, creating general mistrust among people, divide and conquer through social engineering and make them perpetually exhausted and mentally stressed by giving them a heavy dose of existential uncertainty, and boom, people wonder why drug addiction exists.
"Brain disease" my fucking ass! Drug addiction is the soul's expression to escape from a fucked up, dysfunctional society and not because "muh rewiring of da brain and neuroplastic changes bla bla look at my elite university credentials, dats da proof dat my words are true...believe da science you stupid sheep".

Sorry for the off-topic rant, but I just had one of the worst days of my life (someone very dear and close to me just died) and I just needed to vent off some of that anger and despair. My aggression isn't directed at anyone here (I apologize if that appears to be so; my communication style might appear rugged sometimes but I'm a gentle, sensitive and kind being at heart), but I just needed to get it off my chest.
I won't be responding to PMs and comments for a while after making this post. I need some time off. Time off the internet, time off work, people and everything. I'll be going to my vacation home near Grindelwald in Switzerland and remain there in seclusion for a few weeks to get my mind sorted out and mentally/emotionally regenerate myself. Maybe this is a good time to reprioritize some of the things in my life.


Ok back to topic:


NO! You don't use LDN when dependent on opioids. That WILL send you into precipitated wd and it's the most horrible body-splatter-gore-torture-experience-from-hell that you can possibly imagine. You start with dosing around 5µg (we're talking about 0.005mg here!!!) and gradually up 5µg from there in incremental doses. And most importantly: never ever go above 100µg! If ULDN has been unsucessful for you then just stop there. Trust me you don't wanna go into precipitated wd. There is absolutely nothing to stop the torture (except calling the ambulance and let them put you in a coma for the entire duration, but depending on the tolerance you might be thrashing on the ground with so much physical/mental pain that you can't even call anyone. It is best to experiment with such things while someone is present). Aside from the bodily pain (and the life threatening water loss), your mind will be traumatized by the experience. It is nothing like a normal cold turkey where it gradually builds up and then goes back down again. You experience everything at once at peak wd level at maximum intensity for several days.

You are greatly exaggerating the precipitated withdrawals. It is not like that. It is not on/off digital thing but it is more like analog signal where the effect is dependent on the amount ingested. I have several times took over 0,75mg of naltrexone with my current addiction to tramadol (400-500mg daily + 30-50mg oxycontin daily) and even that amount gives only mild withdrawals for couple of hours. And it is actually very nice to induce those mild withdrawals some days for few hours as then you get new high from doses that did not previously gave it anymore. The more you suffer the more you reduce your tolerance - no pain no gain. So it is only good to induce those withdrawals few times a week or even daily with naltrexone. Just limit the time you induce those withdrawals for few hours. The amount needed to induce withdrawals for only couple of hours can be easily found by increasing the amount of naltrexone ingested everyday until you start to notice withdrawals.

But on the other hand, if you increase the naltrexone slowly by only 5ug increments what will most propably happen is that you just free yourself from addiction and some day just notice that your opioid doses do not work anymore and you don't feel much difference whether you eat them or not so basically at this point you can stop eating opioids and do not feel much anything. It happened to me when I reached naltrexone dose of around 0,75mg. Then my opioids did not work and I did not feel much any withdrawals either if I did not take my normal doses.

If you take 50mg suddenly then it might give withdrawals that will last few days but not with 1,5mg or 0,75mg. I take now quite regularly 0,35-0,75mg of naltrexone by night. I started straight from doses of 200-300ug or 0,2-0,3mg. That dose might give first mild withdrawals. 100ug might also give if your addiction is severe. Even less are needed the more severe your addiction is.

By day I take my opioids and if I take close to 0,75mg then the opioids will not work next day but only very, very mildly. By the evening or next day they gradually start to work again. But no bad withdrawals. Sometimes I take too much and then I am next day in semi withdrawal state but what this naltrexone actually does is _prevents_ withdrawals and frees you from addiction if you slowly increase the dosage. Those milligram doses actually make withdrawals less.

There is great variation though and I have quite slowly build my tolerance to higher doses of naltrexone because now when I start to reduce my naltrexone dose I can taper simultaneously my opioid doses and they will be working more effectively.

 

[jambabomba]

You are greatly exaggerating the precipitated withdrawals. It is not like that. It is not on/off digital thing but it is more like analog signal where the effect is dependent on the amount ingested. I have several times took over 0,75mg of naltrexone with my current addiction to tramadol (400-500mg daily + 30-50mg oxycontin daily) and even that amount gives only mild withdrawals for couple of hours. And it is actually very nice to induce those mild withdrawals some days for few hours as then you get new high from doses that did not previously gave it anymore. The more you suffer the more you reduce your tolerance - no pain no gain. So it is only good to induce those withdrawals few times a week or even daily with naltrexone. Just limit the time you induce those withdrawals for few hours. The amount needed to induce withdrawals for only couple of hours can be easily found by increasing the amount of naltrexone ingested everyday until you start to notice withdrawals.

But on the other hand, if you increase the naltrexone slowly by only 5ug increments what will most propably happen is that you just free yourself from addiction and some day just notice that your opioid doses do not work anymore and you don't feel much difference whether you eat them or not so basically at this point you can stop eating opioids and do not feel much anything. It happened to me when I reached naltrexone dose of around 0,75mg. Then my opioids did not work and I did not feel much any withdrawals either if I did not take my normal doses.

If you take 50mg suddenly then it might give withdrawals that will last few days but not with 1,5mg or 0,75mg. I take now quite regularly 0,35-0,75mg of naltrexone by night. I started straight from doses of 200-300ug or 0,2-0,3mg. That dose might give first mild withdrawals. 100ug might also give if your addiction is severe. Even less are needed the more severe your addiction is.

By day I take my opioids and if I take close to 0,75mg then the opioids will not work next day but only very, very mildly. By the evening or next day they gradually start to work again. But no bad withdrawals. Sometimes I take too much and then I am next day in semi withdrawal state but what this naltrexone actually does is _prevents_ withdrawals and frees you from addiction if you slowly increase the dosage. Those milligram doses actually make withdrawals less.

There is great variation though and I have quite slowly build my tolerance to higher doses of naltrexone because now when I start to reduce my naltrexone dose I can taper simultaneously my opioid doses and they will be working more effectively.

I am actually planning to start a trial with this 0,75mg dose so to see if body actually develops tolerance to that and reaches some kind of equicalibrium where opioid receptors become actually so upregulated that those opioids start to work again despite of that naltrexone dose.

I fear that it might not happen though, because of naltrexone's high affinitet and my previous experiences have told me that even 1,5mg will build up in the body enough to prevent opioids for making you high. But maybe it could be worth trying to increase dosage of naltrexone even higher for little longer time periods - up to 50mg per day while simultaneously being addicted to tramadol (400-500mg day) and oxycontin (30-50mg day) if that would make the difference.

What I speculate might happen is that at some point you become just indifferent to opioids and because you do not notice their effects anymore you stop reinforcing your mind and slowly teach yourself that opioids are not worth eating. But this is psychologically difficult. Even though I know this will work, and you can free yourself from addiction without noticing basically much anything, your ego does not accept it. Because you know that by simply reducing the amount of one pill you can feel the effects of the other pill again.. that is the difficult part in this game.

 

[jambabomba]

Apologies for leaping in years later but you piqued my interest & I did a little research as to why naltrexone but not naloxone.
I've been reading that whilst Naloxone & naltrexone are both competitive antagonists with a greater affinity for the receptors than their natural agonists like morphine. They bind quicker & tighter stopping the natural agonists from reaching the receptor.
(Agonists bind and cause the receptor to send a message down onto the cell causing a cascade of events leading to a pharmacological response.
Antagonists bind but do not trigger the receptor to send the message.)
Naloxone is metabolised quickly & in about an hour it has vacated the receptors. Job done, OD reversed, breathing response restarted.
But naltrexone has a slower, more complicated action. Naltrexone has a much, much longer half-life, it's effects on the receptors can last 24 hours. But it has a nifty trick up it's sleeve...
While the metabolites from the breakdown products of Naloxone are not psychoactive, there's a metabolite from naltrexone that is! It's called 6β-naltrexol & it's an agonist itself. So as some receptors become vacant over it's 24 hours of action there's 6β-naltrexol floating about to bind, trigger & stimulate the release of our endogenous endorphins giving rise to euphoria at the μ receptors & elevating mood, causing analgesia & reward at the k receptors ect.
So I'm thinking it's action isn't really lowering tolerance, it's acting as an internal, baseline, 24 hour, CNS wide, plush, deep pile carpet like substrate on which your lower dose natural agonist can build.
I'm no psychopharmacologist, no training or education, totally self-taught so I could be wrong here. But it's what it looks like to me.
One interesting side point I read & VERY nervously tried is that if you take a Suboxone tablet, dissolve, wheel filter & partake the bupe is faster to the receptors than the Naloxone & binds to the μ receptors so tightly it blockades the Naloxone from kicking it off!
First time, it's a very strange feeling knowing what's floating around your bloodstream with a pokey bupe rush at the same time! One molecule from disaster!

I've been enjoying your posts, good to meet you meine neue freundin der stahlzauberin.
Tschüß

You have understood it wrongly. It does rise levels of endorphins but not because 6b-naltrexol is agonist but on the contrary because it is antagonist. Also naltrexone may be weak partial agonist but on the presence of MOR agonist it becomes inverse agonist and upregulates receptors it then occupies. So I guess it behaves like that in the presence of endorphins too. In any case, it is the antagonism (or inverse agonism actually) that is most likely the helpful thing here and that which raises endorphin levels (which can be up to 300% with only 3mg dose) and upregulates/sensitizes receptor/opioid system in general.

How else would you explain opioid supersensitivity after high dose naltrexone treatment is stopped? Or immense high even from couple of beers? If you eat few months naltrexone like 50-100mg/d and then stop it and 1-2 week later try a 10mg oxycontin even that could then be lethal or at least you could be nodding. And sixpack of beer will give you a high like in youth. Your opioid system has become hyper sensitive to any agonists - including endogenous agonists - which would be very unlikely if the naltrexone would have all a long just increased endogenous agonists which would have just desentisized the system down and increased tolerance to other agonists too.

Remember that ex. Beta-endorphin is 10-100 times more potent/has higher binding affinity than even heroin. So increasing only endorphins without blocking simultaneously MOR or acting as inverse agonist towards them will definitely downregulate and desentize your opioid receptors to both endogenous and exogenous opioids too.

So if it only increases endorphins without simultaneously blocking MOR then you would not feel a sixpack of beer after naltrexone is stopped like you did in your youth and you wouldn't be on the edge of dying from normal opioid dose.. But both are true after stopping naltrexone.

 

[CRICKETBEE]

Wanted to post some updates. I am now up to around 30-35 drops a day. I can sense a noticeable shift in my general mood (endorphin??) levels. Honestly I do not remember the last time I experienced intense chemical euphoria from a drug but that has become a common feeling for me lately. (it also makes me wonder if a regiment of ULDN would have any effect on bringing some of the magic back to MDMA use?)

Even my regular (very low) methadone dose of 25mgs (which I now wait to drink until after my daily ULDN) caused feelings of warmth and good feeling this morning! I have a feeling that whatever I decide to do ULDN or VLDN will remain part of my daily regiment from now on.

 

[Hexenstahl]

Wanted to post some updates. I am now up to around 30-35 drops a day. I can sense a noticeable shift in my general mood (endorphin??) levels. Honestly I do not remember the last time I experienced intense chemical euphoria from a drug but that has become a common feeling for me lately. (it also makes me wonder if a regiment of ULDN would have any effect on bringing some of the magic back to MDMA use?)

Even my regular (very low) methadone dose of 25mgs (which I now wait to drink until after my daily ULDN) caused feelings of warmth and good feeling this morning! I have a feeling that whatever I decide to do ULDN or VLDN will remain part of my daily regiment from now on.

Finally someone else here who has made positive experiences with ULDN. This will give NTX more credibility for this kind of use. It's truly a wonder drug...

 

[bcc23]

Finally someone else here who has made positive experiences with ULDN. This will give NTX more credibility for this kind of use. It's truly a wonder drug...

unfortunately i havent gotten it to work for me. ive kept a log of effects for the following (approximate) doses

.0625ug - no difference in opiate effects
.125ug - no difference
.156ug - no difference
.1875ug - no difference
.25ug - no difference
.3125ug - no difference
.375ug - no difference / maybe slightly weaker
.4375ug - no difference / maybe slightly weaker
.625ug - weaker
1.25ug - weaker

at this point not sure what ntx dose to try next

 

[Hexenstahl]

unfortunately i havent gotten it to work for me. ive kept a log of effects for the following (approximate) doses

.0625ug - no difference in opiate effects
.125ug - no difference
.156ug - no difference
.1875ug - no difference
.25ug - no difference
.3125ug - no difference
.375ug - no difference / maybe slightly weaker
.4375ug - no difference / maybe slightly weaker
.625ug - weaker
1.25ug - weaker

at this point not sure what ntx dose to try next

You have only tried ULDN in nanogram doses. The highest dose you took was 1.25µg. From this point on I would increase up to 100µg or until you start to notice slight wd symptoms. My sweet spot is 33µg as I have mentioned elsewhere and most people on reddit seem to take anywhere between 1µg and 20µg. If really nothing ends up working you might be a non-responder, similar to how some people don't feel anything from opioids, no matter which agonist they take and how much. Don't make like 10µg jumps. You might accidentally skip the dose that works. Increase in 3µg increments. 30µg didn't work for me and if I had increased by like 7µg or so, then I would have never discovered that 33µg does wonders for me. I hope it ends up working for you. If you really end up being a non-responder then I recommend you take 60mg of DXM before you take opioids. It is known to boost opioids (not euphoria unfortunately, but at least sedation). Better than nothing I guess.

P.S.: in case you're wondering why I'm recommending you to go higher even though with 1.25µg you started noticing weaker effects, here is the reason in case you missed my explanation of the pharmacodynamics of ULDN: this compound doesn't follow typical bell-shaped curve dose patterns. Instead you might get equally good results with 120ng, 1.5µg, 90µg, but everything inbetween won't work for some odd reason. The hormetic dose to provoke the Filamin A protein class into modifying MOR is quite erratic which explains the highly idiosyncratic dosage pattern. As long as you don't experience withdrawals, going up might eventually end up giving the results you're looking for.

 

[bcc23]

You have only tried ULDN in nanogram doses. The highest dose you took was 1.25µg. From this point on I would increase up to 100µg or until you start to notice slight wd symptoms. My sweet spot is 33µg as I have mentioned elsewhere and most people on reddit seem to take anywhere between 1µg and 20µg. If really nothing ends up working you might be a non-responder, similar to how some people don't feel anything from opioids, no matter which agonist they take and how much. Don't make like 10µg jumps. You might accidentally skip the dose that works. Increase in 3µg increments. 30µg didn't work for me and if I had increased by like 7µg or so, then I would have never discovered that 33µg does wonders for me. I hope it ends up working for you. If you really end up being a non-responder then I recommend you take 60mg of DXM before you take opioids. It is known to boost opioids (not euphoria unfortunately, but at least sedation). Better than nothing I guess.

P.S.: in case you're wondering why I'm recommending you to go higher even though with 1.25µg you started noticing weaker effects, here is the reason in case you missed my explanation of the pharmacodynamics of ULDN: this compound doesn't follow typical bell-shaped curve dose patterns. Instead you might get equally good results with 120ng, 1.5µg, 90µg, but everything inbetween won't work for some odd reason. The hormetic dose to provoke the Filamin A protein class into modifying MOR is quite erratic which explains the highly idiosyncratic dosage pattern. As long as you don't experience withdrawals, going up might eventually end up giving the results you're looking for.

will give it a shot, thanks

 

[CRICKETBEE]

For BCC23 I thought I would post a link to an interesting redditt discussion about ULDN.There are some comments from a person named serpentWorship where they talk about Nanogram and EVEN picogram ranges! not sure if anyone here has tried these ranges at all.

 

[Hexenstahl]

Wow that's an awesome post you found there. He is also on LM just like me, which means he is either german or finnish. Gonna read the discussion when I'm back home. Thank you!


That comment of his is especially enlightening:

"My dear opiophiles, I finally solved the issue. Today I took a ULDN dose that is high (450ng) relative to my sweet spot (100ng) and it works now. How did I find out what to do to solve my little problem? Well, yesterday I started researching a bit about the neuropharmacology of ULDN and found a white paper that explains what ULDN actually does in the brain and when I read that document, a light bulb suddenly lit up in my head and I knew exactly why my old dose stopped working through inductive reasoning.

So here is a short explanation of what actually happens when you take ULDN: naltrexone in these low dosages doesn't actually bind to µOR as most people erroneously believe, but it actually binds (and very strongly so) to a class of regulatory proteins called "Filamin A" which is responsible for a process that in neurology known as "signal transduction". It basically modulates the binding preference of µOR. This Filamin A has essentially two binding sites: one high affinity site which becomes active when taking a low ULDN dose (keep in mind that "low dose" is highly idiosyncratic when it comes to ULDN) and a low affinity site that becomes active when taking a high ULDN dose. ULDN does its job regardless of which one of these sites is activated, but you wanna make sure that it binds to the high affinity (low dose) site as it's going to do its job much more effectively and efficiently than when it binds to the low affinity (high dose) site.

You're probably wondering now what the heck all of this nerdy talk has to do with my dose not working anymore. Well, it's quite simple. You see, when I took those 100ng it was apparently considered a low dose by my brain, and so it bound to the high affinity site, but I seem to belong to a subgroup of ULDN users who have Filamin A binding sites that very quickly become desensitized upon repeated binding to the high affinity site, which translates to a diminishing rate of return when successively using the same low dose. So I thought why not alternate between a low dose and a high dose to bind in a rotating manner to those two binding sites, in order to prevent either one of them becoming desensitized. And well, it works! The 100ng is my sweet spot which does its job in the most potent way when it comes to tolerance reduction and potentiation/prolongation of the opioid high, but the 450ng does essentially the same, only with weaker results, so I'm going to switch back and forth between 100ng and 450ng every day to make ULDN work consistently.

I hope this helps those few people out there who don't belong to the fortunate majority who can just take the same ULDN dose everyday and struggle with the same issue as I did and have therefore given up on it because they probably thought that ULDN doesn't work for them or that it's placebo or something. Folks, it DOES work, you just have to rotate between high and low affinity dosing. It's a real shame that ULDN isn't more extensively researched, otherwise this would have been known. Feel free to ask any questions if you have them. I'm here to help!"

It seems he was unable to maintain the effectiveness of ULDN once he found his sweet spot and later found out that he simply needs to rotate doses. Never heard of this phenomenon but it's good to know for those few people who experience the same issue.

 

[bcc23]

as an update, I was finally able to get some results from uldn. here are the doses i have tried so far which had results

8.75ug - stronger sedation, weaker euphoria
7.5ug - noticeably stronger effects (particularly sedation)
6.25ug - slightly stronger effects

unfortunately it doesnt seem to boost euphoria much, which aligns with what some other users have mentioned, but could still be a useful tool. i will probably try a few more days at around 7.5ug since that is where i got the best effects

 

[tryptakid]

as an update, I was finally able to get some results from uldn. here are the doses i have tried so far which had results

8.75ug - stronger sedation, weaker euphoria
7.5ug - noticeably stronger effects (particularly sedation)
6.25ug - slightly stronger effects

unfortunately it doesnt seem to boost euphoria much, which aligns with what some other users have mentioned, but could still be a useful tool. i will probably try a few more days at around 7.5ug since that is where i got the best effects

I've appreciated this thread, and following your journey throughout - thank you for contributing to this and keeping us updated. As a former heroin addict and lifelong drug nerd, I find this discussion particularly fascinating. It seems that the euphoria boosting you mentioned may only be achieved by precipitating withdrawal through a full dose, waiting for a couple of days, and then using the drug you're hoping to get a desired effect from. Perhaps at that point you could restart your ULDN regimen to maintain a more favorable tolerance profile, taking into account the wisdom in this thread, as well as the linked comment from reddit mentioning switching between higher ULDN and lower ULDN doses. Obviously, so much of this remains unknown, but the beauty of this forum is that these posts are available for as long as we have a means to access them. I think about that quite often, how precious such a thing is. What a time to be alive.

Best of luck to you

 

[Tetrapharmakos]

Further update:
the receptor reset seems to be somewhat unreliable, but not in terms of tolerance reduction (this will always happen when doing ULDN), but in terms of euphoria. For those who haven't followed this thread: back in January I accidentally found out that a normal naltrexone dose (50mg) brings back the honeymoon phase of opioids. I repeated the same procedure last sunday (of course after I tapered off), waited 72h and then took heroin again expecting that I will experience euphoria again. Unfortunately that didn't happen. I was fully sedated but I felt none of that warm, fuzzy, rose colored glasses feeling, which was extremely disappointing. So either I have done something wrong, or this method is somewhat unreliable. I will repeat the same procedure next month and report back.

I was looking up studies on Naltrexone recently-

One 50mg pill dosage of naltrexone was found to block opiates to a fair degree for 72-108 hours. I think you need to either reduce your naltrexone dosage, or wait a bit longer. I can find the specific study if you are interested

 

[Tetrapharmakos]

I have been noticing the same thing. But I use only small dose codeine (90mg) to test my responses. I think the half-life of metabolite 6b-naltexol is so long (12) and the receptor affinity is so strong that you will really need to abstain longer time periods to get receptor site cleans. In the studies they even say that naltrexone occupies receptors even after 7 days after the dose and undoes the effects of opioids despite its apparent short halflife.

In my case, I have not used any opioids in many months but instead have been using LDN 3-6mg at evening. I used 6mg of naltexone 48h before I took 90mg of codeine and I did not felt anything. 6b-naltrexol should have been <0,5mg at time point 48h but apparently accumulated amount + that was enough to prevent effects. So I think naltrexone even at low milligram doses really occupies receptors for many days and needs a quite strong opioid to counteract that effect at least within 48h time window within its use. If you used 50mg naltrexone you still had about 3mg of it left at 48h time point and in studies they have noted it will act against opioids even past 100h timepoint. So that might explain you did not get full effects as I did not get none effects with milder opiate and lower dose of naltrexone.

I think if using mg amounts of naltrexone one needs to wait at minimum 4-7 days before getting full agonism from opioids or use strong opioids with affinity at least on same level as naltrexone which would mean at least strength of morphine.

Edit: But in my case there has to be considered also enzyme interactions which might have affected the metabolism of codeine. As I have been using many herbal products like curcuma, piperine, ashwagandha and bacopa. And some of them like piperine are enzyme inhibitors but at least I am not aware of any strong CYP2D6 inhibitor in my use so I think main reason for lack of effects is naltrexone.

Edit2: OK, it seems piperine can inhibit also CYP2D6 so maybe it can reduce the effects. Does anyone have experience with piperine and codeine?

It is very important to note that the "elimination half-life" of naltrexone and its metabolites from the body is actually *shorter* than naltrexone a duration of action in opioid receptors.

From Wikipedia (Sources can be found on the Naltrexone Wikipedia page):

"In a study of the duration of MOR blockade with naltrexone, the drug with a single 50 mg dose showed 91% blockade of brain [11C]carfentanil (a selective MOR ligand) binding at 48 hours (2 days), 80% blockade at 72 hours (3 days), 46% blockade at 120 hours (5 days), and 30% blockade at 168 hours (7 days).[9][10] The half-time of brain MOR blockade by naltrexone in this study was 72 to 108 hours (3.0 to 4.5 days).

The half-life of occupancy of the brain MOR and duration of clinical effect of naltrexone are much longer than suggested by its plasma elimination half-life.[9][88][10][89] A single 50 mg oral dose of naltrexone has been found to block brain MORs and opioid effects for at least 48 to 72 hours.[88][10][90] The half-time of brain MOR blockade by naltrexone (72–108 hours) is much longer than the fast plasma clearance component of naltrexone and 6β-naltrexol (~4–12 hours) but was reported to correspond well to the longer terminal phase of plasma naltrexone clearance (96 hours).[9][10][48] As an alternative possibility, the prolonged brain MOR occupancy by opioid antagonists like naltrexone and nalmefene may be due to slow dissociation from MORs consequent to their very high MOR affinity (<1.0 nM)."

Naltrexone elimination half-life is apparently only 4 hours. It's metabolite 6β-Naltrexol is said to have an elimination half-life of 13 hours, however:

"6β-Naltrexol is said to have very limited capacity to cross the blood–brain barrier."

 

[Jnowhere]

It is sad, I remember, because I was there when Hexenstahl said she was never coming back to Bluelight, ( It had absolutely nothing to due with me, she was mad about her posts being deleted)