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

[Hexenstahl]

How does one legally control a ligand that if administered alone has no activity?

The legislative normally handles such things by creating the legal fiction that the possessor of one of these ligands also has the other ligand and intends to administer them both, which gives government the pretext to regulate the substance in question accordingly. It is the same principle that is used on drug/explosives precursors. The government simply assumes that you intend to manufacture something like a C4 landmine when they catch you possessing conc. H2SO4. They don't care that it is a million times more likely that I am actually using sulphuric acid to drop the pH of my fruit mash down to 2.8 - 3.3 (trust me, it's extremely economical to do it this way), because the fiction says that conc. H2SO4 is used by non-licensed, private persons for something illegal and nefarious.

For those who are unaware: the word "fiction" in law is not to be confused with fiction as it is used in our everyday, non-legal language. The latter describes something imaginary, the former however is a non-rebuttable presumption that is either affirmative or disaffirmative of falsehood. It was invented to create useful concepts such as legal persons (corporations), but unfortunately it can and is often abused by our governments to create absurd realities that you can't even rebut in court.

 

[vima]

Now I'm even more confused. Your body is reacting in such an erratic way to NTX. Withdrawals while having no NTX in your system?! I think at this point the scientists over at the LDN research trust might be immensely interested in you as a test subject lol. They have the knowledge and the means to actually conduct research on you. A frankenstein neurobiology such as yours could give us tremendous insight into how (U)LDN and opioids interact with one another.

right??? seems super weird; i truly don't get it. and shit, if you can make the intros, i'd love to talk to those scientists.

P.S.: if they end up asking you to sign a waiver, pls turn around by 180° and LEAVE. If they end up asking you to sign a waiver and don't even offer you compensation for potential damages, pls turn around by 180° and leave even faster. The medical industry only ever asks you to sign waivers if the responsible parties have knowledge of the odds being stacked against you to an overwhelming degree. Even if they do not end up asking you to sign a waiver, you can very easily test how honest the responsible parties really are with you when they say that it's "totally safe", simply by giving them a notice of liability. If they still wanna do "business" with you, then that's a sign that they are actually certain about the safety of their procedures. If however they end up rescinding their offer...well, I don't think I need to explain why they would do that.

If you ever end up being asked to partake in a study, send me a PM and I'll write you a notice of liability (free of charge ofc).

also, LOL!! thank you very much for the sincere offer of support, and your description was really funny.

gosh, i love this site. i can't believe i lurked for so many years before posting. it sure is a whole new worlllldddd *insert aladdin song*

 

[4DQSAR]

@Hexenstahl - I was aware that agencies of law and order do just that. They aren't above using zersetzung if it's simply too difficult to frame a legal charge.

 

[AddictivePersonality]

Hi, sorry I was going to create a whole new post but figured it’d be more convenient to just comment here… so I just started experimenting with ultra low dose naltrexone by mixing 1.5mg into 150ml of water approximately 2 days ago Monday and I Started at 2ml what I’m sure was .002mcg on top of my Methadone dose didn’t really notice anything so on my next dose 10hr later I went up to about .008mcg +MTD still nothing, so I went up to .015mcg +MTD in 10hr on the next dose still no difference, so finally I went up to .030mcg +MTD & not even a tickle of a difference… a little bit disappointed as I had high hopes thinking I’d at least feel something by now.. though I know I have an insane tolerance to opiates I don’t feel anything from them anymore and haven’t for years even after abstinence and even if I get clean for long periods I never feel better I’m pretty much permanently ruined. I will still try to titrate up fingers crossed I really could use some type of relief. Any pointers or suggestions are greatly appreciated thank you
~OneLove

 

[AddictivePersonality]

Hi, sorry I was going to create a whole new post but figured it’d be more convenient to just comment here… so I just started experimenting with ultra low dose naltrexone by mixing 1.5mg into 150ml of water approximately 2 days ago Monday and I Started at 2ml what I’m sure was .002mcg on top of my Methadone dose didn’t really notice anything so on my next dose 10hr later I went up to about .008mcg still nothing got so I went up to .015mcg 10hr next dose still nothing and finally .030mcg yet not even a tickle of a difference… a little bit disappointed as I had high hopes thinking I’d at least feel something by now.. though I know I have an insane tolerance to opiates I don’t feel anything from them anymore and haven’t for years even after abstinence and even if I get clean for long periods I never feel better I’m pretty much permanently ruined. I will still try to titrate up fingers crossed I really could use some type of relief. Any pointers or suggestions are greatly appreciated thank you
~OneLove

Sorry again y’all apparently I spoke too soon cause right after posting my reply I dosed approximately .060mcg then 100mg Methadone and a couple hours later I actually felt it working

 

[AddictivePersonality]

Weirdly enough, sense that last dose I reported I haven't been able to replicate it using the same amounts or more🫩 what an effing tease! One thing I noticed about 45mins after taking the uldn dose that worked, I started to feel like I was going into slight precipitated withdrawal symptoms and didn’t dose methadone until I felt I needed to stop myself from getting actually sick, so I’m thinking maybe that’s the indication to look for to tell me if it’s working or not.. I feel like it’s inconsistent therapeutically tbh, still experimenting though and will keep posting my results.

 

[Allylbenzene]

So, I took my first naltrexone dose last night ... I took one drop last night, which apparently was too much.

I think the person who encouraged you to try naltrexone overlooked important factors. They're well-intentioned but didn't consider your unique scenario, particularly body chemistry. If a doctor had done the same it would be deemed medical negligence (but doctors just follow guidelines which they can use as an 'excuse').

In your case, your body chemistry (ie general condition) seems to be in a fairly vulnerable state. You described methadone and amphetamine physiological dependency:

FYI, I take [160mg] methadone daily...since February, so I'm now totally physiologically dependent.
...
I had prescribed amphetamine on board (taken daily... used to be dex for years but had to switch to adderall)

Both buprenorphine and methadone have problematic effects (besides the opioidergic) which undermine proper body functioning. All conventional opioids have a disruptive influence on endocrine (hormonal) function which is worth taking seriously as this in-turn impacts metabolic function (ie disruption of the metabolic system).

Your chronic use of amphetamine meds will have incurred significant issues also. Amphetamine reliably disrupts hormonal regulation (outlined here) and the metabolic system (particularly the HPA axis). It helps "treat" ADHD via dopamine, noradrenaline, and activating "fight-or-flight" mode (aka stress response via HPA activation) which works via adrenaline. This helps produce hyperfocus & hypervigilence which "treats" ADHD but it has a broadly disruptive influence in the long-term.

Amphetamine also influences histamine (big link between opioids & histamine) and may have indirect opioidergic effects. This seems relevant to your experience with naltrexone.

So what I'm getting at is that these are fairly important factors which should inform your chosen strategy (whatever that may be).

5. There's another really weird data point. The day following the experience I described before, I tried 1/3 the dose (approx 1 mcg) of naltrex and was okay. Then, two nights following that, I experienced something similar but even more intense---without dosing the naltrexone again ... I have no idea what happened

Did you ever consider if naltrexone isn't appropriate for your current condition? It may be appropriate at a later date.
Putting aside methadone, I'd consider chronic use of amphetamine a key causative factor in your 'unexpected' reaction from naltrexone. Tbh I could see why it might be inexplicable & confusing if someone wasn't considering the bigger picture.

sounds to me like, if i want to approach tolerance reduction----naltrexone is preferable

Besides its opioid properties, naltrexone is particularly helpful thanks to it's property of TLR4 antagonism. Many things have this TLR4 blocking property, including dozens of otc items. There's other ways to reduce tolerances besides via TLR4. As an aside, it's worth considering that you'd be addressing the tolerance from 2 different drugs, amphetamine and methadone.

 

[4DQSAR]

Sorry again y’all apparently I spoke too soon cause right after posting my reply I dosed approximately .060mcg then 100mg Methadone and a couple hours later I actually felt it working

As I mentioned and provided evidence of, there is several orders of magnitude between LDN and ULDN and what EVERY study suggested was that the optimum dose between different patient could itself span at least two orders of magnitude.

All of the academic papers demonstrated that it apparently worked (although to be clear - it was the analgesic activity that was measured) but I suggest that is the reason why ULDN isn't simply the standard way opioids are prescribed. It's just too much work for a clinician to titrate every patient to their appropriate dose regime.

It was tried.

Oxytrex™ was a compound analgesic containing oxycodone and naltrexone, specifically 1ug of naltrexone per 1mg of oxycodone. But the ratio of the two medicines was fixed.

I don't THINK it's possible to patent the discovery, only to patent a new compound analgesic.

Don't forget, in virtually all cases, the euphoria and sedation produced by opioids are seen as SIDE EFFECTS. Ideally an analgesic should just control pain and produce no psychological alterations.

I say 'virtually all' because many nations seem to reserve at least one strong opioid whose use is limited to people in palliative care where the 'anxiolytic and sense of mental detatchment' activites ARE sought. After all, if someone has less than 6 months to live, developing physical dependence to a class of medication is a non-issue.

 

[AddictivePersonality]

As I mentioned and provided evidence of, there is several orders of magnitude between LDN and ULDN and what EVERY study suggested was that the optimum dose between different patient could itself span at least two orders of magnitude.

All of the academic papers demonstrated that it apparently worked (although to be clear - it was the analgesic activity that was measured) but I suggest that is the reason why ULDN isn't simply the standard way opioids are prescribed. It's just too much work for a clinician to titrate every patient to their appropriate dose regime.

It was tried.

Oxytrex™ was a compound analgesic containing oxycodone and naltrexone, specifically 1ug of naltrexone per 1mg of oxycodone. But the ratio of the two medicines was fixed.

I don't THINK it's possible to patent the discovery, only to patent a new compound analgesic.

Don't forget, in virtually all cases, the euphoria and sedation produced by opioids are seen as SIDE EFFECTS. Ideally an analgesic should just control pain and produce no psychological alterations.

I say 'virtually all' because many nations seem to reserve at least one strong opioid whose use is limited to people in palliative care where the 'anxiolytic and sense of mental detatchment' activites ARE sought. After all, if someone has less than 6 months to live, developing physical dependence to a class of medication is a non-issue.

Thank you for your reply!

I totally agree, seems like there is just way too many variations involved in using ULDN therapeutically with Opiates. Though I wonder if it’s just people who have less of a tolerance or opiate naive who benefit more from the combination.

I think hearing things like ULDN taking people back to Honeymoon phases and the almost night and day difference is what I’ve been trying to achieve. But honestly I would settle for any kind of relief from the pain of everyday. My last dose was about ULDN 125mcg + 60mg MTD approximately 2-3 hours ago with little to no affect. I’m a little confused because that one day of success when dosing ULDN 60mcg + 100mg MTD. Then tried to replicate it again with little to no effect so I figured to keep titrating up and havent been successful again since. One thing I am doing differently was when I was dosing lower ULDN I was dosing only 20mg at a time because of all the warnings of possible “newbie tolerance returning” until I dosed the 60mcg + 100mg because of feeling slightly icky. My regular dose atm is 60 mg twice daily which is a meh dose for me anyway, but anything more than 120mg a day and I can’t poop for Shit! “pun intended” lol and even then I have to get creative.. I get the 40mg White Methadose Wafers and have a pretty big stock pile.. so I’m not afraid of titrating up as far as needed in case I were to accidentally send myself into withdrawal, I definitely have enough MTD to keep myself well.

Anywho I will keep experimenting and report back. I think I might drop both doses down and see if I can replicate what I did before, a couple days of lower dose MTD then jump up one day after some discomfort sets in.. maybe that’s the only way it works for me idk or maybe I still need to titrate up the ULDN, how high do you think I could go until it’s probably not north it anymore? Im thinking maybe 200-250mcg…

 

[Allylbenzene]

I think hearing things like ULDN taking people back to Honeymoon phases and the almost night and day difference is what I’ve been trying to achieve.

From my perspective there are dozens of options for resetting tolerances besides naltrexone.
Naltrexone is just the most well-known and publicised option with the most studies which lends credibility for the public POV.

One of the key properties that makes naltrexone so helpful for opioid use is it's ability to block TLR4. Dozens of things share that same property, and many have other properties which also reduce tolerances. This has been discussed in other threads.

All classic opioids activate TLR4 which has undesirable effects, including increased pain sensitivity (hyperalgesia).

 

[AddictivePersonality]

From my perspective there are dozens of options for resetting tolerances besides naltrexone.
Naltrexone is just the most well-known and publicised option with the most studies which lends credibility for the public POV.

One of the key properties that makes naltrexone so helpful for opioid use is it's ability to block TLR4. Dozens of things share that same property, and many have other properties which also reduce tolerances. This has been discussed in other threads.

All classic opioids activate TLR4 which increases pain sensitivity, called hyperalgesia.

Do you happen to have any links or suggestions to said options?
I’ve tried sublingual Ketamine therapy before with little success. Though I do believe Ketamine does have some benefits itself.. I’ve also used DXM, Tagamet, antihistamines, Benzos, Grapefruit juice, Quinine, Muscle relaxers etc. religiously and they all use to work for potentiation purposes. Unfortunately not too much anymore.

I agree seems like ULDN has been a little more hyped up than anything else which is why I had such high hopes for it. What all have you heard of that could be more successful?
I’m willing to try anything at this points it’s been years since I’ve gotten any adequate pain relief from my medication. I’m going to get some Black Seed Oil as well on the 2nd to use sublingually.

 

[Allylbenzene]

I’ve tried sublingual Ketamine therapy before with little success. Though I do believe Ketamine does have some benefits itself.

Ketamine definitely has beneficial qualities but a few drawbacks also. It appears to interact with the opioid system but they don't yet know how.

I agree seems like ULDN has been a little more hyped up than anything else which is why I had such high hopes for it.

It's definitely a useful and valuable option for various purposes but it's not appropriate for everyone (as reported by @vima). Its popularity & prominence seems to detract from the other options which have therapeutic relevance.

Do you happen to have any links or suggestions to said options?
...
What all have you heard of that could be more successful?

Search the forums for TLR4, that'll bring up the relevant posts.

I’m willing to try anything at this points it’s been years since I’ve gotten any adequate pain relief from my medication.

Part of the issue is that medication increases sensitivity to pain (hyperalgesia). There are many analgesic options which don't have that issue, some are opioidergic, adenosinergic, GABAergic etc. The opioid system is one of many ways to approach this. One strategy is to fully reset & restore tolerances which means that all natural analgesics (including opioid-based ones) will work very well, and with the benefit of no tolerance issues nor side-effects. At least, incomparable to conventional opioids like methadone & codeine.

I’m going to get some Black Seed Oil as well on the 2nd to use sublingually.

Thymoquinone from black seed (Nigela sativa) is a good option with opioidergic qualities. There are dozens more, but blocking TLR4 is just as important imo.

Here's a few relevant quotes from academic articles on TLR4 & opioids:

Spoiler: TLR4 opioid link

...increased evidence indicates that...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

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

Further, representative members of clinically relevant opioids such as morphine, oxycodone, buprenorphine, methadone, pethidine/meperidine, and fentanyl showed efficacy in driving TLR4 signalling in a TLR4 overexpressing cell line
— 10.1016/j.bbi.2022.02.001

While the role of the immune system, specifically, Toll-like receptor 4 (TLR4) in drug-induced reward is becoming increasingly appreciated...
— 10.1016/j.bbi.2017.08.021

One such side effect is opioid-induced hyperalgesia (OIH), which includes a transition from opioid-induced analgesia to pain enhancement. Evidence in rodents supports the suggestion that OIH may be produced by the action of opioids at TLR4
— 10.1177/17448069241227922

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

...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

 

[4DQSAR]

@Allylbenzene - Naltrexone is the antagonist that has been studied by DOZENS of research teams all over the world for over four DECADES for it's ability to reverse tolerance to opioid agonists. More specifically, HUMAN trials. LARGE human trials. Heck, even candidate medications so cohorts in the region of THOUSANDS.

So why on earth would someone choose to go down the path that is far less well understood? Being purely pragmatic, how easy are these novel TLR4 ligands to obtain? The ones that turned out not to work in man as they did in rodent models...

I note that researchers view TLR4 ligands as possible tools to reduce or eliminate the psychological addiction to opioids (and stimulants and nicotine), not to reverse the tolerace in people who need to take potent opioids to control severe chronic pain.

Note the title of the thread!

 

[Allylbenzene]

So why on earth would someone choose to go down the path that is far less well understood?

When naltrexone (1) isn't appropriate for their scenario/body condition (as vima reported) or (2) doesn't genuinely meet their requirements as alluded here:

...hearing things like ULDN taking people back to Honeymoon phases and the almost night and day difference is what I’ve been trying to achieve.

Certainly ULDN can produce this state as confirmed by myriad reports, but it's arguably fairly superficial compared to a genuine "full" reset. Such a reset would involve restoring the metabolic system, endocrine system, dopaminergic system to name but a few; the idea being to restore coherence and encourage built-in repair capabilities. This goes far beyond the opioidergic system.

For this persons scenario/condition, they require a genuine reset, in-which ULDN can probably play a part.

I have an insane tolerance to opiates I don’t feel anything from them anymore and haven’t for years even after abstinence and even if I get clean for long periods

So, a secondary response to your question:

So why on earth would someone choose to go down the path that is far less well understood?

Why would someone intentionally limit their chances of fully reversing their tolerances by only considering naltrexone?

Being purely pragmatic, how easy are these novel TLR4 ligands to obtain?

I wouldn't overcomplicate things, TLR4 blocking capability exists in fairly common items besides naltrexone. Items which can be purchased by anyone in the US/UK/EU without resorting to questionable "grey market" outlets.

I note that researchers view TLR4 ligands as possible tools to reduce or eliminate the psychological addiction to opioids...not to reverse the tolerace in people who need to take potent opioids to control severe chronic pain.

Researchers perceptual breadth isn't necessarily always appropriate for use as a guideline nor "benchmark". Their unacknowledged or unintentional dogma sometimes clouds their interpretation which can lead to incomplete assessments and oversights. Often they interpret ligands in a compartmentalised manner which hinders their ability to appreciate & understand the wider context. This sort of thing often leads to iatrogenic harm. I digress.

The majority of existing OTC TLR4 antagonists present other synergistic MOA conclusive to the goal of resetting tolerances. This implies dozens of OTC items are capable of achieving this, but none qualify for a patent thus the funding is never allocated and clinical trials never occur. In other words, from an evidence-based perspective these options don't exist.

The most popular and well-researched TLR4 antagonist is probably naltrexone. As for the others, there's a good assortment listed here.