LDN for reducing opioid tolerance

[copium7777]

I use opioids both for pain and recreationally/mood uplift. but unless you're doing h, theyre damn expensive. also, the development of tolerance to the analgesic and euphoric effects happens faster than the devleopment of tolerance to side effects such as respiratory depression and constipation.



I take oxy either one or two days a week and am trying to keep my dose steady. I had read a little on ultra low dose naltrexone and low dose naltrexone for attenuating opioid tolerance and side effects, and i was prescribed it for pain/inflammation anyway, so I have decided to try and use it to help keep my tolerance reasonable. It seems very promising but I don't have any idea if there's a bunch of solid evidence on the dose range or schedule needed to totally reset tolerance.


[This](https://www.ncbi.nlm.nih.gov/pubmed/20398374) study shows ultra low dose naltrexone attenuating morphine tolerance in rats. [This one] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5469510/ shows that adding uldn to oxycodone attenuates hyperalgesia that can occur in long term opioid use for chronic pain. There was a drug in development, oxytrex, that was a combination of oxy and ultra low dose naltrexone, to help attenuate side effects/tolerance to oxy, idk why it never came to market.

ULDN is a way lower dose range than LDN. It seems like LDN is not used in these studies bc it is more likely to either block some of the analgesia, or precipitate withdrawals, which could be nightmarish especially in chronic users. But since im not dependent on opioids, im more comfortable getting near that boundary, and it seems like the higher dose range of LDN might be more helpful in actually reversing tolerance, whereas uLDN only slightly attenuates it. I also read a now-deleted post from r/opiates in which someone said LDN, not uLDN, totally keeps them from gaining tolerance, but they had to start the LDN before the opioids and take it daily.

Also kratom users sometimes take stem and vein kratom, which has more of the opioid antagonists and less agonists, to reset their tolerance, and it seems to work well.

I had an experience with too high a dose of LDN (I believe it was 1.5 mg) taken too soon after my opioid dose, seemed to cause dysphoria and negative symptoms. But when taken after the opioid effects totally wear off, it has few side effects, so maybe I should be dosing higher? My dose is usually like .5 mg a day.

The theory is that it upregulates opioid receptor density in response to a partial blockade. this is part of my theory of why LDN works for some chronic pain patients, on its own, that it increases opioid recceptor density so ones sensitivity to ones own endorphins is way higher. From personal experience/anecdote in the past i felt like it took about five days of 1 to 1.5 mg doses of LDN before i was experiencing "getting extremely high off my own endorphins". I did experience some episodes of agitation, insomnia, and hypertension from the LDN, but I don't think thats normal, and the hypertension wasn't too bad.

​

So all in all, it seems like there are a few studies on uLDN for this purpose, promising but not a ton of evidence, a bunch of anecdotes, and very few studies on LDN for resetting tolerance (although there are studies on its use as an antiinflammatory and for chronic pain, like [this one] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3962576/ , from which we might infer it could help with tolerance?)

​

This was a little bit rambling but I guess I'd be interested in any form of evidence on this topic, anecdotal or published, since the existing evidence is so scant. Has anyone here had experience with uldn or LDN for tolerance? Has anyone found good posts on reddit or forums about it? or good studies?

​

despite chipping fairly judiciously I seem to have built up some level of tolerance, maybe bc w high doses you can have rapid tachyphylaxis without even taking it for very long. One other thing I was thinking of is using nmda antagonists as well, to help prevent too much tolerance buildup.

 

[copium7777]

Any thoughts ???

 

[copium7777]

Very low dose naltrexone addition in opioid detoxification: a randomized, controlled trial

Although current treatments for opioid detoxification are not always effective, medical detoxification remains a required step before long-term interventions. The use of opioid antagonist medications to improve detoxification has produced inconsistent ...

www.ncbi.nlm.nih.gov

Very low dose naltrexone addition in opioid detoxification: a randomized, controlled trial
Paolo Mannelli, Ashwin A. Patkar, [...], and Edward Gottheil

Additional article information

Abstract
Although current treatments for opioid detoxification are not always effective, medical detoxification remains a required step before long-term interventions. The use of opioid antagonist medications to improve detoxification has produced inconsistent results. Very low dose naltrexone (VLNTX) was recently found to reduce opioid tolerance and dependence in animal and clinical studies. We decided to evaluate safety and efficacy of VLNTX adjunct to methadone in reducing withdrawal during detoxification. In a multi-center, double-blind, randomized study at community treatment programs, where most detoxifications are performed, 174 opioid-dependent subjects received NTX 0.125 mg, 0.250 mg or placebo daily for 6 days, together with methadone in tapering doses. VLNTX-treated individuals reported attenuated withdrawal symptoms [F = 7.24 (2,170); P = 0.001] and reduced craving [F = 3.73 (2,107); P = 0.03]. Treatment effects were more pronounced at discharge and were not accompanied by a significantly higher retention rate. There were no group differences in use of adjuvant medications and no treatment-related adverse events. Further studies should explore the use of VLNTX, combined with full and partial opioid agonist medications, in detoxification and long-term treatment of opioid dependence.
Keywords: Community treatment programs, craving, opioid agonist/antagonist interaction, opioid antagonist, opioid dependence, opioid withdrawal

 

[polymath]

The theory is that it upregulates opioid receptor density in response to a partial blockade. this is part of my theory of why LDN works for some chronic pain patients, on its own, that it increases opioid recceptor density so ones sensitivity to ones own endorphins is way higher. From personal experience/anecdote in the past i felt like it took about five days of 1 to 1.5 mg doses of LDN before i was experiencing "getting extremely high off my own endorphins". I did experience some episodes of agitation, insomnia, and hypertension from the LDN, but I don't think thats normal, and the hypertension wasn't too bad.

The prevention of opioid tolerance by low dose naloxone or naltrexone is believed to be a result of filamin A binding.

High-Affinity Naloxone Binding to Filamin A Prevents Mu Opioid Receptor–Gs Coupling Underlying Opioid Tolerance and Dependence

Ultra-low-dose opioid antagonists enhance opioid analgesia and reduce analgesic tolerance and dependence by preventing a G protein coupling switch (Gi/o to Gs) by the mu opioid receptor (MOR), although the binding site of such ultra-low-dose opioid antagonists was previously unknown. Here we...

journals.plos.org

 

[MsDiz]

This is something I’ve been researching recently actually. Not for your specific reasons but that LDN has been used for people with pain successfully. As someone who is young and who will be on pain medication for life due to a degenerative condition I worry about the tolerance I am gaining to my current opioid. It’s only going to increase and I’ll be moved to stronger medications which I would like to delay for as long as possible. I actually do tolerance breaks on my own because the drs here are idiots but it’s helped me stay at a relatively low dose of opioids for the pain I experience. For example I regularly dislocate my hip and many other joints. People with my condition and my dislocations are generally on fent lollies at this stage so I’ve done well so far. I’ve also a pretty high pain threshold and I admittedly do accept a higher pain tolerance because I’d rather not medicate heavily.

I’m sorry I’ve no answers for you but it’s interesting reading for sure.

 

[copium7777]

Same, @PrincessDiz

I have chronic pain due to a connective tissue problem that I may need to have surgery for. I do like to take enough pain meds to get euphoria too but there's 100 percent a therapeutic aspect. And it seems like the main problem with opioid pain meds is gaining tolerance. ThTs why when studied they don't seem to work long term for chronic pain despite being first choice for acute pain.

Kratom is possibly an option but since I have POTS and autonomic issues even the red strains cause some heart racing and stuff. I used to love it.

Nsaids are.. not so good to take daily. Ketamine I'm prescribed and it's pretty decent but short lasting and I'm not prescribed a high enough doses to take away my pain a significant portion of the day

 

[MsDiz]

Same, @PrincessDiz

I have chronic pain due to a connective tissue problem that I may need to have surgery for. I do like to take enough pain meds to get euphoria too but there's 100 percent a therapeutic aspect. And it seems like the main problem with opioid pain meds is gaining tolerance. ThTs why when studied they don't seem to work long term for chronic pain despite being first choice for acute pain.

Kratom is possibly an option but since I have POTS and autonomic issues even the red strains cause some heart racing and stuff. I used to love it.

Nsaids are.. not so good to take daily. Ketamine I'm prescribed and it's pretty decent but short lasting and I'm not prescribed a high enough doses to take away my pain a significant portion of the day

I have a connective tissue disorder! Ehlers-danios syndrome hypermobility type. I don’t have POTS but I do have orthostatic hypotension. I have UC as well so I can’t take nsaids which sucks. Don’t think I’d manage well getting prescribed ketamine! It was too amazing to me in the past recreationally! Lol I don’t abuse my opioids at all thankfully.
But yea, this is an interesting topic you brought up.

 

[copium7777]

I have a connective tissue disorder! Ehlers-danios syndrome hypermobility type. I don’t have POTS but I do have orthostatic hypotension. I have UC as well so I can’t take nsaids which sucks. Don’t think I’d manage well getting prescribed ketamine! It was too amazing to me in the past recreationally! Lol I don’t abuse my opioids at all thankfully.
But yea, this is an interesting topic you brought up.

Word. I haven't been formally diagnosed with EDS or marfans but I have craniocervical instability without having had head trauma so it's suspected that I have a connective tissue disorder

Although I also got the connective tissue problems after infection and mold exposure so they could have an environmental origin rather than genetic , it could be both, bc most people don't just have their ligaments melt from one Lyme infection and mold exposure lol

In the past I was prescribed IV saline for my low blood volume, pots and orthostatic issues. It really helped.

 

[MsDiz]

Word. I haven't been formally diagnosed with EDS or marfans but I have craniocervical instability without having had head trauma so it's suspected that I have a connective tissue disorder

Although I also got the connective tissue problems after infection and mold exposure so they could have an environmental origin rather than genetic , it could be both, bc most people don't just have their ligaments melt from one Lyme infection and mold exposure lol

In the past I was prescribed IV saline for my low blood volume, pots and orthostatic issues. It really helped.

It took me 27 years to get my EDS diagnosis and that was because I paid to go see a specialist. Drs in Ireland/UK don’t know shit about it. I hope you find one who does wherever you live! Get the diagnosis and get the treatment plans in place. It makes so much difference. My physical therapy changed my life.

 

[G_Chem]

The prevention of opioid tolerance by low dose naloxone or naltrexone is believed to be a result of filamin A binding.

High-Affinity Naloxone Binding to Filamin A Prevents Mu Opioid Receptor–Gs Coupling Underlying Opioid Tolerance and Dependence

Ultra-low-dose opioid antagonists enhance opioid analgesia and reduce analgesic tolerance and dependence by preventing a G protein coupling switch (Gi/o to Gs) by the mu opioid receptor (MOR), although the binding site of such ultra-low-dose opioid antagonists was previously unknown. Here we...

journals.plos.org

This may explain why Suboxone is the only opiate I can taper and/or maintain at a certain dosage, without rising tolerance.

In regards to OP, I plan on trying this soon with LDN. I’m going to get prescribed for cancer as I hear it can reduce/eliminate tumors, but this would be an extra benefit.

-GC

 

[polymath]

This may explain why Suboxone is the only opiate I can taper and/or maintain at a certain dosage, without rising tolerance.

That's also what I thought, the naloxone probably has enough bioavailavility for this effect even when dosed sublingually.

 

[dopamimetic]

I would go for ULN and if possible, do a test with naloxone before ... naltrexone has a bloody long half life and if you get anything remote like I got from accidental expose to naloxone when I was opioid-naive, you want to stay the hell away of high doses of these chemicals. They aren't plain antagonists but inverse agonists, strangely some people can take like 50mg naltrexone without any acute effects but when I in endless wisdom of youth snorted part of a tilidine-naloxone pill it gave me a hour of dysphoric hell. A river of tears, I felt like the single most lonely person in the world, without any real reason... (probably I have some sort of ASD which is associated with excess of endogenous opioids, and I was on memantine to that time, still I never found any report that would confirm/explain my experience)

Yeah, been curious about ULN/LDN for quite long time but never found the will to touch this stuff again.

 

[copium7777]

for what its worth i've also taken plenty of LDN , not just ULDN, sometimes while taking opioids, without anything close to going through hell although its had short lasting adverse effects.

 

[CfZrx]

Any thoughts ???

Yes, one thing I've observed is that rumors on Bluelight are not always correct, and that means we really have to experiment ourselves. Good luck, I can't offer any tips on this one

 

[copium7777]

Yes, one thing I've observed is that rumors on Bluelight are not always correct, and that means we really have to experiment ourselves. Good luck, I can't offer any tips on this one

i posted evidence for its use, not just rumors.

 

[copium7777]

It took me 27 years to get my EDS diagnosis and that was because I paid to go see a specialist. Drs in Ireland/UK don’t know shit about it. I hope you find one who does wherever you live! Get the diagnosis and get the treatment plans in place. It makes so much difference. My physical therapy changed my life.

The Mechanical Basis of ME/CFS Craniocervical Instability, CCI, Tethered Cord

ME, POTS, and now an extremely erratic heart rate? It was due to the CCI compressing my brainstem!

www.mechanicalbasis.org

 

[CfZrx]

i posted evidence for its use, not just rumors.

But even the "evidence" these days is wack. Like take suboxone, where the evidence is that it is all these things that it is not or vice versa. I still have learned I must undertake my own experiments and take what i lear on here w/ a grain of salt.

 

[dopamimetic]

Does this only work while on opioids, when tolerance is low to prevent it from rising or actually counters tolerance?
I am struggling to fight withdrawal of 200+mg morphine with memantine (yesterday 80mg which finally took most but still some physical distress, lethargy coupled with insomnia, headache, heavy yawning, runny nose, nausea). As where I live atm most medicine is without Rx, guess I could get a box of naltrexone tomorrow and create solution again. If ULN would be of help even in withdrawal, which I question somewhat?

(I want to take this chance to quit opioids, so e.g. tramadol isnt an Option. They have messed me up for too long now, were an absolutely shitty propose by Zürich addiction center for getting off dissociatives. Never worked and became my first true addiction.)

 

[copium7777]

Im really curious about the memantine. I wonder if adamantane would work as well since i have some of that (made another thread on this)

Ldn seems to be working pretty well at keeping tolerance minimal but not absolutely nil. I could probably take higher doses tho, i normally only take btwn .5 mg and 1 mg. Usually just .5 mg. im just running out, thats the thing. But 1.5 mg or 2 mg every day or more could probably knock out tolerance totally in two or three days, reset it to opioid naive levels!

 

[dopamimetic]

I can't really answer this but I guess adamantane has poor ability to penetrate the brain; all of the medicinal derivates have that nitrogen rest on it like amantadine, memantine, etc.. and when comparing amantadine and memantine, the former is a much weaker NMDA antagonist that will have more side effects and less specific activity. I remember one trip report of an "overdose" of amantadine around 2g I believe, that consisted of weird visuals and sounded more anticholinergic than anything else so I wouldn't spend much hope there ...

... but, as there appears to be next to no data about in-vivo use of adamantane, and maybe there's a reason for it to be sold, I am still interested in it. Wouldn't guinea pig it myself though unless more info.

Memantine is a weird one. Yeah, it takes almost every symptom of opioid withdrawal, you don't feel like shit, no depression, no loneliness, no anxiety, no sweats, no puking, but you're still withdrawing - for me, I feel how much energy my body needs to do all these changes, today I slept most of the day and felt heavy tiredness.. but compared to cold w/d it's really a walk in the park. Guess together with low-dose amphetamine and/or some lope it would catch all.
Also the potentiation is real shit. 10mg of morphine felt yesterday almost like 200mg before, not exactly, in that it's more clear but the strength is there...

Papers tell 10mg memantine is enough to do a some 5x potentiation of opioids or more but that is in opioid naive rats. Start slow, as said the potentiation is real and heavy - you won't die of it though, I guess it doesn't affect the respiratory depression as I did other, more potent dissociatives before while continuing on the same dose of morphine without physically ill effects. For w/d be prepared to require way more than 20mg. Even with 80mg I don't feel the slightest hint of dissociation now.