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Author Topic: (Reddit: drugnerds) taking ultra low dose naloxone for anhedonia.  (Read 5452 times)

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Source: https://www.google.com/amp/s/amp.reddit.com/r/DrugNerds/comments/9hsitr/widthdrawl_from_naloxone/

redddit/DrugNerds

u/EnduringInsanity
Sep 21, 2018, 6:04 PM

Widthdrawl from naloxone

This might be a really stupid questions but I cant stop thinking about it. Lets say a opiate naive individual kept taking naloxone for a long period, enough to get "addicted" to it. Would stopping it cause a widthdrawl that would feel like a opiate high? My theory is that prolonged exposure to naloxone would cause upregulation of opioid receptors causing them to be super sensitive to endogenous endorphins thus resulting in a high when sober

41 Comments
22
Valo-FfM • Sep 21, 2018, 6:54 PM
If one takes Naloxon long enough to cause upregulation of the opioid-receptors or increased sensitivity to endogen endorphins to reach homeostasis again than it is possible that there would be an opioid-like effect by the end of the intake of Naloxon and as long as it takes the body to downregulate sensitivity this effect could last.

It could go the other way around as well though and by increased opioid-receptor density but equal distribution of endorphins there could be long-lasting lack of endorphin activity in the brain until the brain downregulates opioid-receptor density.

And it is also possible that the brain does not recognize a lack of activity, because the opioid-receptors are seemingly occupied even though they are effected in an adverse way compared to normal receptor-activity.

18
rekaikutan • Sep 21, 2018, 7:38 PM
I remember reading about people taking kappa opioid (dysphoric) agonists to downregulate them which causes increased hedonic activity.

Also, I talked with someone in drugnerds taking ultra low dose naloxone for anhedonia. He said it worked really well, it was prescribed by his MD as well.

11
jskafsjlflvdodmfe • Sep 21, 2018, 8:11 PM
I was on Suboxone for about 3 years, starting with a 8mg daily dose. After 6 months I had tapered down to a quarter tablet, ~2mg. Around this time the sublingual film strips came out, and I was given a bunch of coupons to get them for free or like 5 dollars. Because of the lack of cost I figured I would stay on them longer and continue my slow taper. By the end of year 2 I was cutting the strips in 20 pieces, and the 1/20th piece still provided the same effect as the whole 8mg tablets I had in the beginning. When I lowered the dose each time, once any initial discomfort was over and I was 'normalized', the effects always felt the same and consistent, no matter the dose. Over the third year I had tapered down to a tiny 1/100th of a strip. Due to the difficulty in cutting the pieces so small (should have used volumetric dosing in retrospect) the size of the pieces would of course be slightly inconsistent, but I took extreme care cutting them so I would think the variation couldn't have been more than +/- 10%. During this time if I had accidentally taken one of the very slightly larger pieces the effect would be dramatic, to the point where I would be nodding, nauseated, and as high as ever before (with only maybe ~0.09mg max!!). I knew practically nothing about chemistry and pharmacology then so I never understood what was happening.

Now it seems that this increased sensitivity was caused by the ultra low dose use, but to the extent of whether it was the buprenorphine, the naloxone, or the combination is uncertain. I believe much research into this area is needed, but there is certainly something interesting going on.

EDIT: Seems everything could be explained from this paper.

https://www.ncbi.nlm.nih.gov/pubmed/18253501

9
[deleted] • Sep 22, 2018, 1:19 AM
[deleted]

1
jskafsjlflvdodmfe • Sep 22, 2018, 4:06 AM
Well I don't think I can say that, I didn't know what I was doing at the time, total accident. It was effective for me, completely eliminating my tolerance, and made getting off it a breeze. I can't say I recommend doing so as it can be difficult not to abuse it with such a low tolerance and I wouldn't recommend suboxone in general.

1
[deleted] • Sep 22, 2018, 5:31 AM
[deleted]

1
jskafsjlflvdodmfe • Sep 22, 2018, 6:29 AM
What does of d-amp were you using, and how long did it take for you to notice recovery/reduced tolerance?

1
darsinagol • Sep 22, 2018, 3:21 AM
Naloxone doesnt have much bioavailability when taken orally. The suboxone strips are for the buprenorphine. The naloxone is added so that if one tries to dissolve and shoot it up (or some other ROA) the naloxone will. eat the opiate to the receptor and kill the buprenorphine high before it starts.

1
jskafsjlflvdodmfe • Sep 22, 2018, 3:57 AM
The sublingual bioavailability is similar for both, which is how it was consumed, and at such low doses that is almost irrelevant. But I just found this paper which pretty much explains everything I experienced.

"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 show that with approximately 200-fold higher affinity than for the mu opioid receptor, naloxone binds a pentapeptide segment of the scaffolding protein filamin A, known to interact with the mu opioid receptor, to disrupt its chronic opioid-induced Gs coupling. Naloxone binding to filamin A is demonstrated by the absence of [(3)H]-and FITC-naloxone binding in the melanoma M2 cell line that does not contain filamin or MOR, contrasting with strong [(3)H]naloxone binding to its filamin A-transfected subclone A7 or to immunopurified filamin A. Naloxone binding to A7 cells was displaced by naltrexone but not by morphine, indicating a target distinct from opioid receptors and perhaps unique to naloxone and its analogs. The intracellular location of this binding site was confirmed by FITC-NLX binding in intact A7 cells. Overlapping peptide fragments from c-terminal filamin A revealed filamin A(2561-2565) as the binding site, and an alanine scan of this pentapeptide revealed an essential mid-point lysine. Finally, in organotypic striatal slice cultures, peptide fragments containing filamin A(2561-2565) abolished the prevention by 10 pM naloxone of both the chronic morphine-induced mu opioid receptor-Gs coupling and the downstream cAMP excitatory signal. These results establish filamin A as the target for ultra-low-dose opioid antagonists previously shown to enhance opioid analgesia and to prevent opioid tolerance and dependence."

https://www.ncbi.nlm.nih.gov/pubmed/18253501

1
iammyowndoctor • Sep 27, 2018, 9:39 AM
What you just read is correct, man. With suboxone for example, you can get high on it indefinitely without needing to increase the dose or losing strength of effect. All that increases is the speed at which it's metabolized.

I know this because I doing myself, and have been for the last 8 months or so.

1
Some90sScreenName • Nov 28, 2018, 8:00 PM
I have heard of this from a guy I know, and he said that the tolerance does not increase by much at all. It is quite scary to think about. He said he only upped his dose after about 3 months. The only problem is the fact that the withdrawal can last months after stopping it from withdrawals.

1
•iammyowndoctor • Nov 28, 2018, 8:48 PM
The only problem is the fact that the withdrawal can last months after stopping it from withdrawals.

I'm not sure this is really true. It's certainly never happened to me anyway. I mean you will get some symptoms that last a while, like diarrhea for one will continue for months typically, but besides that you certainly do not feel like shit for more than a week or so, IME.

Actually, went I detoxed from high dose benzos and opioids (and meth) last year, as soon as the bulk of the withdrawal was over, I started to feel really great, extremely optimistic, even though I was still technically feeling the withdrawal, my mood just improved so much that it didn't get me down.

So yeah, please don't buy into the idea that that will happen, it can really get you down, and sometimes depression can make withdrawal seem longer than it really is. I mean if you've really fucked up your life on dope, you probably will feel depressed after detoxed, I guess I did good that I didn't quite mess up my whole life, because this didn't happen to me. In fact, the dependency itself was really getting me down, I thought it would take years to taper down off of everything, so when I finally got thru with the bulk of the withdrawal, I felt like a million bucks not to have that weight on my shoulders anymore.

1
• •Some90sScreenName • Nov 29, 2018, 3:30 AM
I am not sure what your doses were, but withdrawal is not in any way as easy as you are making it sound. It is known that suboxone and methadone withdrawal are some of the longest withdrawals out there. Maybe you were in a clearer head space, but may addicts are not. I agree that the weight is gone, but that is only one problem. I am glad you are no longer dependent, but the way you make light of addiction is a bit concerning.

1
• • •iammyowndoctor • Nov 29, 2018, 12:31 PM
Haha. Lol, nah I'm dependent again. The difference is this time I don't feel bad about it though, but tolerance goes up at a snail's pace despite getting high pretty much everyday.

1
iammyowndoctor • Sep 27, 2018, 9:36 AM
During this time if I had accidentally taken one of the very slightly larger pieces the effect would be dramatic, to the point where I would be nodding, nauseated, and as high as ever before (with only maybe ~0.09mg max!!). I knew practically nothing about chemistry and pharmacology then so I never understood what was happening.

Are you saying this happened to you? Or it's what you expected would happen? I confused on whether you actually did get this effect from so small a dose. Very interesting indeed if so.

1
tristeza_xylella • Sep 21, 2018, 7:45 PM
LDN is a popular "experimental" treatment for MS. I havent seen any fellow MS-ers have side effects other than they wont be taking any opiate pain killers for dental work....

4
jskafsjlflvdodmfe • Sep 21, 2018, 8:27 PM
I believe you are referring to Naltrexone, not Naloxone.

9
tristeza_xylella • Sep 21, 2018, 8:37 PM
Yes. I'm sorry. This is the 2nd drug/healthcare mistake I've made on reddit in 12 hours time. Hanging head in shame:( tis hard to accept I am more patient (MS) than professional (RN) and drug nerd Guinea pig.

3
jskafsjlflvdodmfe • Sep 21, 2018, 8:54 PM
Oh its cool, I still mix the two up in casual conversation. I was mainly replying because I was curious if you were indeed talking about LDN using naloxone in place of naltrexone. I'm sure it could be used similarly, but I haven't seen any clinical usage. Though naloxone has a much faster onset, faster elimination, and different metabolites, maybe it wouldn't be as effective. Also, one of the two, I forgot which, has an active agonist metabolite, which could also play a role in therapeutic effects.

2
tristeza_xylella • Sep 23, 2018, 1:48 AM
Easier to call it "Narcan" and "LDN." But then we wouldn't be proper nerds.

1
recoverycat • Sep 22, 2018, 2:12 AM
Don't worry about it, I work in pharmacy and I have to think for a minute before remembering which is which.

2
dynamitemcnamara • Sep 21, 2018, 8:45 PM
Yeah it's naltrexone.

I'm interested to see if more studies will show that it really is efficacious in treating autoimmune diseases, the evidence so far seems promising.

2
AlkaliActivated • Sep 21, 2018, 8:44 PM
I believe they are functionally the same, and can work interchangeably in that protocol.

1
darsinagol • Sep 22, 2018, 3:19 AM
From my understanding the naloxone is a competitive antagonist to the opioid receptor. Which means they bind but don't activate. Would this still cause up regulation?

1
LacklusterIsomer • Sep 21, 2018, 8:43 PM
This is a really cool thought. Im just typing my minds thoughts so take that for what it is.

We know opiod addicts cant get through their withdrawal faster by taking naloxone. Yes it throwa you into withdrawal instantly but there is a specific term for it, its not actually upregulating or speeding up the process.

With that said, do we know what effect naloxone has when administered to someone who is not dependent on opiods or overdosing?

The body and mind always try to regulate, aka homeostasis, so any sustained change will result in some sort of effect I believe. We should consider how long Naloxone is active after administered while taking into account the change it makes on the sober brain.

If it is a dysphoric state that is prolonged indefinitely through continual persistant (or peak/slope) administration, I'd theorise even on a basic level, much like if you were tortured for some time, its action ceasing alone would feel 'better".

I think it would be a stretch to compare that to a high though. More a relief than anything.

I could be way off, just speaking my mind

4
freakorgeek • Sep 21, 2018, 9:17 PM
there is a specific term for it

Precipitated withdrawal.

5
LacklusterIsomer • Sep 21, 2018, 10:31 PM
Thanks man, yeah i was drawing a blank there.

1
iammyowndoctor • Sep 27, 2018, 9:42 AM
We know opiod addicts cant get through their withdrawal faster by taking naloxone. Yes it throwa you into withdrawal instantly but there is a specific term for it, its not actually upregulating or speeding up the process.

I believe it does actually. At least in instance of flumazenil with benzos anyway, look that med up on wikipedia it should be there. If it works there, I'd bet it would with opioids too.

Opioid antagonists have very little effect on someone not dependent on opioids. I've seen it myself in rehab. Two buddies of mine took the vivotrol shot, next day they're just eating lunch calmly as ever, as if nothing happened. I ask them, they say they feel the same.

1
Bluhah78 • Sep 30, 2018, 6:42 PM
It is clear you do not know how a receptor blockade of mu opioid works, your example is meaningless.

1
iammyowndoctor • Oct 1, 2018, 4:51 AM
I do man. Did you think "receptor blockade" meant "all receptors are totally off limits from any other kind of agonist/antagonist? That is not what it means dude. It only means that enough of them are blocked (at any one time) to prevent weaker binding drugs from having an overall effect on the body.

1
lulumeme • Jan 20, 2019, 10:58 AM
It's not comparable to a high, sure, but most people participating in low dose naltrexone, are typically recovering addicts, who are clean and use it for depression or pain, because it works better than standard antidepressants like SSRI's. The mild moodlift is more apparent and useful than the emotion numbing ssri effect

1
jskafsjlflvdodmfe • Sep 21, 2018, 8:44 PM
This is more or less how low dose naltrexone therapy works for PAWS, recovering opioid addicts, and probably other treatments as well. The nightly LDN dose causes a rebound effect the next day, with the effects of endogenous endorphins being much more pronounced through out the day, providing a modest relief. Over the long term, I assume that this can achieve significant up-regulation to the same level's as before opioid use and down-regulation occurred. I don't believe the up-regulation would be beyond 'normal' levels, to achieve a significant high when sober. Most likely, what you describe would lead to a day or two of a modest runners high type feeling, then homeostasis would normalize the person very quickly.

5
babunal • Sep 21, 2018, 8:21 PM
LDN has also been successfully used to treat ulcerative colitis.

4
whersmaihart • Sep 21, 2018, 8:37 PM
LDN is naltrexone, not naloxone

5
Some90sScreenName • Nov 28, 2018, 8:05 PM
The two are similar because it bonds to the mu opioid receptors. That can have an impact on digestion and how the intestines work.

1
Dctr_K • Sep 21, 2018, 6:25 PM
Interesting theory, not sure if thats the case tho. Maybe some one will chime in with some info

3
EnduringInsanity • Sep 22, 2018, 2:11 AM
So naloxone does have some effects when administered to a non tolerant individual not euphoric nor dysphoric but mostly just a sedative with some other effects. https://psychonautwiki.org/wiki/Naloxone Because of the emotion suppression it makes me believe it could lead to anxiety during widthdrawl and maybe some benzo like widthdrawl effects?

1
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1
Giboras • Sep 26, 2018, 3:51 PM
Naloxone doesnt just antagonize the mu-opioid receptor, but the kappa as well (not as strong, but still).
Kappa-Opioid receptor activaton is associated with dysphoria and anxiety.
Antagonizing them with Naloxone will most likely cause them to upregulate.
When discontinuing the Naloxone, more Kappa Receptors could be presnt and could lead to dysphoria. (until homeostasis).
The possible heightened mu-opioid receptor count cound cancel that out.

1
rogueMD39 • Sep 26, 2018, 11:38 PM
This is a common phenomenon in patients that take specifically low doses of naltrexone or naloxone. It doesn't seem to happen often in patients at the normal dose range. I'm not quite sure why

1
iammyowndoctor • Sep 27, 2018, 9:44 AM
IME, opioid antagonists have basically no effect on people not dependent on agonists. I saw two buddies in rehab get on vivotrol, they literally did not change one bit afterwards, and said they felt the same as well.

I'm not sure why this is but I want to get to the bottom of it too. Great question btw, thought of it many times myself as you can see.

1
kratonian • Oct 17, 2018, 7:16 AM
i have been dependant on opiates on and off for years, after trying all kinds of meds from a-z from my TRD / MDD



Opiates, particularly full agonists like heroin, were the only drugs that relieved all my symptoms of depression and anxiety. Anyways, after mutliple failed detox attempts, many different opiates/opioids, I relapsed on heroin and cocaine and was speeballing daily for a few months and went through large amounts, felt great though. Finally after years of contemplating, I just got on sub (zubsolv). They started me on 5.7mg 3x a day, which seems like a lot, but im on day 2 and feel like absolute crap.



I just want the antidepressant effect I got from full agonists, and I just want to be functional again, I know this will take some time, esp. because of the cocaine abuse. But what can I change/add to this regimen to make it more effective at combating my depression/upregulating opiate receptors?



I have access to LDN/ULDN but I doubt thats of any use here

1
rekaikutan • Sep 21, 2018, 7:28 PM
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Post Merged: May 04, 2019, 04:56:38 PM
Source: https://www.google.com/amp/s/amp.reddit.com/r/DrugNerds/comments/9hsitr/widthdrawl_from_naloxone/

redddit/DrugNerds

u/EnduringInsanity
Sep 21, 2018, 6:04 PM

Widthdrawl from naloxone

This might be a really stupid questions but I cant stop thinking about it. Lets say a opiate naive individual kept taking naloxone for a long period, enough to get "addicted" to it. Would stopping it cause a widthdrawl that would feel like a opiate high? My theory is that prolonged exposure to naloxone would cause upregulation of opioid receptors causing them to be super sensitive to endogenous endorphins thus resulting in a high when sober

41 Comments
22
Valo-FfM • Sep 21, 2018, 6:54 PM
If one takes Naloxon long enough to cause upregulation of the opioid-receptors or increased sensitivity to endogen endorphins to reach homeostasis again than it is possible that there would be an opioid-like effect by the end of the intake of Naloxon and as long as it takes the body to downregulate sensitivity this effect could last.

It could go the other way around as well though and by increased opioid-receptor density but equal distribution of endorphins there could be long-lasting lack of endorphin activity in the brain until the brain downregulates opioid-receptor density.

And it is also possible that the brain does not recognize a lack of activity, because the opioid-receptors are seemingly occupied even though they are effected in an adverse way compared to normal receptor-activity.

18
rekaikutan • Sep 21, 2018, 7:38 PM
I remember reading about people taking kappa opioid (dysphoric) agonists to downregulate them which causes increased hedonic activity.

Also, I talked with someone in drugnerds taking ultra low dose naloxone for anhedonia. He said it worked really well, it was prescribed by his MD as well.

11
jskafsjlflvdodmfe • Sep 21, 2018, 8:11 PM
I was on Suboxone for about 3 years, starting with a 8mg daily dose. After 6 months I had tapered down to a quarter tablet, ~2mg. Around this time the sublingual film strips came out, and I was given a bunch of coupons to get them for free or like 5 dollars. Because of the lack of cost I figured I would stay on them longer and continue my slow taper. By the end of year 2 I was cutting the strips in 20 pieces, and the 1/20th piece still provided the same effect as the whole 8mg tablets I had in the beginning. When I lowered the dose each time, once any initial discomfort was over and I was 'normalized', the effects always felt the same and consistent, no matter the dose. Over the third year I had tapered down to a tiny 1/100th of a strip. Due to the difficulty in cutting the pieces so small (should have used volumetric dosing in retrospect) the size of the pieces would of course be slightly inconsistent, but I took extreme care cutting them so I would think the variation couldn't have been more than +/- 10%. During this time if I had accidentally taken one of the very slightly larger pieces the effect would be dramatic, to the point where I would be nodding, nauseated, and as high as ever before (with only maybe ~0.09mg max!!). I knew practically nothing about chemistry and pharmacology then so I never understood what was happening.

Now it seems that this increased sensitivity was caused by the ultra low dose use, but to the extent of whether it was the buprenorphine, the naloxone, or the combination is uncertain. I believe much research into this area is needed, but there is certainly something interesting going on.

EDIT: Seems everything could be explained from this paper.

https://www.ncbi.nlm.nih.gov/pubmed/18253501

9
[deleted] • Sep 22, 2018, 1:19 AM
[deleted]

1
jskafsjlflvdodmfe • Sep 22, 2018, 4:06 AM
Well I don't think I can say that, I didn't know what I was doing at the time, total accident. It was effective for me, completely eliminating my tolerance, and made getting off it a breeze. I can't say I recommend doing so as it can be difficult not to abuse it with such a low tolerance and I wouldn't recommend suboxone in general.

1
[deleted] • Sep 22, 2018, 5:31 AM
[deleted]

1
jskafsjlflvdodmfe • Sep 22, 2018, 6:29 AM
What does of d-amp were you using, and how long did it take for you to notice recovery/reduced tolerance?

1
darsinagol • Sep 22, 2018, 3:21 AM
Naloxone doesnt have much bioavailability when taken orally. The suboxone strips are for the buprenorphine. The naloxone is added so that if one tries to dissolve and shoot it up (or some other ROA) the naloxone will. eat the opiate to the receptor and kill the buprenorphine high before it starts.

1
jskafsjlflvdodmfe • Sep 22, 2018, 3:57 AM
The sublingual bioavailability is similar for both, which is how it was consumed, and at such low doses that is almost irrelevant. But I just found this paper which pretty much explains everything I experienced.

"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 show that with approximately 200-fold higher affinity than for the mu opioid receptor, naloxone binds a pentapeptide segment of the scaffolding protein filamin A, known to interact with the mu opioid receptor, to disrupt its chronic opioid-induced Gs coupling. Naloxone binding to filamin A is demonstrated by the absence of [(3)H]-and FITC-naloxone binding in the melanoma M2 cell line that does not contain filamin or MOR, contrasting with strong [(3)H]naloxone binding to its filamin A-transfected subclone A7 or to immunopurified filamin A. Naloxone binding to A7 cells was displaced by naltrexone but not by morphine, indicating a target distinct from opioid receptors and perhaps unique to naloxone and its analogs. The intracellular location of this binding site was confirmed by FITC-NLX binding in intact A7 cells. Overlapping peptide fragments from c-terminal filamin A revealed filamin A(2561-2565) as the binding site, and an alanine scan of this pentapeptide revealed an essential mid-point lysine. Finally, in organotypic striatal slice cultures, peptide fragments containing filamin A(2561-2565) abolished the prevention by 10 pM naloxone of both the chronic morphine-induced mu opioid receptor-Gs coupling and the downstream cAMP excitatory signal. These results establish filamin A as the target for ultra-low-dose opioid antagonists previously shown to enhance opioid analgesia and to prevent opioid tolerance and dependence."

https://www.ncbi.nlm.nih.gov/pubmed/18253501

1
iammyowndoctor • Sep 27, 2018, 9:39 AM
What you just read is correct, man. With suboxone for example, you can get high on it indefinitely without needing to increase the dose or losing strength of effect. All that increases is the speed at which it's metabolized.

I know this because I doing myself, and have been for the last 8 months or so.

1
Some90sScreenName • Nov 28, 2018, 8:00 PM
I have heard of this from a guy I know, and he said that the tolerance does not increase by much at all. It is quite scary to think about. He said he only upped his dose after about 3 months. The only problem is the fact that the withdrawal can last months after stopping it from withdrawals.

1
•iammyowndoctor • Nov 28, 2018, 8:48 PM
The only problem is the fact that the withdrawal can last months after stopping it from withdrawals.

I'm not sure this is really true. It's certainly never happened to me anyway. I mean you will get some symptoms that last a while, like diarrhea for one will continue for months typically, but besides that you certainly do not feel like shit for more than a week or so, IME.

Actually, went I detoxed from high dose benzos and opioids (and meth) last year, as soon as the bulk of the withdrawal was over, I started to feel really great, extremely optimistic, even though I was still technically feeling the withdrawal, my mood just improved so much that it didn't get me down.

So yeah, please don't buy into the idea that that will happen, it can really get you down, and sometimes depression can make withdrawal seem longer than it really is. I mean if you've really fucked up your life on dope, you probably will feel depressed after detoxed, I guess I did good that I didn't quite mess up my whole life, because this didn't happen to me. In fact, the dependency itself was really getting me down, I thought it would take years to taper down off of everything, so when I finally got thru with the bulk of the withdrawal, I felt like a million bucks not to have that weight on my shoulders anymore.

1
• •Some90sScreenName • Nov 29, 2018, 3:30 AM
I am not sure what your doses were, but withdrawal is not in any way as easy as you are making it sound. It is known that suboxone and methadone withdrawal are some of the longest withdrawals out there. Maybe you were in a clearer head space, but may addicts are not. I agree that the weight is gone, but that is only one problem. I am glad you are no longer dependent, but the way you make light of addiction is a bit concerning.

1
• • •iammyowndoctor • Nov 29, 2018, 12:31 PM
Haha. Lol, nah I'm dependent again. The difference is this time I don't feel bad about it though, but tolerance goes up at a snail's pace despite getting high pretty much everyday.

1
iammyowndoctor • Sep 27, 2018, 9:36 AM
During this time if I had accidentally taken one of the very slightly larger pieces the effect would be dramatic, to the point where I would be nodding, nauseated, and as high as ever before (with only maybe ~0.09mg max!!). I knew practically nothing about chemistry and pharmacology then so I never understood what was happening.

Are you saying this happened to you? Or it's what you expected would happen? I confused on whether you actually did get this effect from so small a dose. Very interesting indeed if so.

1
tristeza_xylella • Sep 21, 2018, 7:45 PM
LDN is a popular "experimental" treatment for MS. I havent seen any fellow MS-ers have side effects other than they wont be taking any opiate pain killers for dental work....

4
jskafsjlflvdodmfe • Sep 21, 2018, 8:27 PM
I believe you are referring to Naltrexone, not Naloxone.

9
tristeza_xylella • Sep 21, 2018, 8:37 PM
Yes. I'm sorry. This is the 2nd drug/healthcare mistake I've made on reddit in 12 hours time. Hanging head in shame:( tis hard to accept I am more patient (MS) than professional (RN) and drug nerd Guinea pig.

3
jskafsjlflvdodmfe • Sep 21, 2018, 8:54 PM
Oh its cool, I still mix the two up in casual conversation. I was mainly replying because I was curious if you were indeed talking about LDN using naloxone in place of naltrexone. I'm sure it could be used similarly, but I haven't seen any clinical usage. Though naloxone has a much faster onset, faster elimination, and different metabolites, maybe it wouldn't be as effective. Also, one of the two, I forgot which, has an active agonist metabolite, which could also play a role in therapeutic effects.

2
tristeza_xylella • Sep 23, 2018, 1:48 AM
Easier to call it "Narcan" and "LDN." But then we wouldn't be proper nerds.

1
recoverycat • Sep 22, 2018, 2:12 AM
Don't worry about it, I work in pharmacy and I have to think for a minute before remembering which is which.

2
dynamitemcnamara • Sep 21, 2018, 8:45 PM
Yeah it's naltrexone.

I'm interested to see if more studies will show that it really is efficacious in treating autoimmune diseases, the evidence so far seems promising.

2
AlkaliActivated • Sep 21, 2018, 8:44 PM
I believe they are functionally the same, and can work interchangeably in that protocol.

1
darsinagol • Sep 22, 2018, 3:19 AM
From my understanding the naloxone is a competitive antagonist to the opioid receptor. Which means they bind but don't activate. Would this still cause up regulation?

1
LacklusterIsomer • Sep 21, 2018, 8:43 PM
This is a really cool thought. Im just typing my minds thoughts so take that for what it is.

We know opiod addicts cant get through their withdrawal faster by taking naloxone. Yes it throwa you into withdrawal instantly but there is a specific term for it, its not actually upregulating or speeding up the process.

With that said, do we know what effect naloxone has when administered to someone who is not dependent on opiods or overdosing?

The body and mind always try to regulate, aka homeostasis, so any sustained change will result in some sort of effect I believe. We should consider how long Naloxone is active after administered while taking into account the change it makes on the sober brain.

If it is a dysphoric state that is prolonged indefinitely through continual persistant (or peak/slope) administration, I'd theorise even on a basic level, much like if you were tortured for some time, its action ceasing alone would feel 'better".

I think it would be a stretch to compare that to a high though. More a relief than anything.

I could be way off, just speaking my mind

4
freakorgeek • Sep 21, 2018, 9:17 PM
there is a specific term for it

Precipitated withdrawal.

5
LacklusterIsomer • Sep 21, 2018, 10:31 PM
Thanks man, yeah i was drawing a blank there.

1
iammyowndoctor • Sep 27, 2018, 9:42 AM
We know opiod addicts cant get through their withdrawal faster by taking naloxone. Yes it throwa you into withdrawal instantly but there is a specific term for it, its not actually upregulating or speeding up the process.

I believe it does actually. At least in instance of flumazenil with benzos anyway, look that med up on wikipedia it should be there. If it works there, I'd bet it would with opioids too.

Opioid antagonists have very little effect on someone not dependent on opioids. I've seen it myself in rehab. Two buddies of mine took the vivotrol shot, next day they're just eating lunch calmly as ever, as if nothing happened. I ask them, they say they feel the same.

1
Bluhah78 • Sep 30, 2018, 6:42 PM
It is clear you do not know how a receptor blockade of mu opioid works, your example is meaningless.

1
iammyowndoctor • Oct 1, 2018, 4:51 AM
I do man. Did you think "receptor blockade" meant "all receptors are totally off limits from any other kind of agonist/antagonist? That is not what it means dude. It only means that enough of them are blocked (at any one time) to prevent weaker binding drugs from having an overall effect on the body.

1
lulumeme • Jan 20, 2019, 10:58 AM
It's not comparable to a high, sure, but most people participating in low dose naltrexone, are typically recovering addicts, who are clean and use it for depression or pain, because it works better than standard antidepressants like SSRI's. The mild moodlift is more apparent and useful than the emotion numbing ssri effect

1
jskafsjlflvdodmfe • Sep 21, 2018, 8:44 PM
This is more or less how low dose naltrexone therapy works for PAWS, recovering opioid addicts, and probably other treatments as well. The nightly LDN dose causes a rebound effect the next day, with the effects of endogenous endorphins being much more pronounced through out the day, providing a modest relief. Over the long term, I assume that this can achieve significant up-regulation to the same level's as before opioid use and down-regulation occurred. I don't believe the up-regulation would be beyond 'normal' levels, to achieve a significant high when sober. Most likely, what you describe would lead to a day or two of a modest runners high type feeling, then homeostasis would normalize the person very quickly.

5
babunal • Sep 21, 2018, 8:21 PM
LDN has also been successfully used to treat ulcerative colitis.

4
whersmaihart • Sep 21, 2018, 8:37 PM
LDN is naltrexone, not naloxone

5
Some90sScreenName • Nov 28, 2018, 8:05 PM
The two are similar because it bonds to the mu opioid receptors. That can have an impact on digestion and how the intestines work.

1
Dctr_K • Sep 21, 2018, 6:25 PM
Interesting theory, not sure if thats the case tho. Maybe some one will chime in with some info

3
EnduringInsanity • Sep 22, 2018, 2:11 AM
So naloxone does have some effects when administered to a non tolerant individual not euphoric nor dysphoric but mostly just a sedative with some other effects. https://psychonautwiki.org/wiki/Naloxone Because of the emotion suppression it makes me believe it could lead to anxiety during widthdrawl and maybe some benzo like widthdrawl effects?

1
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1
Giboras • Sep 26, 2018, 3:51 PM
Naloxone doesnt just antagonize the mu-opioid receptor, but the kappa as well (not as strong, but still).
Kappa-Opioid receptor activaton is associated with dysphoria and anxiety.
Antagonizing them with Naloxone will most likely cause them to upregulate.
When discontinuing the Naloxone, more Kappa Receptors could be presnt and could lead to dysphoria. (until homeostasis).
The possible heightened mu-opioid receptor count cound cancel that out.

1
rogueMD39 • Sep 26, 2018, 11:38 PM
This is a common phenomenon in patients that take specifically low doses of naltrexone or naloxone. It doesn't seem to happen often in patients at the normal dose range. I'm not quite sure why

1
iammyowndoctor • Sep 27, 2018, 9:44 AM
IME, opioid antagonists have basically no effect on people not dependent on agonists. I saw two buddies in rehab get on vivotrol, they literally did not change one bit afterwards, and said they felt the same as well.

I'm not sure why this is but I want to get to the bottom of it too. Great question btw, thought of it many times myself as you can see.

1
kratonian • Oct 17, 2018, 7:16 AM
i have been dependant on opiates on and off for years, after trying all kinds of meds from a-z from my TRD / MDD



Opiates, particularly full agonists like heroin, were the only drugs that relieved all my symptoms of depression and anxiety. Anyways, after mutliple failed detox attempts, many different opiates/opioids, I relapsed on heroin and cocaine and was speeballing daily for a few months and went through large amounts, felt great though. Finally after years of contemplating, I just got on sub (zubsolv). They started me on 5.7mg 3x a day, which seems like a lot, but im on day 2 and feel like absolute crap.



I just want the antidepressant effect I got from full agonists, and I just want to be functional again, I know this will take some time, esp. because of the cocaine abuse. But what can I change/add to this regimen to make it more effective at combating my depression/upregulating opiate receptors?



I have access to LDN/ULDN but I doubt thats of any use here

1
rekaikutan • Sep 21, 2018, 7:28 PM
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