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dextronaltrexone

neuroprotection microglia anti inflammatory naltrexone

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#1 StevesPetRat

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Posted 10 July 2014 - 02:20 PM


Sure, you could screw around with the opioid receptors but why not go straight for the microglia? Therapeutic doses run around a few mg a day. Can't imagine synthesis would cost that much.

http://www.ncbi.nlm....les/PMC2891387/

More recently, naltrexone (and its shorter acting cousin, naloxone) has also been found to attenuate the production of proinflammatory cytokines and neurotoxic superoxides via suppressive effects on central nervous system microglia cells [2327]. The reduction of proinflammatory cytokines can be achieved with ultra low doses, and can reduce thermal hyperalgesia in a rat model [28]. The effect is not due to opioid receptor activity, as the opioid nonactive isomers dextro-naloxone and dextro-naltrexone also exhibit neuroprotective benefits; it is instead potentially mediated by activity on toll-like receptor 4 [29,30].



#2 macropsia

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Posted 10 July 2014 - 04:17 PM

I've been saying this for years... Naloxone also looks like a great option for exploring these concepts, but the ldn-grassroots movement is unfortunately very hung up on the metenkephalin aspect.
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#3 Geoffrey

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Posted 21 November 2014 - 02:58 PM

Does it really matter that the Low Dose Naltrexone community is "hung up" on met-enkephalin? That side of the "therapy" is probably just the feel-good factor that reinforces use of the drug, while its method of action in inflammatory disease is as a microglial modulator. At least that's the theory of this Rheumatology paper on it from earlier this year, drawing on the paper cited above: "The Use of Low-Dose Naltroxen as a Novel Anti-Inflammatory Treatment for Chronic Pain" http://link.springer...2/fulltext.html .

It's extremely easy and pretty cheap to get hold of basic naltrexone (mine arrived 3 days after ordering) and to dilute it yourself. I dissolved 50mg tablet in 16 measures of water to make 3mg per measure -- or you could use 11 measures of water for 4.5mg per measure. Solution must be refrigerated.

The endorphin rebound is not necessarily a bad thing (if that's what's happening), so I don't see any need to synth dextro-naltrexone just to experiment. I guess if you have trouble sleeping due to endorphin suppression at night (following bedtime dose), then dextro would be useful, and it certainly should be investigated for its potential as a disease modifying agent. But for nootropic effects, other than as a kind of anti-oxidant, I'd have thought the endorphin rebound of levo-naltrexone (the one that's available) would actually be a useful effect.

After four bedtime doses of 3mg, I notice the following so far: It suppresses coffee craving (I drank far less coffee than I usually do); I don't feel very hungry (which might or might not be a useful effect); it so far abolishes any afternoon fatigue I usually have (since the endorphin rebound seems strongest in the afternoon following a night-time dose); I feel slightly euphoric towards the end of the afternoon, so far on all four days. It feels a little as if I'm on armodafinil, but without the "forced" feeling modafinil sometimes gives me. Possible negatives: it seems to irritate my urinary tract, particularly early morning; I don't feel that great when I wake up.

I may need to lower the dose, if the opioid receptor blockade is lasting too long (I guess this is where having access to dextro-naltrexone could be a useful comparator). I should declare that I also have a mild chronic inflammation (has been medically investigated) that I'm trying to get rid of, so my motivation is not entirely nootropic. I don't know whether the endorphin rebound is masking the inflammation / myalgia or whether the microglial modification is kicking in, but so far so good (early days / placebo). I aim to have blood work done in early January to see if the anti-inflammatory effects are real (I have raised ESR and CRP).

Edited by Geoffrey, 21 November 2014 - 03:06 PM.

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#4 StevesPetRat

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Posted 21 November 2014 - 08:29 PM

The endorphin rebound is not necessarily a bad thing (if that's what's happening), so I don't see any need to synth dextro-naltrexone just to experiment...
I may need to lower the dose, if the opioid receptor blockade is lasting too long (I guess this is where having access to dextro-naltrexone could be a useful comparator). I should declare that I also have a mild chronic inflammation (has been medically investigated) that I'm trying to get rid of, so my motivation is not entirely nootropic. I don't know whether the endorphin rebound is masking the inflammation / myalgia or whether the microglial modification is kicking in, but so far so good (early days / placebo).

Glad to hear another potential LDN success story! I should've added to the original post my other thought on the matter, which is that you don't want 24 hour endorphin blockade, but you do want 24 hour neuroprotection. So I would envision a traditional LDN dose at night plus 2-4 mg dextroN 2-3x during the day as being the "ideal" treatment regime. As somebody with an extensive family history of autoimmune disease, my interest in the matter is not purely academic...

Also, if one were to buy pure naltrexone powder from a compounding pharmacy, it may be possible to stereo-separate the isomers at home using the right chiral reagents. I never took OChem, though, so I personally have no clue how to do that safely.

#5 Gorthaur

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Posted 22 November 2014 - 06:18 AM

I'm not quite clear what effect you expect from dextronaltrexone? It's hard to keep track of how many different reasons people use it for. I have used both high and low dose naltrexone, and I've never found the dysphoria and insomnia to be worth the endorphin boost. 



#6 StevesPetRat

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Posted 22 November 2014 - 07:00 PM

I'm not quite clear what effect you expect from dextronaltrexone? It's hard to keep track of how many different reasons people use it for. I have used both high and low dose naltrexone, and I've never found the dysphoria and insomnia to be worth the endorphin boost.

Well, that's exactly the point -- we can get the anti-inflammatory benefits, neurological and otherwise, without the endorphin blockade (there will be no endorphin rebound, either, but you can use e.g. DPA for that). Furthermore, it can be dosed multiple times daily rather than requiring it to wear off most of the day. DextroN acts on TLR-4 which is the lipopolysaccharide (LPS) receptor. If I have read the research correctly, enkephalin antagonism UPregulates TLR-4, so you've got "one foot on the brakes and one on the gas", at least until your own enkephalin production increases to compensate. It may not have the "immune-boosting" benefits for AIDS and cancer patients, but it is likely to be of even greater benefit in autoimmune and neuroinflammatory conditions (such as fibromyalgia and CFS).

Another way to effect a similar benefit would be to destroy all the gram negative bacteria in your body, except the very few species that release TLR-4 antagonists rather than agonists as their endotoxins. However, one can stomach only so much xylitol and lactoferrin in a day.

It seems this would be a very cheap, potent medicine, and I'm trying to generate some more interest. Hell, a pharmaceutical company could even acquire a "new-use" patent on it!

#7 macropsia

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Posted 22 November 2014 - 10:23 PM

The prospect of enantomerically pure naltrexone and naloxone excite me greatly. Exploration of their usefulness is well within the ability of grassroots experimentation - RCTs would be nice, but I would honestly be almost more satisfied with a handful of anecdotes from CFS, FM, Crohn's, MS, Aspergers and autism patients. Seeing as its safety is well established , I think it would be an easy sell. I've a hunch that levo-naloxone and and a higher dose of dextronaltrexone would be superior in regards to both mechanisms of LDNs action - shorter opiate blockade and more TLR antagonism. I will see if I can find anyone willing to produce d-naltrexone.

#8 StevesPetRat

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Posted 23 November 2014 - 04:44 AM

I will see if I can find anyone willing to produce d-naltrexone.

That would be amazing. Please keep us appraised!



#9 FW900

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Posted 23 November 2014 - 07:47 AM

 

I will see if I can find anyone willing to produce d-naltrexone.

That would be amazing. Please keep us appraised!

 

 

I'm down for a group buy (as a member, not hosting it) assuming he gets a favorable price quote. Regular naltrexone is pretty damn expensive, even on AllDayChemist.



#10 Hip

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Posted 06 December 2014 - 06:30 PM

I'd be interested in a group buy of dextro-naltrexone as well.



#11 deetown

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Posted 30 April 2015 - 10:50 PM

I'm in for a group buy



#12 lourdaud

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Posted 01 May 2015 - 09:56 AM

I'm in.


Edited by lourdaud, 01 May 2015 - 09:56 AM.


#13 DjKrush86

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Posted 12 June 2015 - 12:15 AM

I have been looking all over for dextro-naltrexone, does someone here know where to buy it?


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#14 Steve Hull

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Posted 30 June 2017 - 06:33 PM

So interesting -- I've been researching NDMAr & TLR4 antagonists for maybe a year now. Stumbled on dextronaloxone on wikipedia a couple months ago and immediately thought "well that sounds like something we should try for FM." Considering longer half-life of dextro-naltrexone, that sounds even better.

 

 

I've a hunch that levo-naloxone and and a higher dose of dextronaltrexone would be superior in regards to both mechanisms of LDNs action

 

I 100% agree with this hunch.

 

 

My wife suffers from RA & FM and sometimes has uncontrollable pain "episodes" (as I call them) that can last anywhere from a number of hours to an entire week.

 

It strikes me that drugs that block activation of microglia and astrocytes (both are types of glia that when "activated" release inflammatory cytokines, including TNFa, which is targeted by DMARDs) would be useful for both RA & FM.

 

tl;dr -- if anyone here is setting up or has set up a group buy I want in please @FW900 @Hip @deetown @lourdaud



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#15 Infinite1

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Posted 25 July 2018 - 03:28 PM

I'm just running across this, and would be interested in finding a source for dextro-naltrexone. Anything ever come of this? 







Also tagged with one or more of these keywords: neuroprotection, microglia, anti inflammatory, naltrexone

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