Ray Peat on Naltrexone

[Artemisia]

The link below is a website that you can search Ray Peat interviews, set to display "naltrexone"

it has several hits, where he addresses questions related to naltrexone in interviews

Two points here:

1. Ray Peat said that 2 or 3 days of low dose naltrexone or naloxone can be enough to break up a pattern with CFS. He also says 4 mg is a large dose and some people only need less than 1 mg -- sometimes even 0.001 of a milligram.

Has anyone had permanent improvement taking it for a short time, or off and on for short periods?

2. He mentions the established fact that naltrexone works by lowering endorphins which are endogenous opiates and, he says, an emergency stress response to turn off excitation.

I knew naltrexone lowered endorphins, but the mainstream view is that endorphins are good. Peat often held an opposing view on many commonly perceived beneficial substances like estrogen and serotonin as well.

But if the mainstream is correct and endorphins are beneficial, how could naltrexone's mechanism of action make sense for pwME?

It makes sense with opioid abuse / addiction but not so much ME/CFS.

Unless... ME/CFS could be considered an ENDOGENOUS opioid addiction!

Are we "addicted" to internally produced opioids such as endorphins (relying on a subpar energy production that leads to high endorphin levels)?

I believe that's what Peat is saying in the first search result.

bonus point -
he seems to prefer naloxone, saying it's essentially identical to naltrexone but is oil soluble. dissolving naloxone in oil would be preferable IMO to water solutions because the oil solution would last longer, I bet.

https://bioenergetic.life/?q=naltrexone

 

[bad1080]

naltrexone is a glia cell modulator which is the main factor for PwME imo

I knew naltrexone lowered endorphins, but the mainstream view is that endorphins are good.

the mode of action here is naltrexone blocks the receptor which has the body produce more endorphins. so you have a period of less endorphin action at the receptor (often perceived as anhedonia) followed by a period of more action (perceived as uplift or more energy).

the oil solution would last longer, I bet.

i use my self-made naltrexone solution (with distilled water) for about a month without issues

Has anyone had permanent improvement taking it for a short time

i have not heard of such a thing but i guess it's not impossible if you catch it early and start treatment right away. it's just most of us had me-cfs for too long so the glia cells snap back into their activated state too easily.

another mode of action is on the mu opioid receptors with are also located in the intestinal tract, so it has a regulating effect on the digestion (but it can lead to constipation in some).

 

[Artemisia]

the mode of action here is naltrexone blocks the receptor which has the body produce more endorphins. so you have a period of less endorphin action at the receptor (often perceived as anhedonia) followed by a period of more action (perceived as uplift).

sort of sounds like the SSRI theory. block the receptor to make the body produce more. that doesn't seem like a healthy thing long term to me.

but since peat believed endorphins to be a stress response, i wonder how his theory would fit in with the resulting INCREASED endorphins from naltrexone.

this article says the dose needs to be 1-5 mg to have the glia cell modulator effect: so i guess peat's ultra low doses wouldn't achieve that.

When used in doses of 1 to 5 mg it acts as a glial modulator with a neuroprotective effect via inhibition of microglial activation. It binds to Toll-like receptor 4 and acts as an antagonist, therefore inhibiting the downstream cellular signaling pathways that ultimately lead to pro-inflammatory cytokines, therefore reducing inflammatory response. Its other mode of action involves transient opioid receptor blockade ensuing from low-dose use which upregulates opioid signaling resulting in increased levels of endogenous opioid production, known as opioid rebound effect. Low dose naltrexone has gained popularity as an off-label treatment of several autoimmune diseases including multiple sclerosis and inflammatory bowel disease, as well as chronic pain disorders including fibromyalgia, complex regional pain syndrome, and diabetic neuropathy. Low-dose naltrexone (LDN) may also have utility in improving mood disorders and the potential to enhance the quality of life.

 

[bad1080]

the dose needs to be 1-5 mg

it is highly individual, those are just the doses they investigated. if you look at the forums you can see people have positive effects from all kinds of doses even ultra low dose naltrexone like you said (or as high as 6, 9 or even 12mg) but by what mode of action would be hard to determine i guess.

that doesn't seem like a healthy thing long term to me.

i mean neither is living with me-cfs, whatever helps i guess and the side-effects profile of LDN is well known at this point.

edit: there is an naltrexone isomer which doesn't fit into the opioid receptor but it is not FDA approved. that would be interesting to study in regards to efficacy and side-effects. jarred younger talks about it in one of his videos but i forgot which one: https://www.youtube.com/@youngerlab/search?query=naltrexone

 

[Artemisia]

Here he suggests that there is no harm in taking it long term, but thinks that an apporpriate diet and other measures he recommends like thyroid and progesterone, are preferable.

"Any problem w/ long term use?
"No, but I usually see good results in 2 or 3 days. The basic treatment is a good diet and thyroid supplement as needed. The naltrexone is a good thing to try once in a while. If it makes you feel better then it probably was breaking up a pattern."

If only Peat's appropriate diet and thyroid were enough to cure me and everyone with ME. Goodness knows I've tried.

https://bioenergetic.life/clips/8442a?t=2554&c=56

 

[Artemisia]

i mean neither is living with me-cfs, whatever helps i guess and the side-effects profile of LDN is well known at this point.

true, i just haven't gotten it to work for me, though i haven't given it a long trial of months. i'm just wary of making things worse. it's a dilemma bc i need to improve my baseline to survive at this point but so many things make me worse that help others. so i'm cautious but i need to do something.

 

[bad1080]

true, i just haven't gotten it to work for me, though i haven't given it a long trial of months. i'm just wary of making things worse. it's a dilemma bc i need to improve my baseline to survive at this point but so many things make me worse that help others. so i'm cautious but i need to do something.

yeah the hypersensitivity to medications makes this tough for us. all i can recommend is to start low and go slow (i started with 0.5mg and even that was too much for me, 0.25mg worked much better for me). having a sloution with which you can adjust the dose on the fly (without ordering new capsules) makes it much easier. experimenting with >when< you take it is also a good idea (some get tired others active - i had both).

i added this to an answer up there but let me repeat it here: there is an naltrexone isomer which doesn't fit into the opioid receptor but it is not FDA approved (and i forgot the name). that would be interesting to study in regards to efficacy and side-effects. jarred younger talks about it in one of his videos but i forgot which one: https://www.youtube.com/@youngerlab/search?query=naltrexone

 

[cfs since 1998]

The link below is a website that you can search Ray Peat interviews, set to display "naltrexone"

it has several hits, where he addresses questions related to naltrexone in interviews

Two points here:

1. Ray Peat said that 2 or 3 days of low dose naltrexone or naloxone can be enough to break up a pattern with CFS. He also says 4 mg is a large dose and some people only need less than 1 mg -- sometimes even 0.001 of a milligram.

Has anyone had permanent improvement taking it for a short time, or off and on for short periods?

2. He mentions the established fact that naltrexone works by lowering endorphins which are endogenous opiates and, he says, an emergency stress response to turn off excitation.

I knew naltrexone lowered endorphins, but the mainstream view is that endorphins are good. Peat often held an opposing view on many commonly perceived beneficial substances like estrogen and serotonin as well.

But if the mainstream is correct and endorphins are beneficial, how could naltrexone's mechanism of action make sense for pwME?

It makes sense with opioid abuse / addiction but not so much ME/CFS.

Unless... ME/CFS could be considered an ENDOGENOUS opioid addiction!

Are we "addicted" to internally produced opioids such as endorphins (relying on a subpar energy production that leads to high endorphin levels)?

I believe that's what Peat is saying in the first search result.

bonus point -
he seems to prefer naloxone, saying it's essentially identical to naltrexone but is oil soluble. dissolving naloxone in oil would be preferable IMO to water solutions because the oil solution would last longer, I bet.

https://bioenergetic.life/?q=naltrexone

Never heard of Ray Peat. Sounds like a quack. Says CFS is caused by toxins in beans? Okay. Most of what you wrote above is wrong. The idea of LDN is that temporarily blocking the receptors leads to INCREASE in endorphins.

 

[Artemisia]

Says CFS is caused by toxins in beans? Okay.

that's a big misrepresentation.
he's said that beans are one type of food that can cause the intestinal imbalance that can lead to cfs. it's not just beans though. his theory hinges on endotoxins in the intestine.
if you'd never heard of him before today you're not gonna be able to make an accurate snap judgment of his work

anyway naltrexone does lower endorphins until the receptors rebound, which could be why he suggests short term usage

 

[Artemisia]

anyway the whole mechanism of action of SSRIs, with receptors being shut down to make the body produce more, was revealed to not be what they claimed for decades, which was a not-so-hidden secret in psychiatry

doesn't hurt to ask questions about this. medical science is far from right about everything. anti-authoritarianism is the way to go

 

[Rufous McKinney]

Naltrexone increases 1) opioid receptors themselves ; and 2) increases endorphins as a result.

I thought.

I take 3.5 mgs around midnight. If I wake up around, say, 2 or 3 am for some reason, I typically notice I have a sort of bad headache. I then go back to sleep and do not have a headache in the AM (per se).

 

[Rufous McKinney]

he seems to prefer naloxone, saying it's essentially identical to naltrexone but is oil soluble. dissolving naloxone in oil would be preferable IMO to water solutions because the oil solution would last longer, I bet.

Dr. Chris Armstrong (I think) has a video on another form of naltrexone he thinks may work better for us.

I'd have to go dig that up.

 

[Rufous McKinney]

ort of sounds like the SSRI theory. block the receptor to make the body produce more. that doesn't seem like a healthy thing long term to me.

I'm pretty sure I"ve used ldN. for at least ten years. Same dose, 3.5 mgs.

 

[Rufous McKinney]

jarred younger talks about it in one of his videos but i forgot which one: https://www.youtube.com/@youngerlab/search?query=naltrexone

I meant Jarred Younger. (not Dr. Armstrong...I mix those two up all the time)

 

[Rufous McKinney]

progesterone

I used bio-identiical progesterone cream: from around the age of 48- 64. I can't recall exactly when I stopped using it. I always used less than the recommended dose per Dr. Lee.

I found it very helpful for perimenopause symptoms and it likely helped me out in other ways because I only got the far worse ME after I had stopped it. (not blaming that).

Never heard of Ray Peat. Sounds like a quack

I do not think his take on this is correct.

My diet is pretty excellent. I stopped eating the standard American Diet at the age of 16 and it was 1969.

I"ve rarely taken a pharmaceutical in this ENTIRE life. I won't take a Tylenol.

 

[Rufous McKinney]

was revealed to not be what they claimed for decades

I checked, and that is still the reported Mechanism of Action. The SSRI blocks receptors leading to an increase d level of serotonin.

The issue I think, is that DOES NOT necessarily have anything to do with WHY you're depressed. The reason you thought you were taking the pill for.

 

[JES]

Naltrexone in low dose seems like a relatively safe treatment that has been used off-label to treat ME/CFS for quite a while now. I have not heard about any massive recovery stories from it where a moderate or severe patient would suddenly become well.

SSRI's do block serotonin reuptake, however, it is also well known that the effect of SSRI's typically doesn't kick in until after two to even four weeks, whereas the effect on serotonin should be established much quicker as most SSRI's have a half-life of around a day, meaning it doesn't take weeks to build up to a steady-state dose.

It could very well be that both naltrexone and SSRI's achieve their effect via "something else" than the established primary mechanism.

 

[Wishful]

Has anyone had permanent improvement taking it for a short time, or off and on for short periods?

I had permanent improvement (stopped ME-caused aches), but it took one or two years to become permanent. Also, it had no effect on my other ME symptoms. LDN seems to work via different mechanisms in different individuals.

 

[Rufous McKinney]

SSRI's do block serotonin reuptake, however, it is also well known that the effect of SSRI's typically doesn't kick in until after two to even four weeks,

I lasted two days on Zoloft. It was like a nightmare, for 48 hours and then I was sick for weeks after.

How's that even possible?

 

[Artemisia]

It could very well be that both naltrexone and SSRI's achieve their effect via "something else" than the established primary mechanism.

yes this is what i was thinking

I had permanent improvement (stopped ME-caused aches), but it took one or two years to become permanent. Also, it had no effect on my other ME symptoms. LDN

very interesting