Allopregnanolone

[Shadow]

I have a very weird symptom wich I saw being reported among some people with PSSD and SSRI discontinuation in general. Lack of skin sensitivity. I dont know if people with PFS/Post-acuttane experienced this too. But I was very intrigued about how could be doing it, until today.

I found this https://books.google.com.br/books?id=D1fOTC6CP3kC&pg=PA70&lpg=PA70 wich make a lot of sense!

My lack of sensitivity started after the tapering of the reinstated drug! Let me explain better, I was on ssri than I got out, I had pssd and other symptoms, them my dr wanted me to reinstate the drugs, them the sensitivity problems appeared and worsened while tapering the drug(I experienced a week of full recovery and at the end of tapering a increase in libido and decrease of sensitivity).

What I know is that on short term SSRIs boosts the production of ALLO, and lowers it on long term, they do it trhough 3alpha-HSD.

Reading that, I learned something that I didnt knew, finasteride lowers ALLO by a lot and so does Isotretinoin! The lack of ALLO can explain a lot of our symptoms.

This made me wonder, how does ALLO fits in [mention]gbolduev[/mention] theory?

 

[expendable]

I've read about this before, but now I'm really interested. Shadow, do you remember the case that Ghost (I think) mentioned once, about the woman who was cured of all pssd like symptoms during pregnancy? Apparently, ALLO increases throughout pregnancy. I just read a few studies where, to lower the amount of ALLO in a test group (usually rats), the researchers literally just gave them finasteride. Damn. Since it's synthesized from prog, there could definitely be a connection...

From wiki: Increased levels of allopregnanolone can produce paradoxical effects, including negative mood, anxiety, irritability, and aggression.[32][33][34] This appears to be because allopregnanolone possesses biphasic, U-shaped actions at the GABAA receptor – moderate level increases (in the range of 1.5–2 nM/L total allopregnanolone, which are approximately equivalent to luteal phase levels) inhibit the activity of the receptor, while lower and higher concentration increases stimulate it.[32][33] This seems to be a common effect of many GABAA receptor positive allosteric modulators.[29][34] In accordance, acute administration of low doses of micronized progesterone (which reliably elevates allopregnanolone levels), have been found to have negative effects on mood, while higher doses have a neutral effect.[35]

EDIT: Saw the "Accutane recoveries w/ finasteride" thread again. Possible connection...?

 

[Jaxx]

I've read about this before, but now I'm really interested. Shadow, do you remember the case that Ghost (I think) mentioned once, about the woman who was cured of all pssd like symptoms during pregnancy? Apparently, ALLO increases throughout pregnancy. I just read a few studies where, to lower the amount of ALLO in a test group (usually rats), the researchers literally just gave them finasteride. Damn. Since it's synthesized from prog, there could definitely be a connection...

From wiki: Increased levels of allopregnanolone can produce paradoxical effects, including negative mood, anxiety, irritability, and aggression.[32][33][34] This appears to be because allopregnanolone possesses biphasic, U-shaped actions at the GABAA receptor – moderate level increases (in the range of 1.5–2 nM/L total allopregnanolone, which are approximately equivalent to luteal phase levels) inhibit the activity of the receptor, while lower and higher concentration increases stimulate it.[32][33] This seems to be a common effect of many GABAA receptor positive allosteric modulators.[29][34] In accordance, acute administration of low doses of micronized progesterone (which reliably elevates allopregnanolone levels), have been found to have negative effects on mood, while higher doses have a neutral effect.[35]

EDIT: Saw the "Accutane recoveries w/ finasteride" thread again. Possible connection...?

This was the original post http://area-1255.forumotion.info/t58-pssd-what-has-helped-me

Mentioned in http://www.pssdforum.com/viewtopic.php?f=5&t=1405&p=14345&hilit=Jaxx#p14345

 

[Shadow]

[mention]expendable[/mention] another interesting event was pete's recovery using low dose SSRI. Which can be explained by this: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670606/

The article shows that SSRIs antidepressant effects could be the work of neurosteroids(Allo mainly) and not due to serotonin reuptake inhibition.

 

[Jaxx]

Pete’s recovery was indeed interesting, but it could also be directly related to progesterone. What is also interesting is that he didnt build it up to “ snap back” but more created momentum by dosing every other 2-3 days. Some stories are almost as if we need to reboot an engine with small but frequent boosts

 

[expendable]

@expendable another interesting event was pete's recovery using low dose SSRI. Which can be explained by this: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670606/

The article shows that SSRIs antidepressant effects could be the work of neurosteroids(Allo mainly) and not due to serotonin reuptake inhibition.

Fluoxetine increased biosynthesis of Allo, then? And that's why Pete recovered? But how does finasteride lead to the recovery of accutane users when it does the opposite? If we have high prog, shouldn't we have high allo as well?

Pete’s recovery was indeed interesting, but it could also be directly related to progesterone. What is also interesting is that he didnt build it up to “ snap back” but more created momentum by dosing every other 2-3 days. Some stories are almost as if we need to reboot an engine with small but frequent boosts

I feel more and more like this is the case. Imagine cycling licorice root, 450mg/day on weekends, plus 10mg RU over 3 days every 2 weeks (friday/sat/sun).

 

[Shadow]

Very good question [mention]expendable[/mention], maybe the sudden increase of Allo kicked the engine back.
Maybe [mention]gbolduev[/mention] and [mention]mattyb[/mention] could shed some light about this.

 

[expendable]

More research on this because I'm bored at 2 am.

http://www.propeciahelp.com/forum/download/file.php?id=21&sid=58b5edbec465583ce33fe780063e7171

5α-Dihydroprogesterone (5α-DHP), also known as allopregnanedione,[1] as well as 5α-pregnane-3,20-dione, is an endogenous progestogen and neurosteroid that is synthesized from progesterone.[2][3] It is also an intermediate in the synthesis of allopregnanolone and isopregnanolone from progesterone.

Well, we know this. So fucking close

 

[wuf]

Interesting, I just wanted to report about a PFS suffer (a friend of mine on the italian comunity) who is using 10mg allopregnanolone and 10mg Dhea and he claims to have restored his sexual functions..
I am just wondering if he can ever stop this integration and what will happen and if he can get a possible shut down.

 

[expendable]

Interesting, I just wanted to report about a PFS suffer (a friend of mine on the italian comunity) who is using 10mg allopregnanolone and 10mg Dhea and he claims to have restored his sexual functions..
I am just wondering if he can ever stop this integration and what will happen and if he can get a possible shut down.

Keep us updated on that guy. In the meantime, I found an article that says that rats treated with 5aDHP had increased FSH on day 3 and rats treated with 3a5a-THP (allo) had increased FSH and LH on days 2 and 3. Interesting. Also interesting is that a lot of charts out there are kind of meh, missing a lot of stuff. I've been compiling a complete steroid hormone chart in my spare time because I just can't find a complete one. This one http://www.genome.jp/kegg-bin/show_pathway?hsa00140+1109 is pretty thorough, but still missing stuff. I'm particularly interested in the pathway from progesterone, to 3a/5a/3b/5b DHP, and then 5aDHP to allopregnanedione -> allopregnanolone (also interesting is 5bdhp->epipregnanolone, pregnanolone->pregnanediol). Also important are the aldosterone and cortisol->cortisone pathways gbold mentionedl, but I haven't done heavy research into those yet :lol:

Some random info:

3α-DHP has also been found to inhibit the secretion of follicle-stimulating hormone (FSH) from the rat pituitary gland, demonstrating possible antigonadotropic properties.[1] Unlike the case of most other inhibitory neurosteroids, 3α-DHP production is not blocked by 5α-reductase inhibitors like finasteride.[1]
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Various antidepressants, including the SSRIs fluoxetine, fluvoxamine, sertraline, and paroxetine, the SNRI venlafaxine, and mirtazapine, have been found to activate certain 3α-HSD enzymes, resulting in a selective facilitation of 5α-dihydroprogesterone conversion into allopregnanolone. (I think this was mentioned further up in the thread)
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2858310/ States that estrogen is necessary for 3a5a-THP (allo) to have an effect- so low estrogen = no improvement even with + more allo? there's a synthetic allopregnanolone called ganaxolone in trial, since oral allopregnanolone has a very short half life