PFS caused by Neurosteroid pathway interruption?

Hey man - thanks so much for this response.

Very interested to see that your symptoms are the same as mine (feeling wired and overstimulated all the time etc), I haven’t come across that many people with similar such symptoms. The best way I could describe it to a non-sufferer would be like an extreme caffeine overdose, but that doesn’t really do it justice.

I haven’t made a habit of Benzo’s - my go to is now CBC and meditation to help relax the mind, which definitely works to a certain extent. Although as you say, CBD is very expensive!

I did also previously find nicotine quite therapeutic for my symptoms. I discovered this by accident when using a high concentration vaping device (Juul). Again, I have seen that nicotine is a GABA A agonist so makes some sort of sense. I quit vaping though due to concerns on health impact.

Thanks for the other treatment ideas you mentioned. Would love to ask a couple of questions if possible:

  1. Via what mechanism does HCG repair neurosteroidogenesis? From what I can see, it replicates Pituitary signalling which causes the Testes to increase endogenous Testosterone production. How does this link back to AP synthesis in the cerebrospinal fluid? How efficacious was this treatment vs Fluoxetine for you?

  2. Similarly, how do HDAC inhibitors fit into this puzzle? If you could share the food sources of HDAC inhibitors, that would be great.

  3. How has TRT impacted your recovery and what supplements have you used for Traumatic Brain injury? What effect have they had?

Did Leo offer any guidance as to whether there are any Doctors that specialise in any of this? I have previously visited a Neurologist with my symptoms who was unable to diagnose anything, although I am considering returning to him armed with this new information.

Thanks again!

All good man. I just want to make it clear that I am simply sharing what I am doing and my experience, everyone is different so don’t blindly copy me without doing your own research and due diligence first. I’m just aware that some people can be very sensitive and I don’t want to make anyones situation worse with my advice. I am also no expert, I am just someone like you who is trying to figure this shit out through trial and error.

To answer your questions.

1. HCG: I do not have a scientific reference to share to support my previous statement on HCGs ability to repair neurosteroidogenesis. This was simply recommended to me from Leo in a private consultation. I also had this recommended to me by Dave Lee (look him up on the TRT and Hormone Optimisation Channel) who has worked with PFSers before. Dave and Leo both said that HCG should be the first point of call for treatment to restart the HPTA, Steroid Acute Regulatory Protein (StAR) and neurosteroidogenesis. If you want a scientific explanation, you may need to pay for a consult with Leo, I’m sure he will explain the science and supply a massive list of papers to support his claims. I personally believe it has to do with HCG stimulating the testies to produce the prohormones to all the neurosteroids, but I’m not certain on this and don’t want to make any claims. Here’s a good anecdote to check out.

2. HDAC Inhibitors: Leo said, the changes due to finasteride can only logically be due to epigenetic changes. By manipulating HDACs you make it easier for your body to reverse the epigenetic changes and make your epigenetics reflect your current environment. One of the ways epigenetic changes occurs is through Histone Deacetylation. Per wikipedia: acetylation of histones is known to increase the expression of genes through transcription activation. Deacetylation performed by HDAC molecules has the opposite effect. This leads to decreased levels of gene expression and is known as gene silencing. Therefore by optimising our use of HDAC inhibitors (Histone Deacetylation Inhibitors) we help our body increase expression of genes and help our epigenetics to reflect our current environment. Leo advised me to do this in our consult and he briefly explains it in the following video.

Leo recommends sodium valproate, sodium butyrate and Tributryin (sodium / magnesium / calcium butyrate) as HDAC inhibitors. I personally will not be taking these compounds and strongly advise you to avoid them as well, just take a look what happened to Papasmurf after experimenting with Sodium Butyrate:

Personally, I will be following @headsup’s advice, optimise my diet to inhibit HDACs, reduce oxidative stress, and inflammation. Foods to focus on for inhibiting HDACs include:

  • Sulforaphane. Broccoli Sprouts.
  • Cooked and then cooled white potatoes. Cold potatoes are the best way to increase Butyrate in the gut.
  • Chamomile Tea.
  • Celery.
  • Garlic.
  • Ashwagandha.
  • NAC.

3. TRT & TBI: I have literally only just started TRT this week. Although my testosterone status is good, 900-1100 ng/dl, I exhibit all the classic signs of testosterone deficiency. The normal reference range in my opinion is based upon a sick, diseased, unoptimised, obese population and does not take into account receptor sensitivity to androgens. The “normal” reference range has been reduced multiple times over the past few decades and does not represent human physiology and is a representation that the average human is old and sick (IN MY OPINION). I also believe PFS induces a degree of receptor insensitivity / resistance, so more hormone is required to saturate the receptors to elicit the same effect. I am treating the symptoms, not a number on a piece of paper. Leo actually advised against TRT use, unless I was using HCG, as it will negatively effect neurosteroidogenesis. But this is why I am supplementing with progesterone to hopefully mitigate this negative outcome caused by TRT.

Regarding TBI. I suggest you check out the Reddit thread below. This fella is working with Dr Mark Gordon I believe and is sharing the protocol prescribed to him. I personally am only taking NAC, Creatine, Vitamin C, High strength Omega 3 4grams DHA+EHA, Phosphatidylserine and Lithium Orotate per advice of the Youtube video linked below. Lithium protects the brain against Glutamate excitotoxicity, helps to regrow damaged neurons, and is also a HDAC inhibitor.

Something to talk about with your neurologist is low dose Fluoxetine, studies below. It has been highly successful for me in regulating my GABAergenic signalling, I used to not be able to go on the computer for more than 10 minutes or have a conversation / socalise with someone, without having severe symptoms of feeling wired & overstimulated. Now I have no issues. I would much rather take low dose Fluoxetine over benzodiazapines.


low non-serotonergic doses of fluoxetine and congeners increase allopregnanolone levels as their primary mechanism of action


SSRIs act as selective brain steroidogenic stimulants (SBSSs) at low doses that are inactive on 5-HT reuptake


Treatment with fluoxetine and other SSRIs can increase the concentration of allopregnanolone in rat and mouse brains, a response which can be seen within an hour and at doses lower than those required to inhibit the re-uptake of serotonin. Low doses of SSRIs can also increase allopregnanolone in human brains.


Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. We hypothesized that the increase of ALLO brain content induced by treatment with SSRIs could contribute to alleviating the anxiety.


Certain antidepressant drugs such as fluoxetine and fluvoxamine, which are generally thought to affect depression by acting as selective serotonin reuptake inhibitors (SSRIs), have also been found to normalize the levels of certain neurosteroids (which are frequently deficient in depressed patients) at doses that are inactive in affecting the reuptake.

Keep in touch man :slight_smile:


Hi mate,

Thanks a lot for the detailed answer, really appreciate it. I will take a read through all the info you linked and come to some conclusions for a potential treatment plan.

Out of interest - what dose of Fluoxetine do you microdose with? Will keep it in mind for the conversations with my Neurologist.


This is somewhat of a grey area as it has not been extensively studied in humans. I would be interested to hear the opinion of your neurologist, but from my research the equivalent dose for humans per the rat studies is something like 1-2mg (therapeutic dose as an SSRI is 20mg). I personally have been taking 2.5mg/d with great success, but I will now be dropping to 1.25mg/d, I want to find the minimum effective dose to ensure I am not effecting serotonin in any way.

For me, resorting to using an SSRI to treat my symptoms was a last resort as I know how poisonous these drugs can be, there are so many people on this forum suffering from PSSD. But I felt like I had tried everything, so many fucking supplements, lifestyle was perfect, yet my neurological symptoms of feeling extremely wired & overstimulated was still pretty debilitating. As I said, I would much rather take very low dose fluoxetine that has minimal effect on serotonin than take toxic benzodiazapines. Microdosing for me is a much safer way to go about it in my opinion.

Cheers mate, and good luck with your recovery journey, keep in touch

How can you get the dose that low? Do you take it as a liquid?

Comes as 20mg pills, I chop into 1/8ths with a pill cutter, which makes it 2.5mg, then because of the long half life you can just take it every second day to have it average out to be 1.25mg. The half life is something like 4-6 days, so you don’t need to be taking it daily.

I tried Desvenlafaxine (SNRI) at 50-100mg before Fluoxetine, and did not get the same benefits, so it’s definitely not placebo. Please be careful, so many people have been damaged from SSRIs!! I only want to share my experience.

Thanks mate - all the best with your recovery and will share any updates / progress I make

Hi @scott7777 ,

Glad to hear you at least saw some improvements since that damn first pill.

I took a single pill too and I’m still struggling with sexual sides, I was wondering if you had any and if it improved?

I am devastated and looking to hear experiences of other one pill users. It seems like we are the minority of the minority.


Hey man,

I know it sucks, I am 27 now but took the pill at the age of 21. Such a small minority of guys have to deal with hair loss at the age of 21 and then an even smaller minority are unlucky enough to have persistent PFS years later, let alone any side effects to begin with. We are the unlucky 1% of the 1%…! Anyway - we must keep up the fight!

I didn’t ever experience any sexual sides. Just very very severe mental / cognition issues which have gradually improved over time. I therefore can’t offer any specific advice on your condition.

That being said - I am a believer that this is reversible, either as your body gradually readjusts over time or by pharmacological interventions. This is so hard to treat because PFS is caused by interference with really complex endocrine and nuerosteroid pathways - way beyond issues with just Test / DHT levels (which is where most people look). Therefore, you need to know where to look in order to find what is off balance and infer any potential treatment options.

For myself and my mental sides, as per the above initial post, I am pretty sure that the drug interfered with my Allopregnenolone levels. When talking about sexual sides, I think there are a number of potential causes. Obviously there could be some sort of Test / DHT issue caused directly by Fin (although Test & DHT levels in sufferers are usually not in an abnormal range). Alternatively, through a few different pathways oestrogen levels could have been raised or potentially there could have been up/downregulation in androgen receptors.

Have you had any bloodwork done? I personally do not know enough to explicitly advise, however there are some online experts who understand this stuff down to a really granular level, one of whom is linked above (Leo Longevity), another is Derek from

It may be helpful for you to pay for a private consultation with one of them, they have a track record of helping correct chemical imbalances of PFS sufferers and can help you identify what bloodwork you should have done and thereafter what some potential treatment options could be.

These guys are not Physicians, therefore any advice they give etc should be discussed with a Doctor. However, I think most doctors are clueless in terms of knowing where to start - I think these guys could help you start looking in the right places.

Good luck man, keep fighting…

Yes man. The worst part of my story is I didn’t need it. It’s crazy.

I will look into those guys thank you very much, it is greatly appreciated. I had bloodwork done 4 days after the pill (which was fine) and I am going back this week to compare.

I really hope this is reversible. I considered suicide at least 50 times through this whole mess. And I was the happiest camper ever before.

How are you doing 6 years later?

Thanks again man,

Allopregnanolone is a positive allosteric modulator of the GABA receptors. Benzodiazepines are a positive allosteric modulator of the GABA receptors. Positive modulators of the GABA receptors are “enhancing” the GABA receptors reaction to GABA. Benzodiazepines of course are doing this to a “stronger” degree compared to naturally made Allopregnanolone.

There are positive and negative allosteric modulators of the GABA receptors

3a-diol is also a positive allosteric modulator of the GABA receptor

Pregnenolone sulfate is a neurosteriod that I believe has been overlooked. Pregnenolone sulfate is a negative modulator of the GABA receptor. I am assuming that the GABA receptors need a proper balance of positive and negative modulation.

I’m flagged low in saliva pregnenolone sulfate suggesting that my GABA receptors lack NEGATIVE allosteric modulation. I have flagged high amounts of 3a-diol in my urine suggesting that my body is excreting/getting rid of high amounts of the neurosteriod 3a-diol which as previously stated is a POSITIVE allosteric modulator of the GABA receptors. I have highish Allopregnanolone in my urine suggesting that again my body is excreting another major natural POSITIVE allosteric modulator of the GABA receptors.

So I’m pretty sure everyone can see where I’m
trying to go with this. It’s possible evidence of a GABA imbalance/mis-regulation of some kind. Maybe what’s going on with me is that without negative allosteric modulation it makes sense that my GABA receptors could become too sensitive and then my body gets rid of positive allosteric modulators to “try to compensate”.

We also know that I agonized my NMDA receptors with just a slight increase in glutamate recently and I experienced “a crash” that felt identical to my Saw P crash seven years ago. I say “just a slight increase in glutamate” because I had before and after urine neurotransmitters testing done and I only had slightly higher glutamate in my urine after taking L-Glutamine for 64 days in between both urine neurotransmitter tests.

So because GABA receptors are the main inhibitory neurotransmitter receptors and the glutamate receptors are the main excitatory neurotransmitter receptors it’s important that these two things need to be in proper balance with each other. So if the GABA receptors are “out of wack” due to improper balance of positive and negative allosteric modulation it makes sense that the glutamate receptors would now be “out of wack” now as well. This could explain my “PFS type crash” response to simply agonizing the Glutamate receptors “just a little”.

We also have the user thisisarealbummer who came to a similar conclusion based on his own experience. And we have the other user who is narrowing in on the glutamate receptors who’s name I can’t remember at this moment.

I want to know if others would show a similar pattern if they were to have their saliva Pregnenolone sulfate, urine Allopregnanolone and urine 3a-diol tested. Two different tests from a company called ZRT lab are required to have all three things tested. For weeks I have been in contact with a ZRT lab provider in an attempt to make these tests available for others. I really want to know if what I’m seeing with low saliva pregnenolone sulfate, high urine Allopregnanolone and high urine 3a-diol can be replicated in others. The testing is not cheep but if this functional health company comes through for us it will be as cheep as possible and not require a doctors order. I may know more this week.

If my current line of thinking is correct in my case in theory all it may take is increasing pregnenolone sulfate because I’m low in it and its a negative allosteric modulator of the GABA receptors. So maybe without a proper balance of negative and positive allosteric modulation the GABA receptors may not be able to function properly and this may throw off a proper balance between GABA and GLUTAMATE the bodies main inhibitory and excitatory neurotransmitters. This is just a theory though. We have not replicated my low saliva pregnenolone sulfate or my high urine Allopregnanolone and 3a-diol in anyone else yet. I’m trying to get others to get tested .

Allopregnanolone and 3a-diol are positive allosteric modulators of the GABA receptors

Recently I had a urine neurotransmitter test done. It showed I was low in Glutamate. I took a bunch of amino acids and SAMe and increased the amount of glutamate that my body was producing confirmed by a follow up urine neurotransmitter test. I crashed. Like a complete PFS type crash. I was so wired that I stayed up for 9 days. This was what happened to me when I took saw P seven years ago. The only thing that allowed me to sleep was benzodiazepines which I agree we should not be taking. Scared to death of continuing to get worse I stopped taking everything. Eventually I built up enough courage to add glycine back in which substantially helped me. I currently need at least 3500 MG’s of glycine to sleep. Interestingly even with taking 5000 MG’s of glycine I still have lowish amounts of glycine in my urine suggesting that my body needs that glycine. Probably because it’s inhibitory and maybe because I have a GABA/GLUTAMATE receptor imbalance. So maybe my body is using all this supplemental glycine to bind to the glycine receptors to compensate for the GABA receptors, the bodies main inhibitory neurotransmitter that may not be working properly. Glycine also binds to the glutamate receptors as well


Why did you take it if you didn’t need it out of interest? Looking to preserve the hair you have?

Good luck man - I am sure that one way or another you will begin to improve. But keep me updated in terms of consultations & bloodwork etc.

I am around 95% healed now and I have learned to deal with the other 5%. I definitely continue to improve year on year though. I am pretty sure in the future I will be able to forget about this mess. It’s been a slow journey to where I am now though and mostly suffering in silence due to the embarrassment of it all.

Take care mate

Thanks a lot for your response - this is insightful and interesting.

I would also agree that it is unlikely a case of just lacking positive modulation of GABA receptors and that a general mis-regulation is likely a more accurate description for PFS sufferers.

Can I ask what your symptoms were at the time that you hypothesise you had a lack of negative GABA modulation? I assume that such symptoms would be the opposite of ‘feeling wired’ and the symptoms we know that you get form a lack of positive modulation?

I would certainly be interested in neurosteroid tests. I suffered in silence for a long time because I couldn’t find a doctor that understood my condition. I think it is important that we create a set of possible diagnostic tests - that being said I live in the UK which may be prohibitive on the assumption you are further afield.

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Still one of the most promosing theories.
Dysrupted 5ar=>Neurosteroid downstream=>desensitized (?) GABA what can explain no respond to alcohol etc. like you are always “high”. What success you had exactly with low dose SSRI? I also think about to try it.

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My response to alcohol after getting PFS is very limited compared to pre PFS. And believe me I know because prior to PFS I liked to drink haha

Now it’s like I go right to the hang over and feeling like crap and skip the good feeling . So I stopped drinking a long time ago

I agree that this is one more clue that further implicates the GABA receptors. My theory is that if the GABA receptors which are the bodies main inhibitory neurotransmitter did in fact become intolerant per thisisarealbummers theory then the glutamate receptors as well as possibly the dopamine, adrenaline and noradrenaline receptors may all become mis-regulated in an attempt to match the intolerant GABA receptors


So I’m currently 36. I got PFS from Saw-P at age 26. At that time I got all the sexual sides only. Not that sexual sides only don’t suck because they do. At age 29 I took saw-P again and developed digestive and insomnia issues on top of sexual sides.

Then recently as in this past summer after taking my recovery attempts to the next level I had one of the most advanced saliva hormone tests done currently available in a normal clinical setting. This is how I discovered that I’m low in a not so well know neurosteriod called pregnenolone sulfate. I’ll edit this post and include a chart later so that you can see where and how in the hormonal pathway pregnenolone sulfate is being made. Most of the hormonal pathway charts you find on line will not include it.

Then i started googling the heck out of pregnenolone sulfate leading me to discover that it’s a neurosteriod that negatively modulates the GABA receptors. The exact opposite as Allopregnanolone, 3a-diol and benzodiazepines which act as positive allosteric modulators of the GABA receptors.

Now if I’m low in the bodies main negative allosteric modulators of the GABA receptors it’s my theory that this is a possibly mechanism/scenario in which the result is that the GABA receptors may stay in a constant state of insensitivity/down regulation in order to avoid “excessive positively modulation”. Because maybe it’s the case that the GABA receptors need a proper balance of negative and positive modulation in order to stay “balanced” because after all that’s the point of a “modulator”.

So if there is no negative allosteric modulator present because there is no or not enough pregnenolone sulfate then maybe the “next best thing”is that the GABA receptors become less sensitive to the effect of the neurotransmitter GABA. And if this happens maybe the bodies main excitatory neurotransmitter glutamate adjusts to match the misregulated main inhibitory neurotransmitter GABA

Keep in mind that low pregnenolone sulfate has not been replicated in anyone else yet. Also keep in mind that the exact imbalance that could results due to having low pregnenolone sulfate could be different then my proposed mechanism. I’m simply going with the most logical outcome of outcomes that could in theory result from the lack of negative allosteric modulation of the GABA receptors.

I think the lab may send a test to the UK. I will find out and let you know.


Ok I follow your theory - makes sense and thanks for explaining. Certainly in line with my original line of thought.

Please do let me know about test availability in the UK, I am very interesting at exploring a deeper level of testing vs what you can infer from simple bloodwork. It would be great to collect results from a wide number of PFS sufferers.

On a side note, I am glad you have mentioned that you crashed from SP. My hair loss continues to steadily progress and this is a good reminder to stay away from anything that inhibits 5AR at all costs!

Thanks again and keep in touch

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An interesting finding indeed. Please keep us posted as you continue to delve into this.

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We can just try low dose Fluoxetine for it.