A closer look at Neurotransmitters for possible therapeutic benefits

[5-alpha-victim]

@dragonslayer123

Looking at the reference range of the allopregnanolone on ZRT labs LCMS salvia hormone test we can see that the reference range is as follows:

LESS then 15 pg/mL

So when I first seen this I was confused. So I emailed the owner of ZRT lab and he explained it to me. When a lab uses a reference of “Less then 15 pg/mL” they are saying that anything less then 15 pg/ml is normal and anything over 15 pg/mL is high. This type of a reference range is only telling you if your value is high.

In this case because my allopregnenolone was not high it’s considered normal as far as this reference range is concerned. However it’s not actually telling me what my allopregnenlone level is. It’s just telling me that it’s not high. The doctor/researcher/scientist who owns ZRT lab explained that in certain instances when patients go on Finasteride their allopregnenolone can go high which can make someone feel shitty so this test to an extent can be used to monitor patients while on Finasteride. But like I said this tests is not telling me if I am producing low amounts of allopregnenolone or not. It’s just telling me that I do not produce high amounts of allopregnenolone.

Ok so now based on this test I know that I don’t produce high amounts of allopregnenolone. But I am still left thinking “do I produce low amounts of allopregnenolone”?

So the reason why I actually got ZRT’s urine hormone metabolite test was to see if I was low in allopregnenolone or not. Again I knew that I was not producing high amounts of allopregnenolone from ZRT’s LCMS salvia test but I still did not know if I was producing low amounts of allopregnenolone. So I got the urine test knowing that ZRT’s urine hormone metabolite test (the one that you ordered) would not only tell me if I was producing low amounts of allopregnenolone but that it would also tell me exactly what my urine allopregnenolone levels are. Why? Because ZRT’s labs urine hormone metabolite test has a full reference range for the urine allopregnenolone value. It’s not just saying “less then such and such is normal” because it’s not high. It’s actually providing a normal reference range like we are use to seeing in our blood hormone labs.

So now I get my urine hormone metabolite allopregnenolone results back and see that I am peeing out top of the reference range level allopregnenolone levels….

Obviously common sense makes me ask my self this question:

If I know I am not producing high amounts of allopregnenolone per the saliva test THEN WHY AM I PEEING OUT HIGH AMOUNTS OF ALLOPREGNENOLONE???

I’m either producing normal or low amounts of allopregnenolone and I am peeing out most of it? Well why? If I was producing high amounts of allopregnenolone I would suspect to see high amounts of in my urine. Produce more in my mind means pee out more. But I am peeing out more in spite of not producing high amounts of it. This is what catches me eye. Get my logic?

To answer the rest of the questions:

Progesterone converts to 5a-DHP via the 5AR enzyme. Then 5a-DHP converts to allopregnenolone via the 3a-HSD enzyme.

Obviously I understand that a lot is unknown about allopregnenolone and the implications with messing with it. Which is why there should not be a drug that messes with it without the impact of messing with it having been properly studied. They do know that allopregnenolone is a positive allosteric modulator of the GABA receptors. My understanding of what this means is that not only is allopregnenolone agonizing the GABA receptors but it “modulates” them. In my mind this means that allopregnenolone is making sure there is enough action on the GABA receptors adjusting their sensitivity in a way that allows them to respond “positively” to GABA. Opposed to pregnenolone sulfate which is negatively modulating the GABA receptors hindering the GABA receptors response to GABA. It’s also my understanding that the GABA receptors need a proper balance of positive and negative modulation to work properly. The GABA receptors should not be too sensitive but they should not be too insensitive. Which is why I am assuming “mother nature” gave us neurosteriods that both positively and negatively modulate the GABA neurotransmitter receptors. So this is why I am theorizing that I have a GABA receptor imbalance. Because I do not appear to be producing enough pregnenolone sulfate while I am peeing out top of the reference range amounts of allopregnenolone. This to me suggests too little negative modulation of the GABA receptors which may be why my body is peeing out as much allopregnenolone as possible in order to avoid too much positive modulation in lack of negative modulation. If you read about what can happen when the GABA receptors are not balanced things go bad. Like seizures and all kinds of horrible things. So maybe my body is smart enough to stop as much positive modulation of the GABA receptors as possible by getting rid of it’s allopregnenolone in the urine knowing what the outcome will be if the allopregnenolone hits the GABA receptors with not enough negative modulation (pregnenolone sulfate)

Disclaimer:

This is all theory based on my own labs. So I am not claiming to know what PFS is. I am simply trying to explore my theory further in others

[Alex50]

What are your neurological symptoms?

I agree an imbalance in allosteric modulation of the GABA-a receptors is likely in PFS. There is a sweet spot. What are your symptoms? My theory is;

• Too little allosteric modulation, low allopregnanlone, results in anxiety, feeling wired, overstimulation and insomnia (this is what I’m dealing with),
• Too much allosteric modulation, maybe high allopregnanlone, results in anhedonia and apathy. These are the individuals that do not respond to alcohol and benzodiazapines.

I fall into the first class of individuals, I find great benefit in using benzodiazapines, ashwagandha and progesterone, which are all postiive allosteric modulators.

It would be interesting to see if you fall into the latter class of individuals given your high allopregnanlone per your urine test. The people in the latter class may benefit more from negative allosteric modulators, like pregnanlone sulfate.

[5-alpha-victim]

@dragonslayer123

Here is ZRT labs sample saliva LCMS test:

lcms-saliva-sample-report.pdf

Here is ZRT labs saliva LCMS test on their Website:

Saliva Testing | ZRT Laboratory

Scroll down a little and you will see it. It’s under saliva testing options and listed as:

“LCMS Saliva Steroid Profile – E2, E3, E1, EE, PregS, Pg, AlloP, 17OHPg, Adione, T, DHT, D, DS, 7keto, 11DC, C, Cn, Ccn, Ald, Mel, ANZ, FIN & LTZ”

Here is the company that told me that you guys could order it from. They said that you can text, call or email them and ask to get the test through them

https://letourneaus.net 1

978-475-7779

aliciap@letourneaus.net

This is “ ZRT’s gem” and they make it the hardest for patients to get out of any of their other tests. You have to get this through doctors or specialty pharmacy’s. The company above is a speciality pharmacy who told me over the phone they will sell the LCMS saliva test to PFS patients without a doctors order. They told me over the phone that they will simply send you the test kit and that you would pay ZRT directly after sending ZRT lab your saliva sample. For the record I have spent hours upon hours on the phone with doctor offices and specialty pharmacy’s and this is the only one I could find that told me over the phone that they are willing to simply send you the LCMS saliva test kit with out a doctors appointment. For now though let’s just focus on your urine hormone metabolite test though so that we don’t get confused.

I’ll post the instructions shortly regarding how to supply the urine sample correctly . We want to follow the instructions to the T so that we can trust the results.

[5-alpha-victim]

@Alex50

Well if we are right about what we have in mind then perhaps all of my symptoms are neurological. Thinking along these lines the first thing I tried was increasing serotonin. I seen that the amount of serotonin in my urine was not in the optimal range. So I took serotonin precursors 5-HTP, L-Tryptophan and serotonin co factor vitamin B6 in order to see if it would increase the amount of serotonin that I was peeing out.

We know that we don’t know exactly what are bodies are producing based on what the body is getting rid of in the urine. Because what’s in the urine is what the body is eliminating of a certain thing. Not the exact amount being produced.

But it is telling us if the body is getting rid of high amounts of certain thing. It’s also giving us a clue as to what we are producing.

For example we know that it’s not the cause that I’m producing extremely low amounts or no Allopregnanolone. Because how could I be producing extremely low amounts of or no Allopregnanolone if I have top of reference range levels of it in my urine. I cant eliminate something from my body in high amounts in my urine if I’m producing no or low amounts of it.

I think this is an important point because in Melchangi’s study the PFS group had extremely low amounts of Allopregnanolone in their CNS and in their plasma. Melchangi’s Allopregnanolone findings in his study make it appear that the PFS group in his study are producing low amounts of Allopregnanolone. This suggests that the 5AR enzyme and or the 3a-HSD enzyme are not working. BUT what if the PFS patients in his study had high amounts of Allopregnanolone in their urine? Would this change his way of thinking? Because now we would know the PFS patients in Melchangi’s study had low CNS Allopregnanolone even though their bodies are still producing it. In that case it would seem like we are getting rid of the Allopregnanolone (even though we shouldn’t be getting rid of it) in order to keep it low in the CNS.

So when I increased the amount of serotonin I was peeing out my gut turns back on and my constipation goes away. Three times now I have stopped the serotonin supplements listed above and my constipation comes back. And when I start taking those specific supplements again my constipation goes away. So I think in my case the constipation is neurological in the regard that my body can’t properly regulate serotonin for some reason. If you google serotonin you will see that most of the bodies serotonin is produced in the gut and that it stimulates intestinal movements.

I also got severe insomnia after the second time I took saw p. And severe insomnia again recently after taking several amino acids including the amino acids that I listed above for serotonin production. The recent insomnia was very similar to the insomnia that I got from the Saw P when I was 29 seven years ago. Except this time I did not take saw P or a 5AR inhibitor. I simply took amino acids that convert to neurotransmitters in the body. So in a way I gave my self PFS from taking amino acids recently. This is why I think that it’s neurotransmitters. The insomnia that I got recently from taking the amino acids had me up for 8 days straight followed by weeks of hardly any sleep . So this felt neurological

I get every PFS sexual side. These sides got worse from the amino acid combination I was taking as well. Amino acids increase neurotransmitters. So the sexual sides to me feel neurological.

But it’s confusing. Because the serotonin amino acids that I listed above cure my constipation while the combo of all the amino acids I was taking essential cause PFS in me . So for me it seems like a neurotransmitter imbalance.

Another thing to consider about pregnenolone sulfate is that not only is it negative allosteric modulator of the GABA receptors but it’s also a positive allosteric modulator of NMDA receptors. The GABA receptors are the bodies main inhibitory neurotransmitter receptors and the NMDA receptors are the bodies main excitatory neurotransmitter receptors. Imbalance in either GABA or NMDA receptors could cause these issues and the bodies main inhibitory and excitatory neurotransmitters should be balanced with each other. If you read about GABA and NMDA receptors you will see what I mean

So low pregnenolone sulfate (like I’m flagged low in) could implicate issues with both the GABA and the NMDA receptors. Because it’s a positive allosteric modulator of the NMDA receptors and a negative allosteric modulator of the GABA receptors. So maybe I have a NMDA/GABA receptor imbalance. I’m hoping someone else will be low in saliva pregnenolone sulfate in order to increase the likely hood that I’m onto something.

What are your symptoms ? Which of your symptoms does benzodiazepines, ashwagendha and progesterone help ?

Benzodiazepines are the only thing out of the arsenal of things that I tried to treat my recent PFS like insomnia with that worked. When the recent insomnia relapse was at its worst benzodiazepines are literally the only thing that would help it. I wonder though if the benzodiazepines will ultimately make imbalanced GABA receptors even worse though. If this theory is right we also need to think outside the box. Maybe if the GABA receptors lack negative allosteric modulation the GABA receptors stay down regulated/insensitive in order to avoid the reaction of having only positive allosteric modulation. Maybe the body in the case of lack of negative modulation pees out as much Allopregnanolone and 3a-diol as possible and makes the GABA receptors insensitive somehow. If this is true then in theory taking benzodiazepines which are prescription strength positive allosteric modulators of the GABA receptors only makes things worse in the long run. I don’t know though just throwing out ideas…

For me benzodiazepines only helped me sleep in my insomnia state. Of course now that Im getting good enough sleep I’m not taking the benzodiazepines. Benzodiazepines did not help me with the constipation or the sexual sides. So if taking prescription strength allosteric positive modulator of the GABA receptors does not help my constipation or my sexual sides I’m assuming that this means another factor/factors are at play that causes these issues. I have learned a lot though about my imbalances. Positive allosteric modulation of the GABA receptors temporarily helps the insomnia. Increasing serotonin production in the GUT helps my constipation. So I’m obviously looking for the key to the sexual sides and I suspect the answer also lies in neurotransmitters and neurotransmitter receptors

In a perfect world if gods on my side I increase pregnenolone sulfate and everything becomes balanced and falls back into place

[Alex50]

My symptoms include feeling wired, overstimulated, feel fried in the brain, inability to tolerate stimulation (like scrolling the internet or playing a stimulating video game makes me extremely wired), issues sleeping, etc. My GABA is heavily dysregulated. Benzodiazepines make me feel 100% normal, but I’m obviously not going to depend on this. I’m picking up some high quality CBD oil next week to try instead. Low dose fluoxetine did help initially, but I’ve decided to come off as I don’t want to be using an SSRI given my sexual dysfunction. It would be interesting to see if what a urine neurotransmitter test said, although I don’t believe they represent what’s in the brain or CNS at all. My current efforts are focused on hormone therapy and fixing my gut microbiome.

[bigboss]

I feel you very much. That overstimulation from everything is exhausting. I become stupid and anxious. Like you’re drunk without positive effects.

Do you feel something like the inability to plan or thinking abstract, like something is physically blocking you from complex thoughts? And have you noticed any pattern in these symptoms fluctuations? According to my diary, they are fluctuating in a cycle of around 28 days. So I think it very much related to steroids.

[5-alpha-victim]

@Sugarhouse

I completed he survey

[Sugarhouse]

Thank you @5-alpha-victim - amazing work!

[5-alpha-victim]

@dragonslayer123

I hope all is well and you received your urine neurotransmitter and hormone metabolite test kit with no issues.

The first thing I recommend is not rushing into providing the sample. Just open the kit, leave the paper cards that get exposed to the urine in the zip lock plastic bag that they come in and get organized. Let it sit for a couple of days, learn the instructions and what to avoid eating prior to taking the samples. If the instructions are not followed correctly the data we get is useless because we wont be able to trust the results.

Watching this instructional video on how to provide the urine sample is a must prior to providing the sample. You can click on this link and scroll down to urine collection video. It’s called 'urine collection video" and is the 3rd one down. Ignore the salvia and blood collection videos above it because for now they are not relevant. it’s easy to follow video.

How to Collect Your Sample | ZRT Laboratory

A couple of things about the video:

The video is saying that the better of the two methods is to hold the sample cards and urinate on them. DO NOT USE THIS METHOD. The video is wrong. This is not the better of the two options.

Instead use the urinate in the cup method. Use a glass cup. Clean the cup with soap and warm water. Make sure you go over the top with making sure that you wash all the soap out of the inside of the cup after cleaning it. Use clean paper towels to dry the inside of the cup down. Then urinate in the cup all the way to the near top. Dip the paper card into the cup exactly how the video shows you to do it but dip it all the way to the last black line. Directly up to the last black line and take it out of the cup. The video will show you how the card flips open and how to let it dry. Follow the instructions in the video exactly how it’s saying to let the card dry. There is four cards which means 4 samples through out the course of the day. Each time clean out the glass cup with warm water and soap and dry with clean paper towel before urinating it again for the next sample. If you have any questions about how to handle the paper cards after they are saturated in the urine and how to let the cards dry before folding them closed please let me know. I can answer all questions in vivid detail so we don’t F this up.

I will also post the written instructions that explain what not to eat prior to providing the sample. You will also have a copy of these instructions that come with the kit. I figure this is enough to digest for now and like I said don’t rush to get it done. We are better off waiting a couple of more days before we have the results and getting it right. The rush is getting the kit in the mail to get it back to ZRT after it’s completed and packaged up. Not providing the sample. No rush for this. The pre paid shipping label is a 2-3 day delivery back to ZRT so they get it timely before the sample goes bad. And ZRT tests it as soon as they get it

[dragonslayer123]

Yes I was thinking just that. I received it on friday and was reading the instructions. Wanted to take my time with it. You sent good information for me just now and I will let you know when I send them out.

[betweenjobs]

@bigboss

That overstimulation from everything is exhausting. I become stupid and anxious. Like you’re drunk without positive effect

This is me %100. I can use maybe a tenth of my brain power. Can’t keep up intelligent conversations, can never think of words, socially withdrawn, don’t feel connections with my peers, tired and drained mentally all the time. If I sit and do nothing I feel fine. Yay

If anyone has been treating this group of cognitive sides , step up and share.

[5-alpha-victim]

The more I experiment with amino acids the more I see how strongly they affect PFS for me for the good and bad

[betweenjobs]

Aminos have made me worse in the past so I stay away from them
Dieting either gives me diarrhea or constipation so I stay on a fairly normal diet to keep things moving. I tiny bit of metamucil and a half a multi vitamin every other day seems to do the trick.
Also I avoid cows milk, rich portions of gluten, rich portions of tomatoe and soy.
Every hormone I have tried has had a negative effect- immediately converts to estrogen, haven’t tried an AI because of the anecdotal stories of people getting worse. However i know nothing about them. Antidepressants , wellbutrin made feel like shit , low dose fluoxetine immediately gave me ed and took away my attraction to women within a week and made me feel like a zombie. So what the studies about it not having the effects of ssri at the low dose is bull shit at least for me, made me poop incredibly well but that was it, so I mmenditarly stopped.

[5-alpha-victim]

Yea…

Aminos made me worse in some areas as well but also better in some areas. For me this clearly shows the answer lies within neurotransmitters . Not saying that I have a solution yet. But I have the problem

Which amino acids made you worse and in what areas did they make you worse ?

Also,

“Fluoxetine, sold under the brand names Prozac and Sarafem among others, is an antidepressant of the (SSRI) class”

“SSRIs increase the extracellular level of the neurotransmitter serotonin by limiting its reabsorption into the presynaptic cell”

When I increase serotonin production with
L-Tryptophan and 5-HTP I pooped a lot better. So this is what I’m talking about. We need to figure out why this is and why other areas get worse when we increase serotonin and fix the constipation

You limited serotonin’s reabsorption which in layman’s term I think this means “the serotonin hangs around the serotonin receptors longer”.

This is messing with the way things should and should not be working so I don’t think we should do this. Increasing your bodies own natural production in my opinion is the safer option . I did this with proof…

I took a urine neurotransmitter test . Then I took the amino acids and co factor that produce serotonin in the body. Then I took another urine neurotransmitter test and I was peeing out higher amounts of serotonin. So before everyone goes nuts with the “yea but that’s not telling you exactly how much serotonin is in your CNS”. Not saying it is. But it did tell me my body produced more serotonin in response to the L-Tryptophan and 5-HTP and that during this time I was pooping like the good old days

I suspected it was because most of the bodies serotonin is actually produced in the gut before “it’s taken” to the brain and that it stimulates intestinal contractions. But because you “artificially” with a horrible pharmaceutical “made your serotonin hang around longer in the brain” and achieved the same result now I’m thinking that it’s something at the receptor level with giving the serotonin receptors more serotonin that’s helping us poop better

My main point is that if EVERYONE was experimenting with this path maybe we could know way more …

And just so you know taking other amino acids put me in relapse insomnia and I felt exactly like I did when I got PFS again with the Insomnia

So I know I sound like a broken record but for me to see an almost complete reversal of the constipation after 7 years on amino acids and almost complete relapse insomnia on amino acids after 7 years this is compelling…

Not in the regard that it’s providing a clear solution but in the regard that’s it’s telling me where the problems lie at least in my own case. And possibly in others seeing that you experienced similar benefits in the digestive issues when increasing serotonin

[smphead]

Derek and that other Guy has a lot knowledge about pfs.

Progesterone Use For Post-Finasteride Syndrome And Men On TRT

[dragonslayer123]

@5-alpha-victim its relevant. give it a listen its not too long. They talk about instead of trt look to the neurosteroid level for PFS as allopregnanolone is severely overlooked when it comes to 5aR. Ultimately they think it must be reversable. Thats a summary

[5-alpha-victim]

I misunderstood. I can see why it’s relevant

Interesting that both of these guys are either on or have taken Fin

They are deff knowledgeable generally speaking. I question the guy in the white hat’s decision to stay on fin for prostate health. Fin is thought to lower your over all chance of getting prostate cancer but it’s also thought to increase your over all chances of getting high grade aggressive prostate cancer. They are also making statements about PFS and if I’m following neither of them got PFS?

The guy in the white hat is also assuming we have low Allopregnanolone which I can see why seeing that Melchangi’s study found low Allopregnanolone in the CNS of the PFS group. But myself and thisisarealbummer both have high Allopregnanolone in our urine and we don’t supplement Allopregnanolone. Ronnie99 does not have high Allopregnanolone in his urine but it’s not low either. Melchangi’s study also found low
3a-diol in the CNS of the PFS group. And me and Ronnie99 both have high 3a-diol in our urine. So I don’t know I’m not sure if we are really just “low in Allopregnanolone” from the standpoint that prog is not going to 5a-DHP via 5AR and 5a-DHP is not going to Allopregnanolone via 3a-HSD. Because this is how it’s made and I’m clearly making it. Like I was telling this other guy giving me crap in another thread we can’t not be producing something that’s high In out urine. I mean it did not magically appear in our waste LOL. Guy in white hat says all we need to do is increase Allopregnanolone. Don’t think he’s right about that but either way interesting video to see these guys talking about this

[dragonslayer123]

Yeah its a real bummer when they say they just dont understand how PFS can happen. Really just denying others experiences is pretty lame. But Dereck the main guy has really changed his tone and at least acknowledges that people can suffer from PFS. And it is really frustrating when says he hasnt talked with any of his clients who have had PFS who haven’t recovered because he charges $1000 just to talk to him for 30 minutes. I would talk to him tomorrow to share my experience if it wasnt $1000. It is also very frustrating that I listened to this guy among others that all said finasteride is safe no problem. He has changed his tone and definitely would have altered my choice of taking finasteride in the first place. No blame on him definitely my choice.
I still think a spinal tap would be very beneficial for the PFS community but what do I know.
Also my hormone sample has been delayed because I decided to drink this weekend. I dont want to mess it up.

Also also what do you think of taking progesterone as a supplemental treatment?

[Gord]

Wow! $1000 for a 30 minute chat! is that for real?

I’d be expecting to hear the meaning of life for that price

[5-alpha-victim]

Who is he anyway ? Why do people pay him for his information? Is he a physician?

If several of us end up having high or highish Allopregnanolone and 3a-diol in our urine and if we also have low Allopregnanolone in our CNS this would be compelling. If several of us have high or highish Allopregnanolone in our urine I want to send this info to Melchangi.

It will be very hard to accomplish but if let’s say 10 of us have high or highish Allopregnanolone in our urine and then if we could get 10 non PFS guys to have the test done and they don’t have high Allopregnanolone in their urine maybe Melchangi would be all over that to do a new research study with. That’s my ultimate objective with this. Wishful thinking but I never thought I would even get this far to get someone else to get this done .

Also if you have high or highish Allopregnanolone and 3a-diol in your urine maybe the foundation would pay to have some more volunteers to get this done so that we can see if it’s a pattern amongst a lot of us

That’s good that you delayed it. I’m going to post the diet instructions just to make sure that we are on the same page with the things to avoid prior to taking the samples

I read lightattheends Progesterone supplementation thread years ago. I did try it very briefly and literally felt nothing from it for the better or the worse. Seeing that others have claimed success from cycling progesterone it is something that I have always thought about revisiting. Maybe some day I’ll trial progesterone at a high dosage and with a different hopefully better progesterone supplement.

Have you ever tried it ?