Area1255's new theory to PSSD cure

[Astral kid]

Area-1255: *NEW THEORIES* on How to CURE AntiDepressant Sexual Issues 2019 (CURE PSSD NEW THEORIES 2019)

@Helen I was curious to know what you thought about this theory.

 

[Astral kid]

@talkingant @barbaar @raven thought you guys would be interested if you haven't already seen this.

 

[diffi]

I have read your lines. Dude, I am fucking impressed by your work.
I have never been impressed more before that.
I guess Melcangi &Co.are not going the right direction re pfs. The most important thing is to understand how one pill - and therefore dht is reduced for about one week - can cause such devastating symptoms. For sure, the brain is involved as one doc in France showed that in an interview by presenting MRIs. And fin alterates even microbiom.
I like your post about masculinity.
Great work.

 

[Helen]

Area-1255: *NEW THEORIES* on How to CURE AntiDepressant Sexual Issues 2019 (CURE PSSD NEW THEORIES 2019)

@Helen I was curious to know what you thought about this theory.

I wrote similar thing , Serotonin increases CRF. CRF blocks androgens.

over time CRF gets downregulated.

so end effect low ACTH output.


SO you need to block serotonin receptor. restore CRF

I wrote very similar thing right here.
https://www.hackstasis.com/threads/upregulated-gr-cortisol-receptor-theory.1648/ post 12

You need to also understand that some people have high LH in PSSD. so Grhn is not downregulated.




In actuality anything that will block serotonin receptor, will lower brain copper.


In PSSD there is high histidine, and zero conversion of it to histamine, that is because metabolism is slow.

and histamine will causes potassium to leave the cell. which body does not want, since body raises progesterone.

when you have no histamine and no acetycholine, you have NOTHING for sexual arousal.

 

[talkingant]

I think what is important here is NMDA/glutamate. Some PSSD types may be related to dysfunction of the hypothalmus. This would explain HPA axis issues we see in some people, like myself with low cortisol. A hypoactive hypothalmus reduces glutamate firing in general.

What we should try to do is improve glutamate firing either by improving the HPA axis or via other receptors. Glutamate is heavily involved in hedonistic and emotional processing. Glutamate firing is likely inhibited by high serotonin. It is also inhibited by its autoreceptor, mGluR2. Downregulating mGluR2 will increase glutamate levels.

Psychedelics like psilocybin activate the 5HT2A-mGluR2 complex. This is a receptor complex formed by a combination of 5HT2A and mGluR2 receptors. Only some 5HT2A agonists like psychedelics activate the 5HT2A-mGluR2 complex. By activating it acutely, mGluR2 can be downregulated afterwards. This could explain why some people improve after psychedelics like mushrooms, because it heavily activates 5HT2A-mGluR2, downregulating mGluR2. Then after the drug leaves the system you are left with a downregulated mGluR2, allowing glutamate levels to rise. This effect lasts anywhere from days to months, but it is not clear if it can be permanent.

Direct acute mGluR2 agonists could have a similar effect, but there are not really any readily available safe options. Allosteric modulators of mGluR2 could also work, but these are also not readily available.

Now onto the HPA axis:

As has been previously suggested, downregulating GR (cortisol receptor) on the pituitary gland could help people with low cortisol from overly sensitive GR. Simply increasing cortisol is probably not enough to fix things, as the HPA axis is complicated (mathematical model). Activation of GR actually upregulates GR on the pituitary gland, so more cortisol = more sensitive GR = even more cortisol! This is one of the ways PTSD/CSF could happen. High stress leads to high cortisol which upregulates GR. Then the patient will be stuck with overly sensitive GR. This leads to being stuck in a state of low cortisol, sensitive GR, and underactive hypothalmus, leading to less glutamate firing = less pleasure/emotions.

This study uses the HPA mathematical modelto suggest that external stressors applied for the right duration at the right time can REVERSE the low cortisol, oversensitive GR state! So stress yourself out just a little bit, and you might be able to paradoxically reverse HPA axis dysfunction! But figuring out what counts as enough "stress" and for how long is very difficult.

Another study analyzes the model and suggests GR antagonists can return one from this state to normal. Unfortunately RU-486 probably won't work for this because it doesn't enter the brain, and instead actually raises cortisol in the brain by blocking cortisol from crossing the blood-brain barrier. One would need to antagonize GR on the pituitary gland in the brain or somehow lower cortisol levels.

I should probably make a new thread on this to organize it better. But basically, we want to increase glutamate in the brain by fixing the HPA axis, if that is indeed a problem for you. Additionally, high serotonin or upregulated 5HT2A receptors could be a problem inhibiting glutamate.

 

[Astral kid]

I think what is important here is NMDA/glutamate. Some PSSD types may be related to dysfunction of the hypothalmus. This would explain HPA axis issues we see in some people, like myself with low cortisol. A hypoactive hypothalmus reduces glutamate firing in general.

What we should try to do is improve glutamate firing either by improving the HPA axis or via other receptors. Glutamate is heavily involved in hedonistic and emotional processing. Glutamate firing is likely inhibited by high serotonin. It is also inhibited by its autoreceptor, mGluR2. Downregulating mGluR2 will increase glutamate levels.

Psychedelics like psilocybin activate the 5HT2A-mGluR2 complex. This is a receptor complex formed by a combination of 5HT2A and mGluR2 receptors. Only some 5HT2A agonists like psychedelics activate the 5HT2A-mGluR2 complex. By activating it acutely, mGluR2 can be downregulated afterwards. This could explain why some people improve after psychedelics like mushrooms, because it heavily activates 5HT2A-mGluR2, downregulating mGluR2. Then after the drug leaves the system you are left with a downregulated mGluR2, allowing glutamate levels to rise. This effect lasts anywhere from days to months, but it is not clear if it can be permanent.

Direct acute mGluR2 agonists could have a similar effect, but there are not really any readily available safe options. Allosteric modulators of mGluR2 could also work, but these are also not readily available.

Now onto the HPA axis:

As has been previously suggested, downregulating GR (cortisol receptor) on the pituitary gland could help people with low cortisol from overly sensitive GR. Simply increasing cortisol is probably not enough to fix things, as the HPA axis is complicated (mathematical model). Activation of GR actually upregulates GR on the pituitary gland, so more cortisol = more sensitive GR = even more cortisol! This is one of the ways PTSD/CSF could happen. High stress leads to high cortisol which upregulates GR. Then the patient will be stuck with overly sensitive GR. This leads to being stuck in a state of low cortisol, sensitive GR, and underactive hypothalmus, leading to less glutamate firing = less pleasure/emotions.

This study uses the HPA mathematical modelto suggest that external stressors applied for the right duration at the right time can REVERSE the low cortisol, oversensitive GR state! So stress yourself out just a little bit, and you might be able to paradoxically reverse HPA axis dysfunction! But figuring out what counts as enough "stress" and for how long is very difficult.

Another study analyzes the model and suggests GR antagonists can return one from this state to normal. Unfortunately RU-486 probably won't work for this because it doesn't enter the brain, and instead actually raises cortisol in the brain by blocking cortisol from crossing the blood-brain barrier. One would need to antagonize GR on the pituitary gland in the brain or somehow lower cortisol levels.

I should probably make a new thread on this to organize it better. But basically, we want to increase glutamate in the brain by fixing the HPA axis, if that is indeed a problem for you. Additionally, high serotonin or upregulated 5HT2A receptors could be a problem inhibiting glutamate.

What tests would be needed to find out which route to take? I'm on TEI currently but after a year or two I'd like to try other things.

 

[talkingant]

What tests would be needed to find out which route to take? I'm on TEI currently but after a year or two I'd like to try other things.

For PSSD that involves HPA axis dysfunction, you should check cortisol levels. Get AM and PM cortisol blood tests, as well as ACTH. TEI sometimes gives you adrenal gland extract in their supplements, which contains cortisol. So stay off that for a few days before getting cortisol blood tests.

If ACTH is normal but cortisol is low, you could be in a similar situation described in my post, which is that your hypothalmus is underactive, causing reduced glutamate levels. There are some ways that SSRIs could have caused this. If you find low cortisol, and you also have anhedonia as a primary symptom, then you probably have too low glutamate. As of right now, the only treatment we know of that can address this issue is psilocybin. And it probably isn't a cure but rather temporary relief. We are looking into other ways to address the HPA axis and glutamate.

Otherwise, you should get in contact with Mesolimbo on PSSDForum. He has a better understanding of the different types of PSSD. If you donate to his Patreon he will give you a personal evaluation right away, but you can also post in the forum and he will respond eventually.

 

[Aflac94]

For PSSD that involves HPA axis dysfunction, you should check cortisol levels. Get AM and PM cortisol blood tests, as well as ACTH. TEI sometimes gives you adrenal gland extract in their supplements, which contains cortisol. So stay off that for a few days before getting cortisol blood tests.

If ACTH is normal but cortisol is low, you could be in a similar situation described in my post, which is that your hypothalmus is underactive, causing reduced glutamate levels. There are some ways that SSRIs could have caused this. If you find low cortisol, and you also have anhedonia as a primary symptom, then you probably have too low glutamate. As of right now, the only treatment we know of that can address this issue is psilocybin. And it probably isn't a cure but rather temporary relief. We are looking into other ways to address the HPA axis and glutamate.

Otherwise, you should get in contact with Mesolimbo on PSSDForum. He has a better understanding of the different types of PSSD. If you donate to his Patreon he will give you a personal evaluation right away, but you can also post in the forum and he will respond eventually.

What you said above doesn’t make sense to me, hypothalamus makes CRH which stimulates anterior pituitary to make ACTH which stimulates adrenal glands to make Cortisol. So if hypothalamus was under functioning ACTH would be low and cortisol would be low. If ACTH is normal adrenal glands should be the problem.

 

[Astral kid]

For PSSD that involves HPA axis dysfunction, you should check cortisol levels. Get AM and PM cortisol blood tests, as well as ACTH. TEI sometimes gives you adrenal gland extract in their supplements, which contains cortisol. So stay off that for a few days before getting cortisol blood tests.

If ACTH is normal but cortisol is low, you could be in a similar situation described in my post, which is that your hypothalmus is underactive, causing reduced glutamate levels. There are some ways that SSRIs could have caused this. If you find low cortisol, and you also have anhedonia as a primary symptom, then you probably have too low glutamate. As of right now, the only treatment we know of that can address this issue is psilocybin. And it probably isn't a cure but rather temporary relief. We are looking into other ways to address the HPA axis and glutamate.

Otherwise, you should get in contact with Mesolimbo on PSSDForum. He has a better understanding of the different types of PSSD. If you donate to his Patreon he will give you a personal evaluation right away, but you can also post in the forum and he will respond eventually.

I guess you don't believe TEI can solve these sorts of issues right? I'll see what I'm like in a year or two. I do have anhedonia but it really isn't an issue, I don't really have any sexual sides anymore from my PSSD and working out all the time and sprints make me feel pretty good as is. I'm on the forum so I'll shoot him a message thanks for the reply bro.

 

[talkingant]

What you said above doesn’t make sense to me, hypothalamus makes CRH which stimulates anterior pituitary to make ACTH which stimulates adrenal glands to make Cortisol. So if hypothalamus was under functioning ACTH would be low and cortisol would be low. If ACTH is normal adrenal glands should be the problem.

There is a delay between ACTH release and cortisol release from the adrenal glands. Low cortisol can blunt its own production via negative feedback to the pituitary gland if the pituitary GR receptors are upregulated. For ex, ACTH starts to rise due to upstream stress response, cortisol starts to rise which activates hypersensitive pituitary GR. GR upregulates even more, dramatically lowering ACTH. This happens before the adrenal glands release all the cortisol they should have from the original ACTH spike. So during this delay, ACTH plummeted briefly, blunting the total amount of cortisol release. If GR didn't upregulate, ACTH wouldn't drop as much and the adrenals would release a more expected amount of cortisol during a stress response.

Keep in mind, I am just interpreting the mathematical model. I probably am not understanding it 100%. It is a complex differential equation that is hard to describe without math, and there are multiple feedback loops, so thinking "intuitively" about how the HPA axis works is not very accurate, unless you have good understanding of the differential equation. What the model authors prove however, is that there is a hypocortisol state characterized by upregulated GR on the pituitary, which lines up with what has been observed in some CFS and PTSD patients.

Regarding ACTH and cortisol blood levels, hypocortisol states can be seen with clinically low (out of range) cortisol, but not always out of range ACTH. For example in this CFS patient study. So my advice is, don't rule out this hypocortisol-upregulated GR theory if you find ACTH still in normal range while cortisol is low. To get the full picture you would really need a 24 hr chart of those with stress response tests.

Regarding the hypothalmus being "underactive," this is speculation. Since cortisol is dysregulated in this pituitary-GR-overexpressed state, and it is not clear whether hypothalamic GR behave the same way as pituitary GR, this could mean less excitory input to the hypothalmus. It could also mean the opposite, but either way there is probably not normal levels of hypothalmic excitation in this low cortisol state. Low hypothalmic excitation could have various effects on glutamate transmission and sex hormones, so PSSD symptoms appear to line up more with low hypothalmic excitation than high excitation.

Additionally SSRI's can upregulate GR, potentially putting the HPA axis in a stuck low cortisol state.

In a nutshell, this is just a working theory providing one possible explanation for what is happening to PSSD patients with low cortisol. In high cortisol cases, these systems are still involved but the dynamics make it complicated to predict what would happen. For the low cortisol case, we are lucky to have the mathematical models examine what happens in that case. The study authors should look into high cortisol situations as well for more insight.

 

[talkingant]

I guess you don't believe TEI can solve these sorts of issues right? I'll see what I'm like in a year or two. I do have anhedonia but it really isn't an issue, I don't really have any sexual sides anymore from my PSSD and working out all the time and sprints make me feel pretty good as is. I'm on the forum so I'll shoot him a message thanks for the reply bro.

TEI definitely does something to the HPA axis, but the science of mineral balances does not go as in depth as these mathematical models of the HPA axis and related neuroendocrinology. So it could help, but it is not based on the current leading science. Additionally, since no one really knows exactly what is going on with PSSD, TEI was not designed for it. If TEI can "reset" the HPA axis to a normal state, then that would help PSSD in this theory I am proposing. But we do not know how exactly how TEI programs effect the HPA axis, in light of these more accurate mathematical models.

 

[Helen]

TEI definitely does something to the HPA axis, but the science of mineral balances does not go as in depth as these mathematical models of the HPA axis and related neuroendocrinology. So it could help, but it is not based on the current leading science. Additionally, since no one really knows exactly what is going on with PSSD, TEI was not designed for it. If TEI can "reset" the HPA axis to a normal state, then that would help PSSD in this theory I am proposing. But we do not know how exactly how TEI programs effect the HPA axis, in light of these more accurate mathematical models.

the science of NB goes much further than all your math models, since they have a huge computer with all enzymes. and math model is limited and looks at one thing, TEI looks at all enzymes of the whole body at once. and has one of the biggest and well researched machine learning model

 

[Jamie]

the science of NB goes much further than all your math models, since they have a huge computer with all enzymes. and math model is limited and looks at one thing, TEI looks at all enzymes of the whole body at once. and has one of the biggest and well researched machine learning model

Are there some publications about their research? ML, ANN are getting more and more interest in modern medicine. It would be nice to look at what they found out

 

[Helen]

TEI definitely does something to the HPA axis, but the science of mineral balances does not go as in depth as these mathematical models of the HPA axis and related neuroendocrinology. So it could help, but it is not based on the current leading science. Additionally, since no one really knows exactly what is going on with PSSD, TEI was not designed for it. If TEI can "reset" the HPA axis to a normal state, then that would help PSSD in this theory I am proposing. But we do not know how exactly how TEI programs effect the HPA axis, in light of these more accurate mathematical models.

I think I understand PSSD pretty well. there is nothing to reset. there are no overexpressed receptors, It never happens this way.

PSSD is a simple zinc toxicity. and nothing else.

I said that a year ago. NO one listens



and in this case, ZINC increases GABA B.

that is ALL.


zinc blocks gaba a , this increases glutamate to gaba conversion. so total GABA level goes up.

this total GABA level acts on GABA B receptor. GABA B thru inositol phos phate increases intracelluar CALCIUM


progesterone goes up, cortisol is inhibited. histamine inhibited, estrogen inhibited,( low cannabinoids, low anandamide) low opiods - these are your emotions.

this is PSSD.

 

[Nina]

I think I understand PSSD pretty well. there is nothing to reset. there are no overexpressed receptors, It never happens this way.

PSSD is a simple zinc toxicity. and nothing else.

I said that a year ago. NO one listens



and in this case, ZINC increases GABA B.

that is ALL.


zinc blocks gaba a , this increases glutamate to gaba conversion. so total GABA level goes up.

this total GABA level acts on GABA B receptor. GABA B thru inositol phos phate increases intracelluar CALCIUM


progesterone goes up, cortisol is inhibited. histamine inhibited, estrogen inhibited,( low cannabinoids, low anandamide) low opiods - these are your emotions.

this is PSSD.

Would the same thing happen to non PSSD people taking excessively high doses zinc?

 

[Helen]

Would the same thing happen to non PSSD people taking excessively high doses zinc?

yes, this can easily happen to people just taking zinc.

so people can get PSSD PFS just from taking zinc. in some cases.

 

[Ingeno]

yes, this can easily happen to people just taking zinc.

so people can get PSSD PFS just from taking zinc. in some cases.

Can this zinc toxicity show up on the hair test, or can it be hidden as well? I have abused zinc in my teens and early twenties. I do have PSSD symptoms but zinc shows normal on hair test.

 

[RebelWithACause]

Can this zinc toxicity show up on the hair test, or can it be hidden as well? I have abused zinc in my teens and early twenties. I do have PSSD symptoms but zinc shows normal on hair test.

Fucking weird how many similarities are on this forums. I also abused zinc in early twenties before ever touching finasteride. Since it gave me mental clarity and energy after masturbating. Thought I was the only guy playing w/ minerals pre-fin.

 

[Ingeno]

Fucking weird how many similarities are on this forums. I also abused zinc in early twenties before ever touching finasteride. Since it gave me mental clarity and energy after masturbating. Thought I was the only guy playing w/ minerals pre-fin.

Yeah I know right. Reading everywhere that zinc increases testosterone, thinking it would be grear for bodybuilding. In the end is was probably a bad idea supplementing it without its co-factors or taking high dosages for long periods. Eventually I got really nauseous taking 25-50mg zinc.

 

[talkingant]

the science of NB goes much further than all your math models, since they have a huge computer with all enzymes. and math model is limited and looks at one thing, TEI looks at all enzymes of the whole body at once. and has one of the biggest and well researched machine learning model

The way we determine what theories are accurate is to test the model predictions against real world data. For example, can I tell TEI a patient's ACTH level, and TEI calculates what the patient's cortisol level will be? If TEI has a supercomputer simulation, they should be able to do this. Then, we can check the patient's actual cortisol level and see if it matches with what TEI predicted.

Scientists have done exactly this with HPA axis mathematical models. This study shows the model accurately predicted a patient's cortisol level from ACTH values.



If you can show me testable predictions from TEI, we can see how accurate TEI is compared to other models. This is how the scientific method works, after all.

PSSD is a simple zinc toxicity. and nothing else.

and in this case, ZINC increases GABA B.

that is ALL.

zinc blocks gaba a , this increases glutamate to gaba conversion. so total GABA level goes up.

this total GABA level acts on GABA B receptor. GABA B thru inositol phos phate increases intracelluar CALCIUM

progesterone goes up, cortisol is inhibited. histamine inhibited, estrogen inhibited,( low cannabinoids, low anandamide) low opiods - these are your emotions.

That's an interesting theory. How does an SSRI cause zinc toxicity? How does this zinc toxicity last for years after the SSRI? Why don't we see "post zinc syndrome" people? For the record I never took any zinc before getting PSSD.