Identifying relevant substances

[DrugsAreBad]

Background

The body is constantly striving to balance its levels of various substances by keeping them within certain bounds. For many substances, this balancing by up- and down regulation happens on a perceptible time scale of days to weeks and explains why the introduction of a substance has a certain short term effects and other long term effects.

There is no guarantee that the body will return to its previous state after the removal of a previously introduced substance, as illustrated by this forum. This indicates that the up- and down regulation is less than perfect.

Given that the same substance can have opposite effects on different people (like SJW making some people horny and others lose their libido), it follows that this less than perfect up- or down regulation can be either too high or too low. So, taking a substance can get us stuck in either a permanently upregulated or permanently downregulated state.

Let's say that PSSD/PSAD is caused by high cortisol levels[1], as indicated by TalkingAntColony. This would explain the positive short term effects of Ginkgo mentioned by Bunny[2], since Ginkgo apparently lowers cortisol levels[2] and why it stops working. It would also explain why people had long term have success on liquorice root, which raises cortisol levels[3], but short term worsening[5] on the same substance. I.e., raising cortisol levels may worsen symptoms but lead to an overcompansated downregulation over time.

Implications

So to actually find a cure, we need take something for a period of time long enough for an up- or downregulation of the relevant substance to take place. Bunny mentions twelve weeks before being permanently cured.[4]

But what about people who have taken a single dose of a substance? That's hardly long enough for up- or down regulation to take place.

Actually, it can be. For example, Reserpine irreversibly blocks VMAT, which takes the body weeks to replanish.[6] So even short term use, may cause a state to exist for several weeks, which is plenty of time for the body to adjust.

So whatever value we're looking to raise or lower, Corsitol or something else, how do we cause a permanent increase or decrease?

Unfortunataly since we don't know how each person is calibrated, we seem to have no way of predicting if introducing a substance will cause a non-sufficient downregulation leading to an increase, or an overcompensation leading to a decrease. So the best (or only) bet, seems to be to try substances that have some effect, for a long enough period of time that either an up- or downregulation takes place. (And yes, it's russian roulette.)

Summary

For each person, a substance that causes either a short term worsening or a short term improvement is the right way to a cure, but there is currently no way of predicting which. So when experimenting, we should try both substances that improve and worsen symptoms in the short term and evaluate them after at least a few weeks.

With that said, I'm off to experiment with substances that raise or lower Cortisol.

1. http://www.pssdforum.com/viewtopic.php?f=22&t=2295
2. http://www.pssdforum.com/viewtopic.php? ... 1&start=50
2. https://www.ncbi.nlm.nih.gov/pubmed/12369732
3. https://www.researchgate.net/publicatio ... _receptors
4. http://www.pssdforum.com/viewtopic.php? ... unny+cured
5. http://www.pssdforum.com/viewtopic.php? ... rice#p8733
6. https://en.wikipedia.org/wiki/Reserpine

[iull1k]

Hi! There is a good point about down/upregulation, it's roulette. I often see in researches how is expected to upregulate or downregulate something with a substance and the result is completly different, without any explanations. But i really have doubdts that the cause of PSSD is cortisol. Cortisol dysregulation is a cause of dysregulated HPTA Axis, it's a cascade of effects. And all substances that you wrote works with Androgens and Gaba. Licorice Root have serious impact on HPTA axis and Androgen Receptor. Inositol, more then this, is used for for PCOS or mentrual dysphoria/ pain, acneea. Guess why? It's a serious androgen modulator.

[Jaxx]

I like your initiative! Have you measured your cortisol (24h) in the past? Might be good to establish a baseline.

I found this PHD thesis on serotonin and cortisol I still need to read the full version, but it seems to offer a good introduction/overview
http://www.rug.nl/research/portal/files ... thesis.pdf

I dont think cortisol is the main cause for PSSD, but it is involved somehow. Looking at licorice root, which has effect on cortisol levels and seems to benefit several people here. The sexual effects (better erections) of it seem to diminish over time, at least for me.

There also seems a link to progesterone : Differential Effects of Chronic Antidepressant Treatment on Swim Stress- and Fluoxetine-Induced Secretion of Corticosterone and Progesterone
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3025615/

Although i am on parnate now, and this mighve changed my cortisol levels, i will try to get a 24h cortisol test. Will take another if i come off parnate to see if there are significant differences there.

[DrugsAreBad]

Thanks Jaxx. I haven't measured my cortisol levels, but I'll see if I can get it done and report if I have any relevant info.

[TalkingAnt]

If you want to try directly agonizing or antagonizing cortisol receptors (which could cause a feedback loop to change cortisol levels), you can try mifepristone (antagonist) or dexamethasone (agonist).