Attempting to cure/reverse my own PSSD

Post any data on Treatments and experimentation.
User avatar
Meso
Posts: 884
Joined: Tue Jan 22, 2019 3:00 pm
Contact:

Attempting to cure/reverse my own PSSD

Unread post by Meso »

I've been very stressed out in life recently due to an unforeseen financial trouble. I probably won't be able to afford the symptomatic regimen I'm currently on for more than a couple of months until I get my financial situation sorted out. So, I'm left with no choice but to attempt a cure/reversal in case the situation doesn't improve. I was thinking of taking a break from the forum and try to relax, but maybe it would be better to document my journey here, for better or for worse.

Now, my hypothesis is that SRI intake has caused 3 main deficits I named the "trial of evil". I discussed this in several other threads:
1- Glutamate release dysregulation leading to mesocorticolimbic pathway dysfunction and cognitive dysfunction, due to blunting of HPA axis and cortisol release (GR upregulation) as well as altered density of several serotonin receptor subtypes.

2- SSRI withdrawal-induced postsynaptic 5HT1A hypoactivation + presynaptic 5HT1A rebound supersensitivity.

3- Androgen (and possibly estrogen) receptor subsensitivity and dysregulation, leading to sex hormone resistance.

Here's how I'll address each point:
1- For GR downregulation, I would need an ACTH releaser or a corticosteroid. Since I'm against the latter, an ACTH releaser would be ideal. For this, I'll use Baclofen which would also cause a glutamate rebound on top of the cortisol release, potentially restoring long-term potentiation for the duration. As to addressing neurotrophic factors, I'll be taking Metformin which boosts BDNF and upregulates TrkB receptors. It raises SHBG but more on that later.

2- For presynaptic 5HT1A supersensitivity, the only way to "reverse" that would be through desensitization. For this to happen, I need a full agonist with a high intrinsic activity (near 100%). Initially, I thought Buspirone would be ideal but research is showing inconsistent results regarding downregulation. It's also a partial agonist at postsynaptic 5HT1A with low intrinsic activity, which beats the point. The only other full agonist is Vortioxetine, which is also an antagonist of several receptor subtypes (1B, 1D, 3, and 7). This profile would make it one of the most pro-glutamatergic antidepressant, perhaps this is why it's less associated with sexual dysfunction.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4241092/
https://www.ncbi.nlm.nih.gov/pubmed/29269186
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6146203/

Since I no longer believe in the SERT downregulation + presynaptic 5HT1A desensitization/decoupling theory, and I actually believe in the opposite (presynaptic 5HT1A supersensitivity + postsynaptic 5HT1A hypoactivation), for my type of PSSD I feel comfortable taking Vortioxetine for the sake of this experiment.

3. For sex hormone receptor sensitivity, increasing endogenous sex hormones would restore it. For this I'll be taking Mesterolone to bind with SHBG (including the excess from Metformin) and increasing my free testosterone level. If I feel that it's not enough, I may consider taking Clomiphene.

So, initial regimen looks like this:
- Baclofen: 25-50 mg. (ACTH release, GR downregulation, glutamate rebound)
- Vortioxetine: 5 mg. (Presynaptic 5HT1A desensitization, pro-glutamatergic)
- Metformin: 1000 mg XR. (BDNF boosting, TrkB upregulation)
- Mesterolone: 25-50 mg. (SHBG lowering, increasing free testosterone)

I'll be taking this for 3-6 months. Depending on how miserable it will make me feel. These drugs are about 50% cheaper than my symptomatic relief ones, so I can probably see this trial through, unless I need to add Clomiphene or Rasagiline.

As with trial-and-error, I could end up cured, or I could end up much worse than before. It's a risk I'm willing to take at the moment. If it works, I'll need to remain on a single drug to keep presynaptic 5HT1A from sensitizing again. Probably Vortioxetine, or if I find something else that's more selective, would be better, since Vortioxetine upregulates GR and I'm not sure Baclofen's ACTH release would be able to overpower that. We'll see. :shock:
Last edited by Meso on Thu May 02, 2019 7:00 am, edited 1 time in total.
Blog: Link 1
Q&A session 1: HTML
User avatar
Snake
Posts: 310
Joined: Thu May 03, 2018 1:45 pm
Contact:

Re: Attempting to cure/reverse my own PSSD

Unread post by Snake »

Go, let's destroy PSSD Mesolimbo! Good luck!

It's such a shame that in the US drugs and healthcare are soo expensive.
Finding a cure is only a matter of time! Never quit!
User avatar
AnhedonicApe
Posts: 289
Joined: Tue Apr 23, 2019 7:07 am
Contact:

Re: Attempting to cure/reverse my own PSSD

Unread post by AnhedonicApe »

Good luck man! Aren't you scared of the baclofen withdrawal?
User avatar
Meso
Posts: 884
Joined: Tue Jan 22, 2019 3:00 pm
Contact:

Re: Attempting to cure/reverse my own PSSD

Unread post by Meso »

AnhedonicApe wrote:Good luck man! Aren't you scared of the baclofen withdrawal?
Baclofen withdrawal isn't as severe as Phenibut withdrawal since the latter is a GABA-A agonist. I find that if I take a 2 days break each week from Baclofen, there isn't much withdrawal. There are patients on megadoses of Baclofen (intrathecal) and withdrawals usually aren't severe and there isn't a major tolerance problem, unlike with Phenibut.

I've taken my first dose of Vortioxetine and there's a significant worsening of all symptoms, except for cognitive ones (since it boosts cortical glutamatergic neurotranmission acutely, re: 5HT3/7 antagonism). Which means my hypothesis is correct regarding presynaptic 5HT1A receptors. Downregulation happens as soon as 3-7 days, so I expect this worsening to pass, hopefully with relief emerging over the next couple of months.
Blog: Link 1
Q&A session 1: HTML
User avatar
Snake
Posts: 310
Joined: Thu May 03, 2018 1:45 pm
Contact:

Re: Attempting to cure/reverse my own PSSD

Unread post by Snake »

I hope that baclofen withdrawal wouldn't be so severe too...
My psychiatrist didn't want to prescribe it to me because she said that she has bad experiences with patients and their baclofen addiction, one patient recently almost died, she said.
Finding a cure is only a matter of time! Never quit!
User avatar
Meso
Posts: 884
Joined: Tue Jan 22, 2019 3:00 pm
Contact:

Re: Attempting to cure/reverse my own PSSD

Unread post by Meso »

Snake wrote:I hope that baclofen withdrawal wouldn't be so severe too...
My psychiatrist didn't want to prescribe it to me because she said that she has bad experiences with patients and their baclofen addiction, one patient recently almost died, she said.
Remember to take breaks and keep the dose low. Baclofen abuse usually involves daily intake of 100+ mg.
Blog: Link 1
Q&A session 1: HTML
Jaxx
Posts: 974
Joined: Sat May 14, 2016 7:55 pm
Contact:

Re: Attempting to cure/reverse my own PSSD

Unread post by Jaxx »

We appreciate your updates alot, lets hope this will be a big step forward. It seems a quite different regime compared to the other cures here, but those also couldnt be replicated.
barbaar
Posts: 18
Joined: Tue Apr 16, 2019 6:20 am
Contact:

Re: Attempting to cure/reverse my own PSSD

Unread post by barbaar »

Good luck meso! Looking forward to your updates
Frog
Posts: 149
Joined: Sun Feb 24, 2019 2:37 pm
Contact:

Re: Attempting to cure/reverse my own PSSD

Unread post by Frog »

Good luck mate, hope it works out for you!
User avatar
dangerwood
Posts: 50
Joined: Wed Sep 26, 2018 9:09 am
Location: Australia
Contact:

Re: Attempting to cure/reverse my own PSSD

Unread post by dangerwood »

Good luck man, we are all behind you!

If you are one of those people who think no progress is being made with PSSD then honestly you are just pessimistic and will probably never recover. Rewind back just 1 year ago when meso wasn’t even on this forum, and think about all the work he has done since then. There will be many new forum members, new medications and new recovery stories in the next year as well that will help us get closer to defeating this shit.
We're all gonna make it brah
Post Reply

Who is online

Users browsing this forum: No registered users and 3 guests