PSSD in 2024 and beyond: Meso's thoughts

[Meso]

Hey guys and gals!

Please share this with others:
Thanks for being by my side all these years. I really appreciate your support.

I remember the old days 3-4 years ago when the only theory about PSSD was 5HT1A autoreceptor desensitization and some abnormal SNPs and random trials. We have come a long way since then. My thoughts for the future of PSSD are:
1- FMT, FMT, FMT. And then some more FMT.
2- Ibogaine, two deep trips.
3- Metformin (MUST be the XR version)
4- Hormones (E2 + AAS)
5- Daily Psilocybin low dose.
6- rTMS: normally prescribed one to the left DLPFC **PLUS** intermittent theta burst to the right DLPFC.
7- Epigenetic modification. Especially TET1 upregulation.
8- If all things fail, then deep brain stimulation (DBS) or even ECT if truly desperate (very bad idea, but there is that for a last-ditch one).

Indeed, we have come a long way. My theoretical work on PSSD is my crowning achievement and I'm proud of it. Unfortunately, I may not be able to finalize the 2nd study on PSSD due to life circumstances. Perhaps one day the puzzle would be solved. Cheers!

[Meso]

Remember, remember!!

The microbial alterations triggered by PFS are THE EXACT same as those triggered by PSSD. Same strains, down to the letter.

You can have gut dysbiosis without having any gut issues. That's why it's essential to get gut microbiome test carried out.

Antidepressants alter the gut microbiota extensively during treatment and then especially so upon withdrawal.

This causes leaky gut (loss of tight-junctions integrity) -> autoimmune reaction against normal body proteins (AND receptors) - > loss of blood brain barrier integrity - > microglia and astrocytes activation - > cytokine storm - > excessive tonic glutamate release - > neuroinflammation and neurotoxicity - > direct blockade of dopamine receptors by specific cytokines - > malaise, fatigue, bedridden - > further autoimmunity (vicious cycle) - > prostatitis and whole-body low grade inflammation.

[ksv]

Why must metformin be xr version?

Thank you, I love your content but please be more active in your discord. so many people suffering

[Impermanence]

Thank you for post.
Unfortunately no one know what happen in PSSD, everything is just hypothesis.
Today we are not able to relieve PSSD, neither to cure it.
My unique advice would be no to follow to much advises. I got really worse with some recommandations (Ginseng).
I think the more secure is to look how other people react. This is more safe and smart than following biological speculation. (Saying this I'm scientist... But PSSD is so complex that today any advice would be a scam)

[Meso]

Why must metformin be xr version?

Thank you, I love your content but please be more active in your discord. so many people suffering

Thanks! I wasn't able to work much on the server after getting long covid and multiple sclerosis. But I intend to make a comeback. I have new options for PSSD treatment and some of my patients got much better on them. I intend to write an article on those options and explain the neuropharmacology behind them.

As for the Metformin, it increases akkermansia muciniphila within the gut microbiome. This strain protects the gut walls from becoming leaky. XR version increases exposure.

[Determined-Mind]

Thank you for the good news and I'm sorry to hear that you have multiple sclerosis.

In 2021 you created the thread "Symptoms and their specific treatments", I'd be curious to read you about it today, especially about the lack of pleasure sensations (physical anhedonia) on the genital area, breasts and the rest of the body (arms, belly, thighs, etc).

For emotional anhedonia to normally pleasurable activities, I'm surprised that at the time you wrote that the best treatments were Dexetrine or Methylphenidate.

Other drugs have been shown to improve anhedonia in the scientific literature.

These include
- bupropion
- aripiprazone (low dose < 5 mg)
- vortioxetine
- ketamine

But we have to be careful, because sometimes they misjudge anhedonia.

For example, the drug Auvelity (bupropion+dextromethorphan) is supposed to improve anhedonia, but when we look more closely at how they measure anhedonia, we see that their criteria are completely irrelevant : https://www.axsome.com/publications/ASC ... .25.22.pdf

Anhedonia can exist independently of sadness or cognitive attention disorders. These are different processes, so it makes no sense to include them when considering whether anhedonia is improved...

[Extremaduro]

So dxm and nalt?

[Titeuf]

Why must metformin be xr version?

Thank you, I love your content but please be more active in your discord. so many people suffering

Thanks! I wasn't able to work much on the server after getting long covid and multiple sclerosis. But I intend to make a comeback. I have new options for PSSD treatment and some of my patients got much better on them. I intend to write an article on those options and explain the neuropharmacology behind them.

As for the Metformin, it increases akkermansia muciniphila within the gut microbiome. This strain protects the gut walls from becoming leaky. XR version increases exposure.

Here in Belgium, the Metagenics laboratory markets a new probiotic supplement "Bactiol complete" with akkermansia muciniphila but unfortunately pasteurized so it is impossible for it to reproduce in the intestine, they added bifidobacterium lactis b-420 because according to studies it promotes multiplication of akkermansia muciniphila. Very expensive and as akkermansia was pasteurized I didn't buy it because for me it's money thrown down the toilet bowl.

what do you think of Lithium Carbonate or adderall or methylphenidate?

A year and a half ago, I had an antibiotic treatment for a tooth, Clindamycin (Dalacin) and I noticed improvements apart from the diarrhea but it was not really disturbing because I am constipated 365 days a year. Normally, I feel like my intestines aren't working or are slow. My digestion is slowed down enormously. Example, I eat at 4, 5 or 6 o'clock in the evening and at midnight or 1 o'clock in the morning, I have the feeling that my stomach is as full as when I finished eating. Heaviness, bloating, the stomach does not deflate, my sleep is slow to come, headaches and palpitations. Also when I don't empty my descending colon, sigmoid and rectum, I get sciatica. Constipation exacerbates overactive bladder, et cetera et cetera.

With Clindamycin, most symptoms disappeared or improved for several months. I had this treatment for 1 month. My digestion suddenly became fast, I felt my intestines working, clear sensations of having to go to the toilet, my sleep was of better quality. My libido, sensations and arousal improved, my stomach deflated.
Not long ago, I discovered that Clindamycin acts on the chollinergic system by increasing the secretion of acetylcholine and acting on nicotinic receptors. Which apparently had the effect of increasing your vagal tone. So better communication between the lower abdomen and the brain. In any case, I no longer had the feeling of being disconnected from my lower body.

A cholinergic treatment as for Parkinson's disease (a study shows positive effects on Parkinson's symptoms) or an acetylcholinesterase inhibitor would certainly have positive effects.
The only problem with Clindamycin is the diarrhea it causes and weight loss, being prescribed an off-label treatment for Parkinson's.
Like many, cigarettes, coffee or even THC no longer cause effects on the chollinergic system.

sorry if there is an error in the translation. I speak French.

Is there a medication that is easier to prescribe than "clindamycin" or "a treatment for Parkinson's" to increase bowel movements via the chollinergic system to evacuate bad bacteria more quickly which have time to proliferate because of constipation knowing that cigarettes or coffee no longer do anything to me?

Only by reintroducing escitalopram does coffee activate my intestines, otherwise nothing.
I don't really know why but since the second escitalopram treatment, when I stop it my digestive system gets worse each time. bupropion aggravates the problem, mirtazapine also and gives me the burning sensation certainly due to these anticollinergic effects, vortioxetine no improvement.
I can no longer live with these symptoms every day. I would rather have diarrhea than constipation.. I'm afraid to eat. Or is there a bacterial strain that promotes diarrhea or increases contractions?