PSSD/PFS/PAS - The P450 Enzymes - Possible Mechanism

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nicopickle
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PSSD/PFS/PAS - The P450 Enzymes - Possible Mechanism

Unread post by nicopickle »

Hello. I've had PAS/PSSD for 2 and a half years now. I've been trying to find a common mechanism between these drugs that could be tracked down to elicit similar symptoms from completely different mechanisms. I recently read a post about a girls story about getting PSSD, in her story, she mentioned that she tested her P450 enzymes for which drugs would work best for her, basically every drug had red flags saying she couldn't metabolize them. This post brought me to the PFS forum, and there have been people talking about these enzymes for 10+ years, and recently a user named spstriken talked about how he believes these enzymes are responsible for our symptoms, and I actually also agree.

Now I bet a lot of people wonder about the cases from a single dose of a drug, or very limited doses. This always confused me, especially with things like the SSRI causing gut dysbiosis. However the gut theory also comes into play in a way here, these P450 enzymes are most notably in the small intestine, and liver. They may seem like they are only good for absorbing drugs, however they are extremely important, even from a simple google search, you can find out that they are responsible for hormone, breakdown, and synthetization, they are also responsible for absorbing vitamin D, as well as a multitude of other things.

Now there along with all of the things they are responsible for, they are also needed to metabolize many things. I've always wondered why people stop responding to alcohol, and other substances when developing PSSD, well I think that its directly linked to the state of these enzymes. However I don't believe that there is any sort of damage to these enzymes, I think there is some sort of immune response, which is a protective mechanism when we are heavily dosing these drugs.

When I read all of these recovery stories, I was always so confused, you have people recovering from the most random substances, and a lot of the time, people are even cured by going back on the drug that caused the issues initially. I used to always skim past these posts until I really thought about it. One of my favorite recovery posts is by a user named "pete" on the PSSD forum. He initially got worse from trying to reinstate a dose of paxil, the drug that caused his issues, but when he decided to take a very low dose, then take a break, he began to improve.

My temporary recovery:

I had a temporary improvement from a fecal matter transplant a few months back, it even seemed to hold a bit of permanent improvement over time. But the interesting thing is when I began to get improvements. I initially did the FMT through enema for about two weeks, I didn't have much improvement, but I continued anyway as people have mentioned that you need to do many transplants to populate the microbiome. I implemented capsule FMT through the top down method, within 5 minutes of taking two capsules I noticed a pulsing in my brain, this was kind of frightening but also very intriguing. Something was happening, after about a day I began to get VERY tired, something that has been absent since this condition started. I woke up the next day feeling very optimistic, something in me had changed, over the next day all of my symptoms seemed to improve. I kept taking more and more capsules as I thought I was going to be cured within a month. After a day or two all of my improvements started to fade, and I developed these bumps all over my toes and feet that progressed as I continued to dose. These bumps are a sign of an immune response, and are prevalent in people with covid, usually called covid toes.

I continued to try and replicate this over a month continuing the FMT's. I was never able to replicate that experience... until I took a decent break from the FMT, I stopped for maybe a week or two then tried another dose, I became very tired, and felt my memories flowing through my brain, I felt high. At this time I continued FMT every few days to try and continue benefits, however everything would fade again, however I somehow got permanent improvement in libido from this FMT, which I later crashed to another FMT, which was accompanied by a night of restless leg syndrome, strange right?

I continued to try and understand exactly what happened here, why did such a low dose have such impact, but anything more or more often would completely void all improvements? I remember reading about what exactly accutane was a while back, 13-cis retinoic acid. It's basically what a human body makes vitamin A into, its the endogenous version of vitamin A. So this made me wonder, did I take a very small amount of accutane inside of the FMT? This made me very interested in reinstatement. about a week back I took a low dose of accutane, 3mg within an hour I felt something, I felt a sensation where my neck meets my brain, 5 minutes later I felt a tingling sensation in my genitals along with a tingling on the front right part of my neck. This was accompanied by an increase of my senses, I could feel the comfort of my blanket, and smelling increased. I could also take deep breaths effortlessly, something that has been difficult since this started. Over the rest of the day I felt my body more, like I was more aware of what my body was doing (hard to explain). The next day I woke up and I felt a little weird, I felt so in control of my body, like walking was so effortless, it felt normal to walk around, I felt like my IQ increased and I just felt normal in my body. I didn't notice anything else during this next day so I decided to take 10mg, this was definitely a mistake as I began to feel almost high initially, but over the day I felt worse, that night I had restless leg syndrome again, I even experienced DPDR as my hands would randomly feel like they weren't mine, and it has now been about a week since the dose, and I've began to get red bumps on my toes again.

I am currently waiting a while before dosing anything again as whenever I get these toes, things have literally no effect on me.

Conclusions:



Every case of PSSD-like symptoms can be traced back to these enzymes, along with the majority of recoveries are also based around having impact on these enzymes. There is no reason for people to get such drastic recoveries in such a short period of time if the cause was anything else. I don't believe any of us have any sort of damage, I think that these enzymes are just doing their job and protecting us from overdosing. I believe the way to recover is to basically take an incredibly small amount of certain supplements then stop, and wait. We need to show our body that these substances wont cause problems by introducing small amounts, and allowing the body to react accordingly.
lukejimmy
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Re: PSSD/PFS/PAS - The P450 Enzymes - Possible Mechanism

Unread post by lukejimmy »

Could you please send me the link of her story or at least the website it was on?

Her Genetic Results fit perfectly with my theory that we cannot metabolize SSRI's as would be expected given these studies: https://pubmed.ncbi.nlm.nih.gov/10755579/
https://pubmed.ncbi.nlm.nih.gov/9068197/ https://sci-hub.se/https://pubmed.ncbi. ... /10755579/ (full-text link of first Prozac study)
Last edited by lukejimmy on Mon Oct 03, 2022 10:17 am, edited 2 times in total.
HzeTmy
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Re: PSSD/PFS/PAS - The P450 Enzymes - Possible Mechanism

Unread post by HzeTmy »

Can't metabolize mean medicaments accumulated and left us with toxic permanent damage ?

or does it mean the ssri are still inside our bodies and waiting for P450 enzymes to be artifically injected ?
Last edited by HzeTmy on Sun Oct 02, 2022 1:19 pm, edited 1 time in total.
HzeTmy
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Re: PSSD/PFS/PAS - The P450 Enzymes - Possible Mechanism

Unread post by HzeTmy »

I was taking 1 year Gingko Biloba before antidepressants what also caused erectile problems at the end but ssris was the main killer of everything seems like Ginkgo Inhibits P450.

" The extraction, isolation and characterization of 29 natural products contained in Ginkgo biloba have been described, which we have now tested for their in-vitro capacity to inhibit the five major human cytochrome P450 (CYP) isoforms in human liver microsomes. "

From https://pubmed.ncbi.nlm.nih.gov/15285849/

Also interesting sexual dysfunction and p450 post :
https://pubmed.ncbi.nlm.nih.gov/33166302/
lukejimmy
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Re: PSSD/PFS/PAS - The P450 Enzymes - Possible Mechanism

Unread post by lukejimmy »

HzeTmy wrote: Sun Oct 02, 2022 12:58 pm Can't metabolize mean medicaments accumulated and left us with toxic permanent damage ?

or does it mean the ssri are still inside our bodies and waiting for P450 enzymes to be artifically injected ?

Even better, these medications (SSRI/Dutasteride/Fluoroquinolones) are quite literally known Forever Chemical Perfluoroalkyl Substances that via https://en.wikipedia.org/wiki/Biomagnification cannot be metabolized and therefore excreted from the body, leaving Persistent Toxicity but NOT permanent damage.

Like other PFAS there are known Detoxification Protocols, one being Blood Donations but this is IMMORAL because you will be giving TOXIC BLOOD to PEOPLE IN NEED. There are OTHER WAYS, Glutethimide is a CYP2D6 Inducer that would increase Fluoxetine Metabolism and Betamethasone has been shown to increase Fluoxetine Metabolism.

As for Artificial P450 Enzyme Injections that is Experimental Gene Therapy you are talking about, sounds VERY Risky and unnecessary seeing as their would be much safer Detoxification Protocols that we already are aware of like the above mentioned ^.
Last edited by lukejimmy on Mon Oct 03, 2022 3:04 am, edited 1 time in total.
Darman
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Re: PSSD/PFS/PAS - The P450 Enzymes - Possible Mechanism

Unread post by Darman »

Ok this is a great theory. What can we do to pursue it?
lukejimmy
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Re: PSSD/PFS/PAS - The P450 Enzymes - Possible Mechanism

Unread post by lukejimmy »

HzeTmy wrote: Sun Oct 02, 2022 1:07 pm I was taking 1 year Gingko Biloba before antidepressants what also caused erectile problems at the end but ssris was the main killer of everything seems like Ginkgo Inhibits P450.

" The extraction, isolation and characterization of 29 natural products contained in Ginkgo biloba have been described, which we have now tested for their in-vitro capacity to inhibit the five major human cytochrome P450 (CYP) isoforms in human liver microsomes. "

From https://pubmed.ncbi.nlm.nih.gov/15285849/

Also interesting sexual dysfunction and p450 post :
https://pubmed.ncbi.nlm.nih.gov/33166302/
Yes but Gingko Bilboa has been used for Millenia+ and is Naturally occurring plant medicine, not a Synthetic Fluorinated Chemical (fluorine (F)) that isn't found in Nature, nor found in Evolutionary History, which is why these Substances have no ability to undergo Detoxification and Elimination from the Human Body or Biological Organisms as a whole.
PFAS were created out of the Manhattan Project as Fluorine is used to create Nuclear Bombs, with the production of these Nukes generating Fluoride as a byproduct, with this byproduct infamously being intentionally put in our Water Supply despite being sourced for the manufacture of Nuclear Weapons and still is: https://www.youtube.com/watch?v=7r0c_kfdwQU

Gingko is easily eliminated from the body though natural genetic mechanisms.
Which is why there is no Post-Gingko Bilboa Syndrome or 100'000's of sufferers reporting persistent post-Gingko Side-Effects Internationally, as opposed to these PFAS "Medications".
HzeTmy
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Re: PSSD/PFS/PAS - The P450 Enzymes - Possible Mechanism

Unread post by HzeTmy »

So the cure is, find how your antidepressants or antipsychotics are metabolized be it p450 or CYP2D6 or others. Then find a medication or herb which induces that enzyme and try to supplement it to detoxify the drugs out ? Is this correct lukejimmy ?

For example google says St. Johns Wort is a CYP3A4 inducer could mean why some people get a recovery to a certain degree on St. Johns Wort ... Hmm
HzeTmy
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Re: PSSD/PFS/PAS - The P450 Enzymes - Possible Mechanism

Unread post by HzeTmy »

One page says Ginkgo inhibit other say induce p450 activity :(

https://pubmed.ncbi.nlm.nih.gov/15794086/
lukejimmy
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Re: PSSD/PFS/PAS - The P450 Enzymes - Possible Mechanism

Unread post by lukejimmy »

HzeTmy wrote: Mon Oct 03, 2022 10:48 am So the cure is, find how your antidepressants or antipsychotics are metabolized be it p450 or CYP2D6 or others. Then find a medication or herb which induces that enzyme and try to supplement it to detoxify the drugs out ? Is this correct lukejimmy ?

For example google says St. Johns Wort is a CYP3A4 inducer could mean why some people get a recovery to a certain degree on St. Johns Wort ... Hmm
What SSRI did you take? It is very difficult to find a CYP2D6 Inducer, with Glutethimide being the only real CYP2D6 Inducer I can find.
Glutethimide was Withdrawn from the market and manufacture discontinued Ofc.
The only problem is if you have a CYP2D6 genetic deficiency as was the case in these before mentioned studies: https://sci-hub.se/https://pubmed.ncbi. ... /10755579/, https://pubmed.ncbi.nlm.nih.gov/10755579/, then I'm assuming you won't be able to Induce CYP2D6 regardless?
It still would be worth trying as you can find recoveries on the PFS/PSSD Forums from taking St Johns Wort like you said, Antibiotics like Rifampicin/Rifampin and Dexamethasone which are all potent Cyp3a4 inducers.

If you get a blood test for the drug that caused your PSSD and it's proven to be detected, the best option would be to get rid of that blood via Therapeutic Phlebotomy (professional bloodletting) rather then giving an unethical blood donation and risking giving PSSD to someone in need. This is what people with high levels of other PFAS such as Firefighters have done and it's proven to lower the levels of Forever Chemicals in the body.
HzeTmy wrote: Mon Oct 03, 2022 11:06 am One page says Ginkgo inhibit other say induce p450 activity :(

https://pubmed.ncbi.nlm.nih.gov/15794086/
I'm assuming it would have to be a Potent Inducer and which particular CYP enzyme in your trying to induce is important. The Gingko Inhibition was in-vitro (artificial environment...test tube) using 29 individually extracted Gingko Isolates , the Gingko Induction study was in-vivo (living rat subjects) and used 2 Gingko Extracts (whole extracts as opposed to isolates?) that induced CYP indepedent of proanthocyanidin levels
Last edited by lukejimmy on Tue Oct 04, 2022 2:46 am, edited 1 time in total.
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