New study reveals the epigenetic effects of Citalopram

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AnhedonicApe
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Re: New study reveals the epigenetic effects of Citalopram

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nasibi wrote:
AnhedonicApe wrote:I think this is a must read too: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864977/
I think it might be helpful if you could get Antonei Csoka also involved as he is the leading researcher in this whole PSSD and DNA methylation thing. The two studies I pm'd you about were both done by Csoka et al.
Yes i will do that. I have read ur links, i am not really convinced it will do it's work in non proliferating cells. I am also not convinced it will do not. I will try contacting Csoka and the other docs to see what they have to say about it, and if maybe they have other options.
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nasibi
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Re: New study reveals the epigenetic effects of Citalopram

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@AnhedonicApe

I agree. The data is indecisive over whether drugs like 5-Aza can be effective in non-proliferating cells or not. But I don't think there are any better options, at least for now.
Death is not the greatest loss in life. The greatest loss is what dies inside us while we live. :(
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AnhedonicApe
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Re: New study reveals the epigenetic effects of Citalopram

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nasibi wrote:@AnhedonicApe

I agree. The data is indecisive over whether drugs like 5-Aza can be effective in non-proliferating cells or not. But I don't think there are any better options, at least for now.
Yeah it's better then nothing. They know now that the hippocampus does divide cells. It may have effect there. How hard have u researched if there may be other substances or ways to demethylate non-proliferating cells. I will try to come in contact with Csoka, maybe he knows something.
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nasibi
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Re: New study reveals the epigenetic effects of Citalopram

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AnhedonicApe wrote:
nasibi wrote:@AnhedonicApe

I agree. The data is indecisive over whether drugs like 5-Aza can be effective in non-proliferating cells or not. But I don't think there are any better options, at least for now.
Yeah it's better then nothing. They know now that the hippocampus does divide cells. It may have effect there. How hard have u researched if there may be other substances or ways to demethylate non-proliferating cells. I will try to come in contact with Csoka, maybe he knows something.
The studies I cited all suggest that it can work in non-proliferating cells. And it is not limitted to hippocampal cells.
Death is not the greatest loss in life. The greatest loss is what dies inside us while we live. :(
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AnhedonicApe
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Re: New study reveals the epigenetic effects of Citalopram

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nasibi wrote:
AnhedonicApe wrote:
nasibi wrote:@AnhedonicApe

I agree. The data is indecisive over whether drugs like 5-Aza can be effective in non-proliferating cells or not. But I don't think there are any better options, at least for now.
Yeah it's better then nothing. They know now that the hippocampus does divide cells. It may have effect there. How hard have u researched if there may be other substances or ways to demethylate non-proliferating cells. I will try to come in contact with Csoka, maybe he knows something.
The studies I cited all suggest that it can work in non-proliferating cells. And it is not limitted to hippocampal cells.
yes, it's worth trying, but I am less convinced then I was. If there is no other way in demethylating non-proliferating cells, this will be our only go to.
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nasibi
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Re: New study reveals the epigenetic effects of Citalopram

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As I said the data is inconclusive but to say that it is better than nothing would be downplaying it too much. It can go either way; too many variables to account for. I think we will only know when we try it ourselves. There are other drugs under development like MG98, SGI-1027 and RG108, but nothing as good as Aza/Deci yet.
Death is not the greatest loss in life. The greatest loss is what dies inside us while we live. :(
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AnhedonicApe
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Re: New study reveals the epigenetic effects of Citalopram

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nasibi wrote:As I said the data is inconclusive but to say that it is better than nothing would be downplaying it too much. It can go either way; too many variables to account for. I think we will only know when we try it ourselves. There are other drugs under development like MG98, SGI-1027 and RG108, but nothing as good as Aza/Deci yet.
I sometimes tend to read stuff a bit too fast. Took more time now and I agree, saying that it's better than nothing is not doing it justice.
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Re: New study reveals the epigenetic effects of Citalopram

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If I had the chance I would try Aza/Decitabine + HDACi.
Or even split-test them with and without HDACi.
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Re: New study reveals the epigenetic effects of Citalopram

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succubus76 wrote:
taarn wrote:I'm very convinced our issues stem from epigenetic disruption. However our current options are very limited to revert back this altered gene regulation/expression.
Mmhhh Yea, is weird, Ive seen people react opposotely from benzos and alcoho after psych drugs. However, people that never touch ssris, never seems to have this problem. And is not a tolerance issue. Tolerance and react adversile are different things.
taarn wrote: "It incorporates into DNA strands upon replication, and then when DNA methyltransferases (DNMTs) such as DNMT1, are engaged to bind the DNA and to replicate the methylation to the daughter strand, DNMTs are bound to decitabine irreversibly and cannot disengage. Therefore, the action of decitabine is division-dependant, meaning the cells have to divide in order for the pharmaceutical to act."

^ This appliest to Decitabine and Azacitidine. These meds need cell division to prevent methylation. Most cells in the adult brain don't divide. However these can have effect throughout your body as well, I would say most likely help people with ED issues, for example.
Yeah, they could help a bit, but as you said, the root problem is directly in the Brain, because people report a less genital anestesia after dopaminergics (rasaline, Wellbutrin, meth, cocaine, etc) whitout pssd these meds helps for libido anyways, and since erogenous sensation is restored somewhat after dopaminergics, lets me to believe our problem in part is dopamine innhibition
I believe my main problem is dopaminergic understimulation in the Mesolimbic pathway. I surely have serious issues around the NAcc, not enough glutamatergic excitation is likely involved as well. My HPA reactivity also sucks, I lost stress response almost completely, and nothing can excite me anymore.
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AnhedonicApe
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Re: New study reveals the epigenetic effects of Citalopram

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Hi @AnhedonicApe

It’s very interesting you’re going to trial this, but I must point out this is not to be taken lightly. To be even potentially effective, which we certainly cannot say it will be, you would likely need to be using this drug for a considerable time.

To provide context as I am not sure how familiar you are with epigenetics, methylation modifies chromatin and thus alters the access of proteins that bind to DNA. Methylation is a repressive modification that can be practically permanent as it is “copied” upon cell division by methyltransferase enzyme DNMT1, while the enzymed DMT3a and 3b establish new methylation. The base 5-methylcytosine is formed through the attachment of a methyl group to the 5th position of the cytosine ring in a CpG dinucleotide. More methylation in a CpG island means a more repressed gene - a “dimmer switch” if you like. Methylation is by its very nature a question of degrees, and provides compelling explanation for the vast difference in affected sites and severities between patients (e.g. why some have a functional impairment like anesthesia while others will experience severe atrophy), and why additional persistent symptoms develop in PFS/PSSD patients following further endocrine disruption.

Proven significant epigenetic differences in pfs patients with genital pain and atrophy (Di Loreto 2014) were averagely 5 years after cessation, and this would rule out transient modifications in severe cases. Traish’s 2018 paper, The Post-finasteride Syndrome: Clinical Manifestation of Drug-Induced Epigenetics Due to Endocrine Disruption 1, discusses this finding.

During cell division and replication, DNMT1 maintains existing methylation, and is thus the target of Decitabine. Decitabine’s relevant action is the inhibition of DMNT1, and the result is a reduced maintenance of existing methylation. To be clear, methylation is crucially important in like…not being a pile of soup…and 80% of mammalian CpG islands are methylated. This is very important to cell differentiation. The effects of inhibition are more significant in the frequent application of cancer, as cancer cells divide much faster than other somatic cells, so are vulnerable to the interruption of DNMT1. To use such a thing to address deleteriously methylated loci in somatic cells, it remains to be seen whether something this nonspecific could be taken for a long enough duration without adverse effects in the rest of the organism. It is also important to consider that adult neurons do not divide. Although DNMT enzymes are expressed in postmiotic neurons, it is not yet clear exactly how they mechanistically regulate neuronal transcription.

I hope that helps you make your decision, and I wish you luck if you go ahead with it. Please keep us informed if so.



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