Epigenetics

[sjv16477]

In my opinion no one actually tried this treatment. He has not posted any update.

[Bigmum]

Mahmur had positive response with EGCG

[Glitch]

In my opinion no one actually tried this treatment. He has not posted any update.

So that guy wrote out all that shit and then just disappeared? That's bizarre. Well, I plan on trying some of this stuff soon.

[Kk88]

I've been reading more about this. I understand the very basics of what epigenetics is about and that some substances can give gene expression plasticity. What I don't understand is how it's suggested we turn this to tackle pssd - what we then do to ensure that this plasticity allows us to return to our previous state. Do we have to take something like curcumin to induce plasticity and then another thing to make the chances we want? Sorry. I've tried to read several articles but I can't do it

[Glitch]

I would assume that plasticity would encourage gene expression to go back to normal by itself but I actually have no idea. Genetics are incredibly complicated so we could really use more people that have an education in it. I doubt you would have to take something else besides the supplements that increase plasticity as far as that concept goes. I dunno though.

[Whalefallen]

Hey, just to add to the list of naturally occurring HDAC inhibitors (i.e. compounds that increase the plasticity of the epigenome):
-broccoli/sulforaphane
-ketone bodies (endogenous, created during fasting and keto diets and by eating coconut oil)
-black seed oil/thymoquinone (apparently a quite powerful one, though BSO is pretty serotonergic so you might want to be careful — I just had mild/moderate serotonin syndrome from combining BSO and 300 mg l-theanine, but I seem to have become extraordinarily sensitive to SS after my first time getting it, which is also what gave me PSSD)
-sodium butyrate (endogenous, created by gut bacteria when fed resistant starch such as cold potatoes and plaintains)

I don't really understand the difference between the various types of HDACi, but HDAC2 has been mentioned previously in the context of PSSD, right? Depending on the HDAC type they hit, some inhibitors may be much more useful than others.

Anyway, as long as no other substances are actively influencing the body at the time, I believe HDAC inhibition causes the affected parts of the epigenome to "reset", revert back to factory settings, so to speak. At least that's how I believe they work for addiction cessation — with no active reason for the change to remain, the change is undone, the speed of which depends on the power of the HDAC inhibitor. Though with fear extinction, you need to actively expose yourself to triggers for the fear reduction to take hold, but with the persistent/lingering effects of substances such as narcotics, you just need to take the HDAC inhibitor. I could be wrong though, I have no background in this stuff, just learned a little about it while looking for ways to facilitate fear extinction. There's a user on Reddit and Longecity named musicman4534 who's written and compiled a lot of information about HDAC inhibitors for the nootropic community. Here's a really interesting article of his: https://www.reddit.com/r/Nootropics/com ... rs_geared/

Disclaimer: My symptoms were caused by six months of daily supplementation of too large ashwagandha doses. I'm not sure how similar or dissimilar it is to true PSSD, but it also seems to have something to do with spinal serotonin receptors getting "stuck" in an unfavorable mode.

I have taken the pharmaceutical-grade pan-HDAC inhibitor vorinostat three times in smallish doses in order to erase conditioned fear. During this period, I was taking ashwagandha every night (so there was probably a build up of it in my system — I'd get pretty strong rebound anxiety and heart palpitations if I forgot to take it one night), but I thought that as long as I don't take ashwagandha while the vorinostat is active (about 4 hours), there would be no problem. Well, all three times just ended up giving me anxiety rather than removing any, followed by a night of heart palpitations. This could be just a side effect of the vorinostat, of course, but what I found interesting was that the symptoms were pretty much identical to a more intense form of the rebound anxiety that I would get whenever I quit ashwagandha without any taper! Heart palpitations, cortisol-ish feeling, but also the disappearance of the side effects I would get on ashwagandha, including, I believe, (though I took little notice of it at the time) the sexual impairment.

Anyway, so my suspicion is that the vorinostat instantly cancelled the built-up effect of the ashwagandha, hurling me head first into rebound anxiety and resetting my epigenome towards it default state, figuratively pruning my epigenome of the "stored" effect of the ashwagandha. Every time this happened, I started back up on the ashwagandha instantly again though, which in retrospect might have caused me to develop my subsequent sensitivity to ashwagandha and serotonergic substances in general. The idea, then, is that repeating that "purge" of the epigenome might remove the lingering sexual dysfunction.

I feel as though this could have implications for PSSD? Thinking of trying vorinostat again in the future to see if it helps.

[nasibi]

Ketogenic diet also induces epigenetic changes. Don't know if it is going to be of any good for PSSD symptoms.

[Ghost]

Topics Merged 8/8/17

[Luis Fernando Lopez]

Epigenetic change has occured within all of us, the evidence is pretty clear, isotretinoin (Accutane) alters epigenetic homeostasis through indirect mechanisms. Epigenetic side-effects may persist after discontinuation. Even more scary is that with more chronic exposure, cells adapt by an unknown hypothetical process that results in permanent modification to DNA methylation and chromatin structures, leading to enduring alteration of a given epigenetic network.
https://www.ncbi.nlm.nih.gov/m/pubmed/19501473/

[marsupial]

Valproate is said to induce activ demethylation and neuroplasticity