excess serotonin

The serotonin transporter (SERT) is a key regulatory molecule in serotonergic transmission implicated in numerous biological processes relevant to human disorders. Recently, it was shown that SERT expression is controlled by miR-16 in mouse brain. Here, we show that SERT expression is regulated additionally by miR-15a as well as miR-16 in human and rat tissues.
anyone understand MIR - 16 and MIR-15a ? Will speeding or slowing down those increase SERT?
https://academic.oup.com/ijnp/article/16/3/621/650451

progesterone regulates?
https://www.ncbi.nlm.nih.gov/pubmed/22583478

Farshad wrote:The serotonin transporter (SERT) is a key regulatory molecule in serotonergic transmission implicated in numerous biological processes relevant to human disorders. Recently, it was shown that SERT expression is controlled by miR-16 in mouse brain. Here, we show that SERT expression is regulated additionally by miR-15a as well as miR-16 in human and rat tissues.
anyone understand MIR - 16 and MIR-15a ? Will speeding or slowing down those increase SERT?
https://academic.oup.com/ijnp/article/16/3/621/650451

progesterone regulates?
https://www.ncbi.nlm.nih.gov/pubmed/22583478

got another SNP  serotonin related
rs4570625

Yeah, its kind of difficult to make predictions/assertions based on this. We have NO IDEA how to regulate miR-16 and 15a for example. We have a marginal idea on hormonal influence but no practical/plausible methods to deal with them.

So I don't want to make any assumptions about them.

What we CAN DO is work on what we already know is RELEVANT.

That would be...
Things that raise SERT, as spoken before, Berberine, Evodiamine, Forskolin. These are evidence-based "treatments" for serotonin-related issues. Dosage is important, though.
Inositol is a constituent in some programs but unfortunately is VERY MUCH SO hit-or-miss.
St.John's Wort has confounding principles in the bark and can be too unpredictable to try, though may be helpful for Copper and DBH excess.

Yes im just waiting for the sert activators to arrive hopefully sometime this week..
What dosage would I need to use for them? I ordered  4  of the sert activators You mentioned on the article you made (skipped zinc).

Farshad wrote:Yes im just waiting for the sert activators to arrive hopefully sometime this week..
What dosage would I need to use for them? I ordered  4  of the sert activators You mentioned on the article you made (skipped zinc).

Doses on the bottle, to start. No need to go overboard!

What are the  serotonin autoreceptors? Are they there to make sure there is not too much serotonin?
Someone said If I  have  a defective MAO enzymes or SERT   increasing expression of them isn't going to help,is that true?.

Im hoping the sert activators arrives on friday

(edit) wont be coming until next week

Farshad wrote:What are the  serotonin autoreceptors? Are they there to make sure there is not too much serotonin?
Someone said If I  have  a defective MAO enzymes or SERT   increasing expression of them isn't going to help,is that true?.

Im hoping the sert activators arrives on friday

The "autoreceptors" tell the neuron to stop causing serotonin release, those would be 5-HT1A,1B and 1D primarily, but each of those receptors also has "other side" which would be heteroreceptors, primarily, and post-synaptic actions of which are quite opposite.

In regards to the other question, if you have "defective MAO" or SERT, then you would not achieve permanent benefit from SERT activators, but on the molecular level, may obtain some benefit in the short-run. As you continue taking the supplements. Unfortunately, there is nothing you can do at this point in time to permanently alter those proteins.

Which is why I really think Metergoline or another serotonin antagonist would/should be enough - if the correct dosage was used, because it overrides the need for direct depletion or other strategies.

Area-1255 wrote:

Farshad wrote:What are the  serotonin autoreceptors? Are they there to make sure there is not too much serotonin?
Someone said If I  have  a defective MAO enzymes or SERT   increasing expression of them isn't going to help,is that true?.

Im hoping the sert activators arrives on friday

The "autoreceptors" tell the neuron to stop causing serotonin release, those would be 5-HT1A,1B and 1D primarily, but each of those receptors also has "other side" which would be heteroreceptors, primarily, and post-synaptic actions of which are quite opposite.

In regards to the other question, if you have "defective MAO" or SERT, then you would not achieve permanent benefit from SERT activators, but on the molecular level, may obtain some benefit in the short-run. As you continue taking the supplements. Unfortunately, there is nothing you can do at this point in time to permanently alter those proteins.

Which is why I really think Metergoline or another serotonin antagonist would/should be enough - if the correct dosage was used, because it overrides the need for direct depletion or other strategies.

I can just take the sert activators for the rest of my life to keep benefit? I dont mind that.

and the metergoline wouldnt I also need to stay on it forever to keep the benefit ?

Farshad wrote:

Area-1255 wrote:

Farshad wrote:What are the  serotonin autoreceptors? Are they there to make sure there is not too much serotonin?
Someone said If I  have  a defective MAO enzymes or SERT   increasing expression of them isn't going to help,is that true?.

Im hoping the sert activators arrives on friday

The "autoreceptors" tell the neuron to stop causing serotonin release, those would be 5-HT1A,1B and 1D primarily, but each of those receptors also has "other side" which would be heteroreceptors, primarily, and post-synaptic actions of which are quite opposite.

In regards to the other question, if you have "defective MAO" or SERT, then you would not achieve permanent benefit from SERT activators, but on the molecular level, may obtain some benefit in the short-run. As you continue taking the supplements. Unfortunately, there is nothing you can do at this point in time to permanently alter those proteins.

Which is why I really think Metergoline or another serotonin antagonist would/should be enough - if the correct dosage was used, because it overrides the need for direct depletion or other strategies.

I can just take the sert activators for the rest of my life to keep benefit? I dont mind that.

and the metergoline wouldnt I also need to stay on it forever to keep the benefit ?

Metergoline yes, SERT activators you can cycle for 3-6 months then take a month off etc.

Also another option that might be helpful is checking urine metabolites again as we've spoken. I would really like to know your ranges for MHPG, HVA, Metanephrine/Normetanephrine as well as dynorphin levels. If you can get that lab-work we might be on the road quicker!

Area-1255 wrote:Also another option that might be helpful is checking urine metabolites again as we've spoken. I would really like to know your ranges for MHPG, HVA, Metanephrine/Normetanephrine as well as dynorphin levels. If you can get that lab-work we might be on the road quicker!

what do those mean?

 1 thing I wanted to ask is the serotonin reuptake transporter the same thing as sert? I  know the serotonin reuptake transporter removes serotonin from the synapse .  Is the serotonin transporters everywhere and just moves serotonin quicker ?
btw the sert activators not coming until next week. I have been reading a lot about bacopa and it seems very promising , many say its good for anxiety . . have you used it?

Farshad wrote:

Area-1255 wrote:Also another option that might be helpful is checking urine metabolites again as we've spoken. I would really like to know your ranges for MHPG, HVA, Metanephrine/Normetanephrine as well as dynorphin levels. If you can get that lab-work we might be on the road quicker!

what do those mean?

 1 thing I wanted to ask is the serotonin reuptake transporter the same thing as sert? I  know the serotonin reuptake transporter removes serotonin from the synapse .  Is the serotonin transporters everywhere and just moves serotonin quicker ?
btw the sert activators not coming until next week. I have been reading a lot about bacopa and it seems very promising , many say its good for anxiety . . have you used it?

Serotonin-Transporter is SERT, yes. But when referring to the genes and "Serotonin-Transporter-Linked Polymorphic Region" we then are referring to it as: "5-HTTLPR" the "5-HTT" referring to Serotonin Transporter and "LPR" as in the rest of the term "linked-polymorphic-region".

So SERT and 5-HTT and the "Serotonin Transporter" are the same thing.

cool.. im just waiting for them to arrive I ordered from Iherb.. dont know why its taking so long to come maybe the weather is bad in USA.  I skipped evodiamine  just got the other 3 for now. Which one should I start with? doesent matter? Since I heard so much more about Bacopa  might try it first and a lot of people have written about it and they describe exactly the feeling of reduced serotonin when taking bacopa that I expect would have happend. IE some say more focused .. more relaxed.. so I might start with it first.  I got the Himalaya bacopa, thorne berberine and paradise forskolin.
by increasing sert you get less serotonin receptor activity and from what I read there are serotonin receptors in the amygdala so if increasing sert decreases serotonin receptor expression maybe it can reduce the amygdala activity and such ( all speculations )

Farshad wrote:cool.. im just waiting for them to arrive I ordered from Iherb.. dont know why its taking so long to come maybe the weather is bad in USA.  I skipped evodiamine  just got the other 3 for now. Which one should I start with? doesent matter? Since I heard so much more about Bacopa  might try it first and a lot of people have written about it and they describe exactly the feeling of reduced serotonin when taking bacopa that I expect would have happend. IE some say more focused .. more relaxed.. so I might start with it first.  I got the Himalaya bacopa, thorne berberine and paradise forskolin.
by increasing sert you get less serotonin receptor activity and from what I read there are serotonin receptors in the amygdala so if increasing sert decreases serotonin receptor expression maybe it can reduce the amygdala activity and such ( all speculations   )

Yes, and the amygdala being a key processing center for emotions; Anxiety and Empathy mostly! Some studies show too much amygdala activity can lead to personality disorders as well!

--> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4785144/
--> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3621316/
-->https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3372630/

also my serotonin receptors could be sensetive I had that genetic SNP for it.
So when serotonin  gets to my synapse   and activates the serotonin receptors it will always have a big impact and thus increase amygdala activity a lot more than for someone else + I have fewer SERT expression but SERT could be fixed assuming these supplements work? . The SNP also said my serotonin receptor dont get desensitized so serotonin will always have a bigger effect on me ... So I would have to take like Zyprexa + Bacopa or some other serotonin receptors antagonist.

Farshad wrote:also my serotonin receptors could be sensetive I had that genetic SNP for it.
So when serotonin  gets to my synapse   and activates the serotonin receptors it will always have a big impact and thus increase amygdala activity even more + I have fewer SERT expression but SERT could be fixed assuming these supplements work? . The SNP also said my serotonin receptor dont get desensitized so serotonin will always have a bigger effect on me ... So I would have to take like Zyprexa + Bacopa or something .

I'm not sure if that would be the right idea, Zyprexa has bad effects on weight gain so you may end up feeling unwell and the effects are somewhat unpredictable between the two because Zyprexa (Olanzapine) has mixed effects on serotonergic activity!

I see you've posted on RPF - hopefully they can offer you some Insight, Farshad.
https://raypeatforum.com/community/threads/increasing-sert-serotonin-transporter.21790/

Area-1255 wrote:I see you've posted on RPF - hopefully they can offer you some Insight, Farshad.
https://raypeatforum.com/community/threads/increasing-sert-serotonin-transporter.21790/

insight about what? We have been pretty much over everything when it comes to this serotonin stuff right?. I will try the SERT activators if they dont work  Iwill try Low dosage Prozac. Someone mentioned SSRI after 6 weeks actually start to increase SERT above average . Now im just trying to learn as much as possible about serotonin and how it works in the brain  thats why  I ask so many questions. Reason I posted on there was just curious if anyone had tried any of the herbs listed maybe the could share their experience. Ithink many people on raypeat wanna reduce serotonin so I thought maybe it was a good place to make a thread.

I was wondering do I have the same amount of transporters as a normal person but just my genetic make them inactive or DO I not have enough serotonin transporters? does that make sense?
So if I take  Bacopa   for my SERT issue, how will that work? Say my transporter is low not inactive just very low.. So how would bacopa fix low? Can these HERB activators increase the total amount of serotonin transpoters you have? Or do they just make them more active? or both? if that makes sense.

also something I was wondering was in a study they removed the SERT gene or whatever you wanna call it  so the mice had no SERT they used something like -/- in the text to imply the mice had no SERT. so my question is Wouldnt the mice die if they had no Serotonin transporter as soon as they eat tryptophan food ? wouldnt it lead to serotonin syndrome or what not? maybe I misinterpreted the study wrong idk.

Farshad wrote:I was wondering do I have the same amount of transporters as a normal person but just my genetic make them inactive or DO I not have enough serotonin transporters? does that make sense?
So if I take  Bacopa for my SERT issue, how will that work? Say my transporter is low not inactive just very low.. So how would bacopa fix low? Can these HERB activators increase the total amount of serotonin transpoters you have? Or do they just make them more active? or both? if that makes sense.

The genes contribute to making YOUR transporters LESS active, not "inactive". There's no such thing as a totally inactive transporter.
So the herbs would increase the mRNA and the activities of the transporters. By using multiple, you are also ensuring multiple modes of action.

For example, Evodiamine and Forskolin also activate calmodulin-related pathways that may decrease endogenous (naturally produced) 5-HT/serotonin release.

Additionally, Bacopa increases Acetylcholine which can reduce serotonin release. So you get the benefit from MULTIPLE DIRECTIONS.

Farshad wrote:also something I was wondering was in a study they removed the SERT gene or whatever you wanna call it  so the mice had no SERT they used something like -/- in the text to imply the mice had no SERT. so my question is Wouldnt the mice die if they had no Serotonin transporter as soon as they eat tryptophan food ? wouldnt it lead to serotonin syndrome or what not? maybe I misinterpreted the study wrong idk.

No, the mice wouldn't necessarily die. Everything in science has a different "threshold" - so they might take in a little Tryptophan through the diet and experience unpleasant effects...but those effects would be directly preceding downregulation and desensitization of receptors.

They would be more prone to serotonin syndrome, though.

In that, they would almost certainly experience a lower lifespan.

Area-1255 wrote:

Farshad wrote:also my serotonin receptors could be sensetive I had that genetic SNP for it.
So when serotonin  gets to my synapse   and activates the serotonin receptors it will always have a big impact and thus increase amygdala activity even more + I have fewer SERT expression but SERT could be fixed assuming these supplements work? . The SNP also said my serotonin receptor dont get desensitized so serotonin will always have a bigger effect on me ... So I would have to take like Zyprexa + Bacopa or something .

I'm not sure if that would be the right idea, Zyprexa has bad effects on weight gain so you may end up feeling unwell and the effects are somewhat unpredictable between the two because Zyprexa (Olanzapine) has mixed effects on serotonergic activity!

Are all Serotonin receptors involved in anxiety or just a few which ones if so? I think 5ht2c and 5ht7 are involved in anxiety?

Which drug that is avalibale for prescription should I use instead of zyprexa ? One that doesent also Block SERT.

Mirtazapine  + SERT activators ?

Besides that there are like only Antipsychotic that block Serotonin receptors.

Zyprexa I have tried before but I think it as a low dosage and it was just a one time thing I got because I was at a hospital but it worked great..

https://en.wikipedia.org/wiki/Risperidone

Should I go for Risperidone instead of zyprexa?
5-HT1A 423 Antagonist
5-HT1B 14.9 Antagonist
5-HT1D 84.6 Antagonist
5-HT2A 0.17 Inverse agonist
5-HT2B 61.9 Inverse agonist
5-HT2C 12.0 Inverse agonist
5-HT5A 206 Antagonist
5-HT6 2,060 Antagonist
5-HT7 6.60 Irreversible antagonist

Seems to be missing 5ht3 , 5ht4  and 5ht5b uninmportant in anxiety?

zyprexa blocks those and 5ht3 too but not 5ht4.
https://en.wikipedia.org/wiki/Olanzapine

Farshad wrote:
Besides that there are like only Antipsychotic that block Serotonin receptors.

Zyprexa I have tried before but I think it as a low dosage and it was just a one time thing I got because I was at a hospital but it worked great..

https://en.wikipedia.org/wiki/Risperidone

Should I go for Risperidone instead of zyprexa?
5-HT1A 423 Antagonist
5-HT1B 14.9 Antagonist
5-HT1D 84.6 Antagonist
5-HT2A 0.17 Inverse agonist
5-HT2B 61.9 Inverse agonist
5-HT2C 12.0 Inverse agonist
5-HT5A 206 Antagonist
5-HT6 2,060 Antagonist
5-HT7 6.60 Irreversible antagonist

Seems to be missing 5ht3 , 5ht4  and 5ht5b uninmportant in anxiety?

zyprexa blocks those and 5ht3 too but not 5ht4.
https://en.wikipedia.org/wiki/Olanzapine

Humans don't have 5-HT5B receptors, only 5-HT5A [!].
If Zyprexa worked for you, try it again, but only low dose. I'd expect some weight gain though!

Risperdal (Risperidone) and its benefits on Mood are related to 5-HT7 and 5-HT2C antagonism, but more so the 5-HT1B antagonism.