NEED TO FIX 5-HT2C RECEPTOR

[Cipro]

Hello to all. I'm astolfo from rpforum and ciprofloxacin from pssdforum in case of anyone recognizes.

I have a serious progressive disease. Metabolic syndrome, bowel reactivity, myoclonus, agitation, muscle control problems, disassociation, cognitive decline, loss of emotion, visual, smell perception, excessive daytime sleepiness, very mild alergic symptoms to some foods, unrefreshing sleepines and disturbed sleep cycle, excessive hungriness(I'm normally a very skinny guy but I'm becoming obese), metabolic syndrome etc.

My problems seems like autoimmunity + high serotonin + adrenal insufficiency + loss of 5-HT2C + Kynurenine imbalance bla bla bla

That was the TL;DR of my 2 years of adventure. Actually I'm near of the suicide because my life completely ruined, long story.


I suspect I just downregulated my 2C receptors too much that it caused loss of hpa-axis activation. And that further caused adrenal insufficiency, and all other symtpoms as a consequences.


TL;DR:

HOW CAN I UPREGULATE 2CRs AND FIX THE HPA-AXIS?


Several posts you may read to know more about my symptoms (articles are included):

High Serotonin, Low 5-HT2C, Adrenal Insufficiency, HELP?

I need to upregulate 5-HT2C. Antagonists doesn't work, is there any way to upregulate these receptors significantly?

raypeatforum.com

The Connection Of Serotonin And Bowel Movements?

Well, some people get that from salicylates and it can affect the blood... If you're not getting clear benefits from aspirin I would stop it. I had eye problems but I don't know what fixed them. Amino acids are a good bet, and also things that help shuttle fatty acids like carnitine (because...

raypeatforum.com

How to upregulate/fix 5-HT2C?

Hey @Helen . Could you find anything?

hackstasis.com

 

[falsifiedhypothesi]

Have you talked to a doctor about this? I'm not trying to downplay your suffering as it sounds like your day to day is pretty rough but if you're self diagnosing you could be looking for the answers to the wrong questions.

 

[Cipro]

Have you talked to a doctor about this? I'm not trying to downplay your suffering as it sounds like your day to day is pretty rough but if you're self diagnosing you could be looking for the answers to the wrong questions.

I went to several doctors. They didn't take it serious. They don't even aware of that psychiatric drugs can cause permanent side effects.

 

[Blowmonkey]

Try a neurologist instead. Why don't you follow helen's advice and seek out 5ht2c agonists to try btw? If that's what you suspect is wrong with you, taking one might alleviate you of a lot of those problems. I hope it's that simple for your sake, but I suspect it's not just attributable to just that one receptor.

 

[Cipro]

Try a neurologist instead. Why don't you follow helen's advice and seek out 5ht2c agonists to try btw? If that's what you suspect is wrong with you, taking one might alleviate you of a lot of those problems. I hope it's that simple for your sake, but I suspect it's not just attributable to just that one receptor.

I tried to seek some help from neurologists too. They don't take uncommunicable diseases seriously.

Helen suggested lorcaserine and posted the link of wikipedia page. But there is no publicly available 2C agonist right now. Lorcaserine is not available at my country.

You're right, it's not that simple but whatever keeps me in this loophole could be as simple as one receptor. If you read the last post on this topic, there are some studies regarding 5-HT2CRs effect on GR receptors on the brain. 5-HT2C is such a complex receptor itself, because it affects the HPA-Axis.

@Blowmonkey Also, if that counts as a clue, but I feel better (especially my bowel reactivity problems) after getting an ilness.

There are two possibilities:

1 - It helped me because getting ilness improves my symptoms by increasing IDO activity(More kynurenine synthesized from tryptophan, less is available for serotonin):

https://www.omf.ngo/wp-content/uploads/2018/11/Edited-Robert-Phair-Metabolic-Trap.pdf

Dr. Ron Davis: Yep and what we, so what we really want to do is to activate IDO1, not suppress it, and we don't know how really to do that. Yeah so if there's anybody out there that wants to set up a pharmaceutical company that would be a good target. But you can see it happening in other
situations. So when you get a infection, not all infections, but many infections activate IDO1 and that is consistent with some of the patients saying, and we seen in our own son, you get better after an infection. In fact there are some cases that have been reported, that people actually get cured by an infection. They say I’m over it and you ask how'd you get over it, I had an infection and all the sudden I got better. Now don't go out there and eat dirt and try to find some microbe right, hoping to get a bad infection because it could kill you and it's not guaranteed to activate IDO1. But you know there are some things here that have substance that we can figure, we can explain, can explore.

2 - It helped my because cytokines 'upregulate' 5-HT2C receptors:

5-HT2C Receptors: What Are They, And What Do They Do? - SelfHacked

5-HT2C receptors are a key part of the brain’s serotonin system. But what exactly do we know about their role in the brain? Read on to learn more!

selfhacked.com

The 5-HT2C receptor is increased by inflammatory cytokines.

 

[Blowmonkey]

Man, this is all terribly advanced, I think you're better off in the forum neuroscience and pharmacology instead of bdd. I wish I could help you further, but I can't atm, I'd need to delve deeper, I really don't have the energy to do so. It's been years since I actively read about neuroscience, it fueled my paranoia and hypochondria, you start making connections that are built on laymen hypotheses, not advantageous to your or anyone's health. Maybe there's some of that going on here too, but I believe you're not wrong in thinking it was the medication that caused a lot of these problems.

Shame you can't find any, didn't know it was that hard to acquire. Nowadays usually anything can be found on the internet though, if it can't be done legally, just order some yourself, whatever.

 

[Keif' Richards]

Moving to neuroscience as this doesn't necessarily fit in with our milleux here in BDD. I hope you can get some help over there!

 

[d1nach]

Im pretty sure 5ht2c receptors downregulate from both agonism and antagonism.

 

[Rectify]

Do *NOT* try clonazolam.

 

[sekio]

Why are you concerned about 5-HT2c specifically? What evidence do you have that it's one, very specific, receptor causing your problems? (I somehow doubt you have a history of regular PET scans with radiolabeled 5-HT2c ligands to compare "before and after")...

What about the other ~dozen 5HT receptors? Why would 2c downregulate on its own if there is excess serotonin?

My advice to people who insist one specific receptor is "dysfunctional" is: you are probably missing the forest for the trees. Even if you are correct in assuming 5HT2cR is messed up, there is no "wonder drug" to make everything better.

 

[Cipro]

Why are you concerned about 5-HT2c specifically? What evidence do you have that it's one, very specific, receptor causing your problems?

What about the other ~dozen 5HT receptors?

My advice to people who insist one specific receptor is "dysfunctional" is: you are probably missing the forest for the trees. Even if you are correct in assuming 5HT2cR is messed up, there is no "wonder drug" to make everything better.

Thanks, but these type of posts don't make any sense.

Of course I know as well as like you do, that we are complex organisms. But if you wonder why I'm obsessing that much on an only one receptor, than just read the topics I posted above. These links are posted in this topic for a reason.

Why would 2c downregulate on its own if there is excess serotonin?

Isn't it how it works? You say, high levels of serotonin causes 2CRs to be upregulate?

That study says opposite. Actually, SERT knockout mice has less functional 2C receptors (because of RNA re-editing)

Altered 5-HT2C receptor agonist-induced responses and 5-HT2C receptor RNA editing in the amygdala of serotonin transporter knockout mice - PubMed

These results indicate that the 5-HT2CR in the amygdala of SERT-/- mice has increased RNA editing, which could explain, at least in part, the decreased behavioral responses to 5-HT2C agonists in SERT-/- mice. These alterations in 5-HT2CR in amygdala may be relevant to humans with SERT...

www.ncbi.nlm.nih.gov

Compared to SERT+/+ mice, SERT-/- mice showed a decrease in less edited, highly functional 5-HT2C isoforms, and an increase in more edited isoforms with reduced signaling efficiency

So, there are three possibilities. Fluoxetine changed the rna structure of these receptors, being in highly serotonergic state changed the rna structure of these receptors, or both. Maybe more than that.

 

[Båtmannen]

High levels of serotoin causes more activation at serotonin receptors, yes. Unless of course there is something wrong with you.

And while it's true that in normal people, even partial agonists (you'll have a hard time getting 5-HT-agonists prescribed) act more like functional antagonists than agonists. If you do lack activity at this receptor, however, a partial agonist, and there is only one that I know of, will occupy and activate the receptor. The partial agonist is Aripiprazole/Abilify, and while it takes alot of it for it to occupy the receptor, the activation once it does, is significant and high.

But there's no taking the 2,5 mg:s recommended for MDD and hoping it will even touch the 5-HT2c-receptor, and with increased dosage, increased risk for side effects. However, abilify is perhaps the least unhealthy antipsychotic (even increases gray matter in the brain), and the side effects are nothing like the awful **** you'd get on high doses of Haldod, Risperidone or even Olanzapine (sedation and insatiable hunger and f'ed up metabolism). It's even cardio-protective! (Most likely)

Thanks, but these type of posts don't make any sense.

Of course I know as well as like you do, that we are complex organisms. But if you wonder why I'm obsessing that much on an only one receptor, than just read the topics I posted above. These links are posted in this topic for a reason.



Isn't it how it works? You say, high levels of serotonin causes 2CRs to be upregulate?

That study says opposite. Actually, SERT knockout mice has less functional 2C receptors (because of RNA re-editing)

Altered 5-HT2C receptor agonist-induced responses and 5-HT2C receptor RNA editing in the amygdala of serotonin transporter knockout mice - PubMed

These results indicate that the 5-HT2CR in the amygdala of SERT-/- mice has increased RNA editing, which could explain, at least in part, the decreased behavioral responses to 5-HT2C agonists in SERT-/- mice. These alterations in 5-HT2CR in amygdala may be relevant to humans with SERT...

www.ncbi.nlm.nih.gov

So, there are three possibilities. Fluoxetine changed the rna structure of these receptors, being in highly serotonergic state changed the rna structure of these receptors, or both. Maybe more than that.

But wasn't it different between the two rat groups? My english lacks too much to understand it fully.

However, if you have high levels of serotonin, you will most likely also have it where the receptors are located (remember like 75 % of 5-HT receptors are located in your bowels). Why would a receptor react by downregulate, if there in an increase in a substance who binds to the receptor?


But perhaps serotonin has shit to do with depression/anxiety, unless you really flood the brain (with recreational drugs). If the reason for depression was low levels of 5-HT, DA and NE, and thereby low activity at the receptors - depression would no longer be a problem. Like, take a large dose of Venlafaxine today, and you'll have the biochemical effects in hours. Yet it takes a month for it to start working.

 

[Cipro]

High levels of serotoin causes more activation at serotonin receptors, yes. Unless of course there is something wrong with you.

And while it's true that in normal people, even partial agonists (you'll have a hard time getting 5-HT-agonists prescribed) act more like functional antagonists than agonists. If you do lack activity at this receptor, however, a partial agonist, and there is only one that I know of, will occupy and activate the receptor. The partial agonist is Aripiprazole/Abilify, and while it takes alot of it for it to occupy the receptor, the activation once it does, is significant and high.

But there's no taking the 2,5 mg:s recommended for MDD and hoping it will even touch the 5-HT2c-receptor, and with increased dosage, increased risk for side effects. However, abilify is perhaps the least unhealthy antipsychotic (even increases gray matter in the brain), and the side effects are nothing like the awful **** you'd get on high doses of Haldod, Risperidone or even Olanzapine (sedation and insatiable hunger and f'ed up metabolism). It's even cardio-protective! (Most likely)

Aripiprazol is a strong dopamine receptor antagonist. How do I know if it somehow improves my situation?

Why would a receptor react by downregulate, if there in an increase in a substance who binds to the receptor?

Desensitization? You mean, more receptor; less activity? That maybe explain cognitive deteoriation(low dopamine), but it conflicts because of its anxiogenic properties. I'm autistic, I had an extreme anxiety disorder all my life. That's turned upside down.

Also being easily bloated is a sign of hpa dysfunction. I have bloating only in special conditions (mental task, at nights, when hungry, after protein..).

Neiterh Antibiotics or natural antibiotics (like garlic juice) helped a bit.

Things did help:

- licorice (11ß-HSD2 inhibitor)
- vortioxetine


Things did make worse

- Coffee ( 11ß-HSD1 inhibitor)
- Cyptoheptadine (antagonizes literally everything)

 

[Båtmannen]

Desensitization? You mean, more receptor; less activity? That maybe explain cognitive deteoriation(low dopamine), but it conflicts because of its anxiogenic properties. I'm autistic, I had an extreme anxiety disorder all my life. That's turned upside down.

If desensitization was as prevalent as you suggest, then no antidepressants would work in the long term, right?

Are you saying aripiprazole has anxiogenic properties? It can be used for irritability in people with autism, by the way.

Aripiprazole is not primarily a strong dopamine antagonist; at the presynaptic receptors it is a partial AGONIST. And the higher the dosage, the higher the antagonstic effect.

I just checked Wikipedia and 2 mg is enough to occupy 71 % of D2 receptors, and at 40 mg it's closer to 100 % than 90 %, but

 

[Cipro]

If desensitization was as prevalent as you suggest, then no antidepressants would work in the long term, right?

Why? Less 2C = less anxiety. When downregulation/desensitization occurs, you get less amount of 2C or the same amount but less effective version(rna-reediting).

Fluoxetine actually quite worked on me. I used to be an extremely anxious person but it slowly resolved. "Even", my suicidal urges slowly went away. I have every required material in my hand right now, as it's impossible to live like that - but I have zero psychological urge to do it.

Search on google, "5-ht2c and suicidality"

 

[Båtmannen]

This is how a partial agonist works:

https://qph.fs.quoracdn.net/main-qimg-60d2ed5d3ac8e0b3d3df81b0f586ab96

And you also mentioned you have high levels of serotonin - that makes Abilify a 5-HT2c antagonist.

If i was your doctor, I would never use Abilify as a first-line treatment (obviously) but as an add-on therapy, and I thought this was obvious as you're not psychotic. And the reason for using this and not second-generation anti-psychotics, is that this medication has far less serious side effects and does not zombify you (generally speaking).

What, you have the required material in your hand? To solve your problems? Yet zero urge to do it? Or is it my english antagonizing my ability to understand you?


This combination would be your best option:

Bupropion 300 mg
Vortieoxtine, a low or really low dose, as bupropion will increase the AUC A LOT.
Aripiprazole
Clonazepam or Alprazolam,
Perhaps remove Vortioxetine for Mirtazapine, which works VERY well with Bupropion, and antagonizes 5-HT2C.

You mentioned Vortioxetine works, and Bupropion + Mirtazapine + 5HT1a-activation will make wonders with your depression and 5-HT2c will be fucking put in it's place. And Bupropion/Mirtazapine will have synergistic effects on your adrenal insuffiency. MIirtazapine will increase it, while Bupropion will decrease the reuptake.

You seem depressed as well as full of anxiety.

Wait, what. You want to UPREGULATE/ACTIVATE the receptor causing your problems? Please explain how you are thinking.


Sorry I didn't read everything you had linked or even your first post enough. II hadn't slept for several days yesterday,