Progesterone, Testosterone, Allopregnanolone Are Serotonin Antagonists

[Astolfo]

@Sativa Hey. Maybe it's off-topic, but may i ask you about one of my problems?

It's been nearly 1.5 years. At first, I was only getting bowel reactions at exams. As time progressed, this substantially worsened. Now, I can't even go to school, or meet with my friend. I have a hyperreactive bowel that reacts to mental stress. I tried going to doctors but any of them didn't help. It's not a bacterial problem nor related to my diet.
It worsens at nights, sometimes I even wake up earlier because the movement, vibration and noise disturbs me.
Also it worsens when I'm hungry.

I have literally zero anxiety or stress right now. PSSD took all of my cognitive abilities with along my psychological problems.

The only time I remember my bowel has less problems is when I tried 5 mg of vortioxetine.

My current thought is fluoxetine somehow caused my 5-ht2c receptors to be excessively edited(5ht2c-INI, VNV, VSV) (a-to-i). Thus it put me in a prader-willy syndrome like symptoms. (I also have hyperphagia).

You can check my previous posts if you need a lot more information. Or just ask, I can give any information you may need.

Thanks.

 

[S-VV]

This is an interesting conclusion from analyzing lots of research data...
No matter what you do to the 5-HT2C receptor, whether agonize, antagonize, or inverse agonize, you will downregulate it in the long term.

"...many varied effects of the serotonin receptors [5-HT2A is the higher-brain psychedelic receptor, while 5-HT2C is just the flu receptor that makes you feel sick... completely unrelated but classified together because of sequence homology]​

"Kudzu does this by antagonizing the 5-HT2C receptor.
This is basically the "sickness" receptor, when it turns on it inhibits the release of dopamine and norepinephrine, making you feel down, and lethargic.
Blocking it makes you energetic and euphoric. Apparently most people have at least a medium amount of 5-HT2C activation"​

"Hey, guys, 5-HT2C is a crappy receptor to activate.
If daidzin antagonizes this receptor then it should be amazing to take.
5-HT2C isn't a psychedelic receptor, it's the illness receptor.
It turns on when you feel sick. It causes dopamine and norepinephrine release to slow down, reducing dopamine and norepinephrine levels in the body."​

aside: I found the above data using this google search query:
site:tapatalk.com/groups/herbsmxf/ HT2C
Ok, enough quotes from forums, here's some research paper insights:

Constitutively active 5-HT2C receptors reveal novel inverse agonist activity of receptor ligands.
http://www.ncbi.nlm.nih.gov/pubmed/7909313

Chronic mianserin or eltoprazine treatment in rats: effects on the elevated plus-maze test and on limbic 5-HT2C receptor levels.
http://www.ncbi.nlm.nih.gov/pubmed/7813563

Sertindole is a serotonin 5-HT2C inverse agonist and decreases agonist but not antagonist binding to 5-HT2C receptors after chronic treatment.
http://www.ncbi.nlm.nih.gov/pubmed/11594443

SB-243213; a selective 5-HT2C receptor inverse agonist with improved anxiolytic profile: lack of tolerance and withdrawal anxiety.
SB-243213; a selective 5-HT2C receptor inverse agonist with improved anxiolytic profile: lack of tolerance and withdrawal anxiety. - PubMed - NCBI

Novel Actions of Inverse Agonists on 5-HT2C Receptor Systems
Novel Actions of Inverse Agonists on 5-HT2C Receptor Systems​

Great insight, much appreciated.

 

[Sativa]

Do you realize this kind of activation blocks the action of the active site? So it is long-term antagonist without the signal of being continuously active (overactivation-> downregulation like LSD does). I suspect the nausea people describe when coming up on psychedelics is the overactivation phase, and the psychedelic effect comes on as the compensatory downregulation kicks in.

AHA thanks for this clarification.
I basically got that study & misinformed interpretation from an old forum i used to frequent. I'm not formally trained as a pharmacologist so missed that nuance re DA causing 5-HT receptor internalization.
So anything that promotes DA release or increases DA levels, also has an associated 'serotonin antagonism' effect. I'm sure Haidut has mentioned this, re DA levels UP, serotonin receptor activation levels DOWN

 

[Rafael Lao Wai]

hmm, maybe of interest to any of you lot...
@LeeLemonoil @Rafael Lao Wai @Lokzo

Thanks for the tag. Very interesting for sure.

 

[Mauritio]

AHA thanks for this clarification.
I basically got that study & misinformed interpretation from an old forum i used to frequent. I'm not formally trained as a pharmacologist so missed that nuance re DA causing 5-HT receptor internalization.
So anything that promotes DA release or increases DA levels, also has an associated 'serotonin antagonism' effect. I'm sure Haidut has mentioned this, re DA levels UP, serotonin receptor activation levels DOWN

So it means dopamine actually causes lower 5ht2a activation? That would mean drugs like cabergoline or bromocriptine dont have a 5ht2a effect eventhough they "officially" agonize this receptor . That would make them more appealing ,especially given the results that they almost always lead to weight loss and balance most of your hormones back to homeostasis .

Im still not sure what's up with lsd . It is a 5ht2a agonist but it's also a dopamin agonist .
So you might get an overall anti serotonin effect with possible benefits of 5ht2a activation (thinking out of the box) without 5ht2a side effects (depression) ?
It seems so , I have read a lot of case reports on the microdosing subreddit and if it does anything to depression ,it actually helps people.

But I can attest to that 5ht2a activation gives you this broader view ,seeing things in a bigger context , so something's positive about 5ht2a activation, dont know if it's just the BNDF activation...

All of this happens ,given that people take low dosages . Peat advised 10-20mcg of lsd. I actually used to consume 4 mcgs ,that was my sweet spot .

Peat also said it's a strong anti serotonin chemical and that hallucination is actually an effect of serotonin, that's why you dont hallucinate on low doses and get the pro metabolic effects ,because it's not serotonin territory.

I think the whole "serotonin receptor subtype stuff plus interaction with dopamin and other neurotransmitters "is more nuanced than even we at rp forum think . Theres still a lot to learn .