Thoughts on 5HT1A antagonists?

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cdraham
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Re: Thoughts on 5HT1A antagonists?

Unread post by cdraham »

Tree wrote: Fri Feb 12, 2021 7:36 pm
cdraham wrote: Fri Feb 12, 2021 5:33 am
Tree wrote: Fri Feb 12, 2021 1:37 am 5ht1a antagonists will probably not sensitize the receptor because there is a large concentration of serotonin in our synapses from sert down regulation. Antagonists will just increase 5ht firing, by blocking 5ht1a receptors, which will worsen symptoms. We need to focus on finding ways to upregulate sert. All of the negative effects we experience are caused from down stream effects of permeant sert dysfunction induced by ssri. This seems to me like the most plausible explanation for why people have reported crashing from 5ht1a agonists. Most 5ht1a agonist medications/supplements not only target the 5ht1a receptor but they also increase serotonin. If sert is down regulated in pssd, and you take a 5ht1a agonist, serotonin will build up in your system until you crash (more 5ht1a desensitization).
I dont think high Serotonin is a problem in all? I tried some stuff that depletes it and it didnt help one bit
What did you try? If dr sert is the main culprit of pssd, I doubt you would be able to reduce serotonin enough to off set elevated serotonin induced by reduced sert, a critical regulatory mechanism in the brain. I also think it's more than just reducing serotonin. It needs to be reduced in particular parts of the brain and there maybe no practical way to accomplish this without upregulating sert.
Well there are some ways to upregulate SERT; as I know some even tried that, but it didnt work
Tree
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Re: Thoughts on 5HT1A antagonists?

Unread post by Tree »

cdraham wrote: Fri Feb 12, 2021 7:41 pm
Tree wrote: Fri Feb 12, 2021 7:36 pm
cdraham wrote: Fri Feb 12, 2021 5:33 am

I dont think high Serotonin is a problem in all? I tried some stuff that depletes it and it didnt help one bit
What did you try? If dr sert is the main culprit of pssd, I doubt you would be able to reduce serotonin enough to off set elevated serotonin induced by reduced sert, a critical regulatory mechanism in the brain. I also think it's more than just reducing serotonin. It needs to be reduced in particular parts of the brain and there maybe no practical way to accomplish this without upregulating sert.
Well there are some ways to upregulate SERT; as I know some even tried that, but it didnt work
What have you tried? How long? Has anything you've tried made you better or worse? What degree of pssd do you have? Mild, moderate, severe? My experiences and research I've done makes strongly believe that pssd is a sert/5ht1a issue.
cdraham
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Re: Thoughts on 5HT1A antagonists?

Unread post by cdraham »

Tree wrote: Fri Feb 12, 2021 7:53 pm
cdraham wrote: Fri Feb 12, 2021 7:41 pm
Tree wrote: Fri Feb 12, 2021 7:36 pm

What did you try? If dr sert is the main culprit of pssd, I doubt you would be able to reduce serotonin enough to off set elevated serotonin induced by reduced sert, a critical regulatory mechanism in the brain. I also think it's more than just reducing serotonin. It needs to be reduced in particular parts of the brain and there maybe no practical way to accomplish this without upregulating sert.
Well there are some ways to upregulate SERT; as I know some even tried that, but it didnt work
What have you tried? How long? Has anything you've tried made you better or worse? What degree of pssd do you have? Mild, moderate, severe? My experiences and research I've done makes strongly believe that pssd is a sert/5ht1a issue.
Severe, I tried syrian rue microdosing, etc.. but I dont think every symptom can be explained by SERT loss. How do you explain genital shrinkage, etc? I know serotonin receptors have many functions, did you ever research into dynorphin/KOR?
Tree
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Re: Thoughts on 5HT1A antagonists?

Unread post by Tree »

cdraham wrote: Fri Feb 12, 2021 7:55 pm
Tree wrote: Fri Feb 12, 2021 7:53 pm
cdraham wrote: Fri Feb 12, 2021 7:41 pm

Well there are some ways to upregulate SERT; as I know some even tried that, but it didnt work
What have you tried? How long? Has anything you've tried made you better or worse? What degree of pssd do you have? Mild, moderate, severe? My experiences and research I've done makes strongly believe that pssd is a sert/5ht1a issue.
Severe, I tried syrian rue microdosing, etc.. but I dont think every symptom can be explained by SERT loss. How do you explain genital shrinkage, etc? I know serotonin receptors have many functions, did you ever research into dynorphin/KOR?
Is sr the only thing you've tried? sr is a potent MAO-A inhibitor. Chronic use will desensitize 5ht1a receptors even more. I think most symptoms can be explained by sert loss. Before I crashed from ginger, I had mild sexual and severe cognitive symptoms like blunted emotions, fatigue, brain fog induced by ssri. After crash my sexual and cognitive are severe and worse than before crash. I'm certain sert is not functioning properly because I wouldn't have crashed from ginger if I had not taken ssri for three years. Sert loss is why 5ht1a are desensitized and the down stream effects are responsible for most pssd symptoms. After ginger crash, my entire dick went and stayed numb over night. Erections are not as strong and blood doesn't fully reach the tip so it's smaller than what it was before.
cdraham
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Re: Thoughts on 5HT1A antagonists?

Unread post by cdraham »

Tree wrote: Sat Feb 13, 2021 8:00 pm
cdraham wrote: Fri Feb 12, 2021 7:55 pm
Tree wrote: Fri Feb 12, 2021 7:53 pm

What have you tried? How long? Has anything you've tried made you better or worse? What degree of pssd do you have? Mild, moderate, severe? My experiences and research I've done makes strongly believe that pssd is a sert/5ht1a issue.
Severe, I tried syrian rue microdosing, etc.. but I dont think every symptom can be explained by SERT loss. How do you explain genital shrinkage, etc? I know serotonin receptors have many functions, did you ever research into dynorphin/KOR?
Is sr the only thing you've tried? sr is a potent MAO-A inhibitor. Chronic use will desensitize 5ht1a receptors even more. I think most symptoms can be explained by sert loss. Before I crashed from ginger, I had mild sexual and severe cognitive symptoms like blunted emotions, fatigue, brain fog induced by ssri. After crash my sexual and cognitive are severe and worse than before crash. I'm certain sert is not functioning properly because I wouldn't have crashed from ginger if I had not taken ssri for three years. Sert loss is why 5ht1a are desensitized and the down stream effects are responsible for most pssd symptoms. After ginger crash, my entire dick went and stayed numb over night. Erections are not as strong and blood doesn't fully reach the tip so it's smaller than what it was before.
Yeah, syrian rue gave me more numbness too, it made me wake at night with more numbness etc. Its not sustainable.

I found some other stuff that could upregulate sert but i dont know if it would work. The evidence is weak

Do you also experience a loss of deep sleep?
heymartinn
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Re: Thoughts on 5HT1A antagonists?

Unread post by heymartinn »

Tree wrote: Sat Feb 13, 2021 8:00 pm
Is sr the only thing you've tried? sr is a potent MAO-A inhibitor. Chronic use will desensitize 5ht1a receptors even more. I think most symptoms can be explained by sert loss. Before I crashed from ginger, I had mild sexual and severe cognitive symptoms like blunted emotions, fatigue, brain fog induced by ssri. After crash my sexual and cognitive are severe and worse than before crash. I'm certain sert is not functioning properly because I wouldn't have crashed from ginger if I had not taken ssri for three years. Sert loss is why 5ht1a are desensitized and the down stream effects are responsible for most pssd symptoms. After ginger crash, my entire dick went and stayed numb over night. Erections are not as strong and blood doesn't fully reach the tip so it's smaller than what it was before.

Although my knowledge is really limited regarding neurochemistry, I think my personal experience backs up your claim. Before any crash I've had only sexual issues: numb genitals, delayed ejaculation, muted orgasm etc. No emotional blunting or anhedonia, could get somewhat horny and aroused. 6 months pass after cessation of the SNRI, I've went to a party and throughout the night I've took around 300mg of MDMA. The drug effects were completely diminished, as with psychedelics which I've tried in the past, probably due to persistent 5ht2a desensitization due to meds. The main part is, that the next day I woke up with severe anhedonia, emotional blunting, premature ejaculation, my sexual symptoms and cognitive abilities has worsened too. Another 6 months pass and my condition haven't changed much, so I've decided to trial Perika's hyperforin SJW. I've took it for 1 month and my initial anhedonia, brain fog and sexual functioning just plummeted to even greater depths. These effects seems to be long lasting. One of hyperforin actions is also to inhibit serotonin reuptake. So as you said earlier: everytime serotonin levels rise in the brain - the result is more desensitized 5hta1 cause there's not enough SERT for a proper reuptake to happen.
cdraham
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Re: Thoughts on 5HT1A antagonists?

Unread post by cdraham »

heymartinn wrote: Sun Feb 14, 2021 8:55 am
Tree wrote: Sat Feb 13, 2021 8:00 pm
Is sr the only thing you've tried? sr is a potent MAO-A inhibitor. Chronic use will desensitize 5ht1a receptors even more. I think most symptoms can be explained by sert loss. Before I crashed from ginger, I had mild sexual and severe cognitive symptoms like blunted emotions, fatigue, brain fog induced by ssri. After crash my sexual and cognitive are severe and worse than before crash. I'm certain sert is not functioning properly because I wouldn't have crashed from ginger if I had not taken ssri for three years. Sert loss is why 5ht1a are desensitized and the down stream effects are responsible for most pssd symptoms. After ginger crash, my entire dick went and stayed numb over night. Erections are not as strong and blood doesn't fully reach the tip so it's smaller than what it was before.

Although my knowledge is really limited regarding neurochemistry, I think my personal experience backs up your claim. Before any crash I've had only sexual issues: numb genitals, delayed ejaculation, muted orgasm etc. No emotional blunting or anhedonia, could get somewhat horny and aroused. 6 months pass after cessation of the SNRI, I've went to a party and throughout the night I've took around 300mg of MDMA. The drug effects were completely diminished, as with psychedelics which I've tried in the past, probably due to persistent 5ht2a desensitization due to meds. The main part is, that the next day I woke up with severe anhedonia, emotional blunting, premature ejaculation, my sexual symptoms and cognitive abilities has worsened too. Another 6 months pass and my condition haven't changed much, so I've decided to trial Perika's hyperforin SJW. I've took it for 1 month and my initial anhedonia, brain fog and sexual functioning just plummeted to even greater depths. These effects seems to be long lasting. One of hyperforin actions is also to inhibit serotonin reuptake. So as you said earlier: everytime serotonin levels rise in the brain - the result is more desensitized 5hta1 cause there's not enough SERT for a proper reuptake to happen.
How is your sleep quality?
Calm Amygdala
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Re: Thoughts on 5HT1A antagonists?

Unread post by Calm Amygdala »

Tree wrote: Fri Feb 12, 2021 1:37 am 5ht1a antagonists will probably not sensitize the receptor because there is a large concentration of serotonin in our synapses from sert down regulation. Antagonists will just increase 5ht firing, by blocking 5ht1a receptors, which will worsen symptoms. We need to focus on finding ways to upregulate sert. All of the negative effects we experience are caused from down stream effects of permeant sert dysfunction induced by ssri. This seems to me like the most plausible explanation for why people have reported crashing from 5ht1a agonists. Most 5ht1a agonist medications/supplements not only target the 5ht1a receptor but they also increase serotonin. If sert is down regulated in pssd, and you take a 5ht1a agonist, serotonin will build up in your system until you crash (more 5ht1a desensitization).
I thought that 5ht1a agonists tend to decrease serotoinin, as 5ht1a is an autoreceptor.
Tree
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Re: Thoughts on 5HT1A antagonists?

Unread post by Tree »

Calm Amygdala wrote: Mon May 03, 2021 4:55 pm
Tree wrote: Fri Feb 12, 2021 1:37 am 5ht1a antagonists will probably not sensitize the receptor because there is a large concentration of serotonin in our synapses from sert down regulation. Antagonists will just increase 5ht firing, by blocking 5ht1a receptors, which will worsen symptoms. We need to focus on finding ways to upregulate sert. All of the negative effects we experience are caused from down stream effects of permeant sert dysfunction induced by ssri. This seems to me like the most plausible explanation for why people have reported crashing from 5ht1a agonists. Most 5ht1a agonist medications/supplements not only target the 5ht1a receptor but they also increase serotonin. If sert is down regulated in pssd, and you take a 5ht1a agonist, serotonin will build up in your system until you crash (more 5ht1a desensitization).
I thought that 5ht1a agonists tend to decrease serotoinin, as 5ht1a is an autoreceptor.
Presynaptic and postsynaptic 5ht1a receptors inhibit serotonin release. Agonists don't decrease serotonin. Most drugs/supplements that are 5ht1a agonists also increase serotonin.
Gonzo
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Re: Thoughts on 5HT1A antagonists?

Unread post by Gonzo »

Tree wrote: Tue May 04, 2021 2:15 am
Calm Amygdala wrote: Mon May 03, 2021 4:55 pm
Tree wrote: Fri Feb 12, 2021 1:37 am 5ht1a antagonists will probably not sensitize the receptor because there is a large concentration of serotonin in our synapses from sert down regulation. Antagonists will just increase 5ht firing, by blocking 5ht1a receptors, which will worsen symptoms. We need to focus on finding ways to upregulate sert. All of the negative effects we experience are caused from down stream effects of permeant sert dysfunction induced by ssri. This seems to me like the most plausible explanation for why people have reported crashing from 5ht1a agonists. Most 5ht1a agonist medications/supplements not only target the 5ht1a receptor but they also increase serotonin. If sert is down regulated in pssd, and you take a 5ht1a agonist, serotonin will build up in your system until you crash (more 5ht1a desensitization).
I thought that 5ht1a agonists tend to decrease serotoinin, as 5ht1a is an autoreceptor.
Presynaptic and postsynaptic 5ht1a receptors inhibit serotonin release. Agonists don't decrease serotonin. Most drugs/supplements that are 5ht1a agonists also increase serotonin.
So serotonin agonists may be dangerous?
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