Sonny on Wed Dec 08, 2010 12:38 pm
Post one, the short version
This is going to be the short version of what I know. Later I will post replies filling in the details, like how I know these things for example.
PSSD is caused by permanent desensitization of the 5HT1A receptor. This desensitization causes a build up of serotonin at receptors of this type. The post synaptic 5HT1A receptors have little to do with this. It is mainly the presynaptic receptors or autoreceptors that matter. This is because these regulate the post synaptic receptors. However many of the presynaptic receptors do not have any post synaptic serotonin receptors that they regulate. They instead regulate different dopamine receptors and also glutimate. The dopamine receptors are the main ones we are concerned with. The 5HT1A receptors have an inhibitory effect on these dopamine receptors. The dopamine receptors are the ones that control your sexual response....well at least in certain parts of the brain anyway. Certain dopamine receptors must reach a sort of critical mass, which is the cause and some of the effect of orgasm. The build up has much to do with the feeling of sexual activity too. As you may know, Anafronil (a tricyclic) can give you similar sexual side effects to an SSRI. It acts directly on the dopamine receptors as an antagonist, while the SSRIs increase serotonin on the 5HT1A, which in turn inhibits dopamine. If a person with PSSD takes an SSRI again, they should notice the effects occur within days of taking it, which is IMPOSSIBLE in the general population. This is because the receptors are already desensitized and don't have to wait for that process, so the build up happens rapidly. One may also notice that dopamine agonists can help a little but are of limited effectiveness. This is because even if you have additional dopamine, your 5HT1A receptors are still going to downregulate them due to their inhibitory effect.
So theoretically a partial agonist in higher doses should do the trick as this will bind to the receptor blocking the serotonin, but will cause less activation. Therefor the net result will be a less activated set of receptors, in turn exhibiting less inhibitory control on the dopamine receptors. An antagonist is likely to work well too, especially one that exerts a potent blockade of the 5HT1A receptors. An inverse agonist would be worth a shot but could have some nasty, unpredictable sides. However it could be that a low dose may be alright.
Ok so maybe that was more of a medium version.....whatever.
my research - Sonny OP
Re: my research (Sonny)
Sonny on Fri Dec 10, 2010 8:55 am
Back in 2005 before I knew any better, I let psychiatrist talk me into trying Paxil. It turned out to be unpleasant but interesting. By the middle of the third day my genital area was completely unresponsive. Normally it is not possible to get the effects of an SSRI so quickly. This is good evidence of my original time on Prozac in the early 90's permanently desensitizing my 5HT1A receptors.
Another good piece of evidence is that they are using 5HT1A full agonists to quickly increase serotonin and thereby make SSRI take effect with 3 days or so.
Another interesting piece of evidence is when later in 2005, a different psychiatrist I tried had me try Anafronil. It gave me the exact same symptoms as the Paxil. It was just as quick too. The different is it doesn't make the inhibitory effect of the 5HT1A worse, it directly affects the dopamine receptors itself. It acts as a dopamine antagonist. The sameness in symptoms is good evidence of the cause of this issue.
Back in 2005 before I knew any better, I let psychiatrist talk me into trying Paxil. It turned out to be unpleasant but interesting. By the middle of the third day my genital area was completely unresponsive. Normally it is not possible to get the effects of an SSRI so quickly. This is good evidence of my original time on Prozac in the early 90's permanently desensitizing my 5HT1A receptors.
Another good piece of evidence is that they are using 5HT1A full agonists to quickly increase serotonin and thereby make SSRI take effect with 3 days or so.
Another interesting piece of evidence is when later in 2005, a different psychiatrist I tried had me try Anafronil. It gave me the exact same symptoms as the Paxil. It was just as quick too. The different is it doesn't make the inhibitory effect of the 5HT1A worse, it directly affects the dopamine receptors itself. It acts as a dopamine antagonist. The sameness in symptoms is good evidence of the cause of this issue.
Re: my research (Sonny)
Sonny on Tue Dec 14, 2010 8:04 am
I have been conferring with someone else on this issue, who brought this to my attention.
http://www.ncbi.nlm.nih.gov/pubmed/17617388
I looked into this and came up with something new to try.
http://www.thorne.com/Products/Antioxid ... ~SF775.jsp
You can't buy it there though. I got it from Amazon.
I have been conferring with someone else on this issue, who brought this to my attention.
http://www.ncbi.nlm.nih.gov/pubmed/17617388
I looked into this and came up with something new to try.
http://www.thorne.com/Products/Antioxid ... ~SF775.jsp
You can't buy it there though. I got it from Amazon.
Re: my research (Sonny)
Justin on Tue Oct 11, 2011 6:45 am
Hi Sonny, not to contradict you but I'll talk from my own experiences. The first time I took Effexor I had sexual side effects within a day or two. I had never had them before period. It was my first time taking any SSRI.
I did take Ritalin as a kid so maybe that had something to do with my fast response but it could also be possible that some people develop side effects more or less immediately even if they did not take SSRIs previously.
Sonny wrote:
Back in 2005 before I knew any better, I let psychiatrist talk me into trying Paxil. It turned out to be unpleasant but interesting. By the middle of the third day my genital area was completely unresponsive. Normally it is not possible to get the effects of an SSRI so quickly. This is good evidence of my original time on Prozac in the early 90's permanently desensitizing my 5HT1A receptors.
Another good piece of evidence is that they are using 5HT1A full agonists to quickly increase serotonin and thereby make SSRI take effect with 3 days or so.
Another interesting piece of evidence is when later in 2005, a different psychiatrist I tried had me try Anafronil. It gave me the exact same symptoms as the Paxil. It was just as quick too. The different is it doesn't make the inhibitory effect of the 5HT1A worse, it directly affects the dopamine receptors itself. It acts as a dopamine antagonist. The sameness in symptoms is good evidence of the cause of this issue.
Hi Sonny, not to contradict you but I'll talk from my own experiences. The first time I took Effexor I had sexual side effects within a day or two. I had never had them before period. It was my first time taking any SSRI.
I did take Ritalin as a kid so maybe that had something to do with my fast response but it could also be possible that some people develop side effects more or less immediately even if they did not take SSRIs previously.
Sonny wrote:
Back in 2005 before I knew any better, I let psychiatrist talk me into trying Paxil. It turned out to be unpleasant but interesting. By the middle of the third day my genital area was completely unresponsive. Normally it is not possible to get the effects of an SSRI so quickly. This is good evidence of my original time on Prozac in the early 90's permanently desensitizing my 5HT1A receptors.
Another good piece of evidence is that they are using 5HT1A full agonists to quickly increase serotonin and thereby make SSRI take effect with 3 days or so.
Another interesting piece of evidence is when later in 2005, a different psychiatrist I tried had me try Anafronil. It gave me the exact same symptoms as the Paxil. It was just as quick too. The different is it doesn't make the inhibitory effect of the 5HT1A worse, it directly affects the dopamine receptors itself. It acts as a dopamine antagonist. The sameness in symptoms is good evidence of the cause of this issue.
Re: my research (Sonny)
Justin on Tue Oct 11, 2011 6:47 am
Sonny wrote:
I have been conferring with someone else on this issue, who brought this to my attention.
I looked into this and came up with something new to try.
You can't buy it there though. I got it from Amazon.
I am confused. Do we want to increase 5HT(1A) receptors or decrease them. Your different posts seem to be suggesting different things.
Justin
Sonny wrote:
I have been conferring with someone else on this issue, who brought this to my attention.
I looked into this and came up with something new to try.
You can't buy it there though. I got it from Amazon.
I am confused. Do we want to increase 5HT(1A) receptors or decrease them. Your different posts seem to be suggesting different things.
Justin
Re: my research (Sonny)
Sonny on Tue Oct 11, 2011 8:36 am
Justin wrote:
Hi Sonny, not to contradict you but I'll talk from my own experiences. The first time I took Effexor I had sexual side effects within a day or two. I had never had them before period. It was my first time taking any SSRI.
I did take Ritalin as a kid so maybe that had something to do with my fast response but it could also be possible that some people develop side effects more or less immediately even if they did not take SSRIs previously.
Sonny wrote:
Back in 2005 before I knew any better, I let psychiatrist talk me into trying Paxil. It turned out to be unpleasant but interesting. By the middle of the third day my genital area was completely unresponsive. Normally it is not possible to get the effects of an SSRI so quickly. This is good evidence of my original time on Prozac in the early 90's permanently desensitizing my 5HT1A receptors.
Another good piece of evidence is that they are using 5HT1A full agonists to quickly increase serotonin and thereby make SSRI take effect with 3 days or so.
Another interesting piece of evidence is when later in 2005, a different psychiatrist I tried had me try Anafronil. It gave me the exact same symptoms as the Paxil. It was just as quick too. The different is it doesn't make the inhibitory effect of the 5HT1A worse, it directly affects the dopamine receptors itself. It acts as a dopamine antagonist. The sameness in symptoms is good evidence of the cause of this issue.
The side effects started after a day, it was just on the third day it got that bad. However when I took prozac a long time ago, that took quite some time to cause problems. But I am a sample size of one, so it might vary from person to person. Now the primary effects on the other hand, that was two weeks to notice anything, and more like a month for the full affect with the prozac.
Justin wrote:
Hi Sonny, not to contradict you but I'll talk from my own experiences. The first time I took Effexor I had sexual side effects within a day or two. I had never had them before period. It was my first time taking any SSRI.
I did take Ritalin as a kid so maybe that had something to do with my fast response but it could also be possible that some people develop side effects more or less immediately even if they did not take SSRIs previously.
Sonny wrote:
Back in 2005 before I knew any better, I let psychiatrist talk me into trying Paxil. It turned out to be unpleasant but interesting. By the middle of the third day my genital area was completely unresponsive. Normally it is not possible to get the effects of an SSRI so quickly. This is good evidence of my original time on Prozac in the early 90's permanently desensitizing my 5HT1A receptors.
Another good piece of evidence is that they are using 5HT1A full agonists to quickly increase serotonin and thereby make SSRI take effect with 3 days or so.
Another interesting piece of evidence is when later in 2005, a different psychiatrist I tried had me try Anafronil. It gave me the exact same symptoms as the Paxil. It was just as quick too. The different is it doesn't make the inhibitory effect of the 5HT1A worse, it directly affects the dopamine receptors itself. It acts as a dopamine antagonist. The sameness in symptoms is good evidence of the cause of this issue.
The side effects started after a day, it was just on the third day it got that bad. However when I took prozac a long time ago, that took quite some time to cause problems. But I am a sample size of one, so it might vary from person to person. Now the primary effects on the other hand, that was two weeks to notice anything, and more like a month for the full affect with the prozac.
Re: my research (Sonny)
Sonny on Tue Oct 11, 2011 8:49 am
Justin wrote:
Sonny wrote:
I have been conferring with someone else on this issue, who brought this to my attention.
I looked into this and came up with something new to try.
You can't buy it there though. I got it from Amazon.
I am confused. Do we want to increase 5HT(1A) receptors or decrease them. Your different posts seem to be suggesting different things.
Justin
You want to decrease it. There are counter-intuitive ways to do that though. An antagonist is the straightforward way. A partial agnoist will cause a lower net effect because it only partially binds to the receptor. Then another option is to take something that will resensitize the receptor, which should result in less serotonin at the receptor site.
The particular 5HT1A receptors in question are called autoreceptors if I remember right. They have an inhibitory effect on dopamine receptors. That is my best theory as to the root cause. It fits with my observations. Like for example dopamine agonists being effective only up to a certain point. I am guessing the amount of dopamine you can get there is capped by the 5HT1A.
But I'm open to exploring other theories, I'll go where ever the evidence leads.
Justin wrote:
Sonny wrote:
I have been conferring with someone else on this issue, who brought this to my attention.
I looked into this and came up with something new to try.
You can't buy it there though. I got it from Amazon.
I am confused. Do we want to increase 5HT(1A) receptors or decrease them. Your different posts seem to be suggesting different things.
Justin
You want to decrease it. There are counter-intuitive ways to do that though. An antagonist is the straightforward way. A partial agnoist will cause a lower net effect because it only partially binds to the receptor. Then another option is to take something that will resensitize the receptor, which should result in less serotonin at the receptor site.
The particular 5HT1A receptors in question are called autoreceptors if I remember right. They have an inhibitory effect on dopamine receptors. That is my best theory as to the root cause. It fits with my observations. Like for example dopamine agonists being effective only up to a certain point. I am guessing the amount of dopamine you can get there is capped by the 5HT1A.
But I'm open to exploring other theories, I'll go where ever the evidence leads.
Re: my research (Sonny)
Oxytocin
Post Justin on Fri Oct 14, 2011 6:14 am
I thought you might find this interesting given your theory and your condition. Oxytocin is released when we form love relationships. I don't know but perhaps this is related to why many people who seem to recover seem to do so when they allow themselves to date again. We'll see I'd do anything to recover!
Oxytocin involvement in SSRI-induced delayed ejaculation: a review of animal studies.
de Jong TR, Veening JG, Olivier B, Waldinger MD.
Source
Department of Psychopharmacology, Utrecht Institute of Pharmacological Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands.
Abstract
INTRODUCTION:
Selective serotonin reuptake inhibitors (SSRIs) differ in the severity of induced ejaculation delay. Various studies indicate that oxytocin is involved in sexual behavior.
AIM:
To review and evaluate the involvement of oxytocin in SSRI-induced ejaculation delay.
MAIN OUTCOME MEASURES:
Oxytocine release, 5-hydroxytryptamine (5-HT) neurotransmission, and desensitization of 5-HT(1A) receptors.
METHODS:
A review and critical analysis of animal studies investigating the interaction of serotonergic and oxytocinergic neurotransmission in relation to the ejaculation process.
RESULTS:
Although acute treatment with the SSRIs fluoxetine and paroxetine immediately causes increased serotonin levels, delayed ejaculation does not occur. The increased serotonin levels induce oxytocin release via activation of 5-HT(1A) receptors, and this might compensate for the inhibitory actions of serotonin on sexual behavior. Chronic treatment with fluoxetine and paroxetine desensitizes 5-HT(1A) receptors on oxytocin neurons, and that might in part determine the onset of delayed ejaculation. Desensitization of 5-HT(1A) receptors is less strong following chronic treatment with the SSRIs fluvoxamine or citalopram, which may attenuate the degree of delayed ejaculation.
CONCLUSIONS:
Preliminary data suggest that the severity of chronic SSRI treatment-induced delayed ejaculation and the differences between the various SSRIs in inducing ejaculation delay is related to gradual desensitization of 5-HT(1A) receptors on oxytocin neurons.
Comment in
Post Justin on Fri Oct 14, 2011 6:14 am
I thought you might find this interesting given your theory and your condition. Oxytocin is released when we form love relationships. I don't know but perhaps this is related to why many people who seem to recover seem to do so when they allow themselves to date again. We'll see I'd do anything to recover!
Oxytocin involvement in SSRI-induced delayed ejaculation: a review of animal studies.
de Jong TR, Veening JG, Olivier B, Waldinger MD.
Source
Department of Psychopharmacology, Utrecht Institute of Pharmacological Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands.
Abstract
INTRODUCTION:
Selective serotonin reuptake inhibitors (SSRIs) differ in the severity of induced ejaculation delay. Various studies indicate that oxytocin is involved in sexual behavior.
AIM:
To review and evaluate the involvement of oxytocin in SSRI-induced ejaculation delay.
MAIN OUTCOME MEASURES:
Oxytocine release, 5-hydroxytryptamine (5-HT) neurotransmission, and desensitization of 5-HT(1A) receptors.
METHODS:
A review and critical analysis of animal studies investigating the interaction of serotonergic and oxytocinergic neurotransmission in relation to the ejaculation process.
RESULTS:
Although acute treatment with the SSRIs fluoxetine and paroxetine immediately causes increased serotonin levels, delayed ejaculation does not occur. The increased serotonin levels induce oxytocin release via activation of 5-HT(1A) receptors, and this might compensate for the inhibitory actions of serotonin on sexual behavior. Chronic treatment with fluoxetine and paroxetine desensitizes 5-HT(1A) receptors on oxytocin neurons, and that might in part determine the onset of delayed ejaculation. Desensitization of 5-HT(1A) receptors is less strong following chronic treatment with the SSRIs fluvoxamine or citalopram, which may attenuate the degree of delayed ejaculation.
CONCLUSIONS:
Preliminary data suggest that the severity of chronic SSRI treatment-induced delayed ejaculation and the differences between the various SSRIs in inducing ejaculation delay is related to gradual desensitization of 5-HT(1A) receptors on oxytocin neurons.
Comment in
Re: my research (Sonny)
Sonny on Fri Oct 14, 2011 7:28 am
That sounds exactly like what happened to me. That study suggests there may be differences in what sort of problems you have based on which drug you took. It could be that we are looking at different variations of PSSD. Well that gives me an idea for another poll. The drug that was taken, plus the symptoms one has.
I'll have to look into this further.
That sounds exactly like what happened to me. That study suggests there may be differences in what sort of problems you have based on which drug you took. It could be that we are looking at different variations of PSSD. Well that gives me an idea for another poll. The drug that was taken, plus the symptoms one has.
I'll have to look into this further.
Re: my research (Sonny)
Sonny on Fri Oct 14, 2011 7:38 am
From article on oxytocin:
The anxiolytic Buspar (buspirone) also appears to produce some or all of its effect via 5-HT1A receptor-induced oxytocin stimulation.
Buspar relieves all my symptoms, so this makes sense.
From article on oxytocin:
The anxiolytic Buspar (buspirone) also appears to produce some or all of its effect via 5-HT1A receptor-induced oxytocin stimulation.
Buspar relieves all my symptoms, so this makes sense.
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