I am going to drop a major bomb soon

This is for hypothesis and even educated speculation.
MindChanger
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Re: I am going to drop a major bomb soon

Unread post by MindChanger »

heymartinn wrote: Mon Sep 06, 2021 7:22 pm
cdraham wrote: Mon Sep 06, 2021 6:48 pm
MindChanger wrote: Mon Sep 06, 2021 6:40 pm DXM nay have an influence on 5HT1A (not sure whether presynaptic tho) or at least its G-coupled protein.

"A high dose of DM significantly produced serotonin syndrome in mice. In addition, treatment with DM resulted in a significant increase in 5-HT1A receptor mRNA expression" (https://academic.oup.com/ijnp/article/1 ... 49/2946757).

"These results suggest that DM may inhibit the G-protein coupled inwardly rectifying K(+) channels" (https://pubmed.ncbi.nlm.nih.gov/10974313/).

But it is too dirty to know for sure.
Yes, sigma agonism also looks interesting, bc it regulates serotonin receptors.
What's your guys thoughts on fenclonine? In theory, wouldn't lowering serotonin for at least 4 weeks would result in pre-synaptic upregulation? or any other positive un-doing of what SSRI's has done?
I think that more trials are needed. As PSSD is a very rare condition, our response to fenclonine can be unpredictable. I have not seen anyone taking it regularly for a period longer than 2 weeks from a reputable source; a majority stops it too early due to anxiety and other side-effects.
cdraham
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Re: I am going to drop a major bomb soon

Unread post by cdraham »

guacamo wrote: Sat Sep 04, 2021 5:43 pm SSRI also can cause genital shrinkage so from the theory that PSSD is a some of SSRI's side effects which still persist after the treatment, then yes, it is very much possible.
I don't think pssd is just some ssris side effects that persist after discontinuation. I think it triggers some whole different condition in some. I didn't have muscle atrophy or genital shrinkage while beeing on ssris. It came after I cold turkeyed for the second time. Imo the withdrawal should be more looked at.

How can u explain people not responding to hormones and muscle atrophy by 5ht1a autoreceptor dysfunction. 0
sovietxrobot
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Re: I am going to drop a major bomb soon

Unread post by sovietxrobot »

cdraham wrote: Tue Sep 07, 2021 1:43 pm
guacamo wrote: Sat Sep 04, 2021 5:43 pm SSRI also can cause genital shrinkage so from the theory that PSSD is a some of SSRI's side effects which still persist after the treatment, then yes, it is very much possible.
I don't think pssd is just some ssris side effects that persist after discontinuation. I think it triggers some whole different condition in some. I didn't have muscle atrophy or genital shrinkage while beeing on ssris. It came after I cold turkeyed for the second time. Imo the withdrawal should be more looked at.

How can u explain people not responding to hormones and muscle atrophy by 5ht1a autoreceptor dysfunction. 0
I've researched PSSD almost exclusively through the lens of an acute withdrawal disorder. There are many classes of drugs, SSRI included, that can have rebound effects on withdrawal- meaning the original symptoms return but more severely. The difference in symptoms across PSSD sufferers may due to which particular receptors are 'rebounding' and to what degree- likely determined by an interaction of environment, medication, and underlying genetics.
cdraham
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Re: I am going to drop a major bomb soon

Unread post by cdraham »

sovietxrobot wrote: Tue Sep 07, 2021 4:04 pm
cdraham wrote: Tue Sep 07, 2021 1:43 pm
guacamo wrote: Sat Sep 04, 2021 5:43 pm SSRI also can cause genital shrinkage so from the theory that PSSD is a some of SSRI's side effects which still persist after the treatment, then yes, it is very much possible.
I don't think pssd is just some ssris side effects that persist after discontinuation. I think it triggers some whole different condition in some. I didn't have muscle atrophy or genital shrinkage while beeing on ssris. It came after I cold turkeyed for the second time. Imo the withdrawal should be more looked at.

How can u explain people not responding to hormones and muscle atrophy by 5ht1a autoreceptor dysfunction. 0
I've researched PSSD almost exclusively through the lens of an acute withdrawal disorder. There are many classes of drugs, SSRI included, that can have rebound effects on withdrawal- meaning the original symptoms return but more severely. The difference in symptoms across PSSD sufferers may due to which particular receptors are 'rebounding' and to what degree- likely determined by an interaction of environment, medication, and underlying genetics.
I've looked at this from a different angle. I asked myself what if ssris triggered something else. I came to the conclusion SSRIs can potentially work as corticosteroids and surpress the immune system.

Do you know what happens when someone infected with borrelia (asymptomatic) gets a cortisone injection? Lyme goes into his CNS and he now has neurological lyme disease. The immune system kept the bacteria in check, but when severely compromised, the bacteria spread in the brain etc.

I think similiar stuff could have happened to some of us.
cdraham
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Re: I am going to drop a major bomb soon

Unread post by cdraham »

sovietxrobot wrote: Tue Sep 07, 2021 4:04 pm
cdraham wrote: Tue Sep 07, 2021 1:43 pm
guacamo wrote: Sat Sep 04, 2021 5:43 pm SSRI also can cause genital shrinkage so from the theory that PSSD is a some of SSRI's side effects which still persist after the treatment, then yes, it is very much possible.
I don't think pssd is just some ssris side effects that persist after discontinuation. I think it triggers some whole different condition in some. I didn't have muscle atrophy or genital shrinkage while beeing on ssris. It came after I cold turkeyed for the second time. Imo the withdrawal should be more looked at.

How can u explain people not responding to hormones and muscle atrophy by 5ht1a autoreceptor dysfunction. 0
I've researched PSSD almost exclusively through the lens of an acute withdrawal disorder. There are many classes of drugs, SSRI included, that can have rebound effects on withdrawal- meaning the original symptoms return but more severely. The difference in symptoms across PSSD sufferers may due to which particular receptors are 'rebounding' and to what degree- likely determined by an interaction of environment, medication, and underlying genetics.
How can 1 pill cases be explained by this model? How can people severely crash from 1 pill into bedridden zombie fatigue state? I doubt this can be explained by 5ht1a.

Do you even get severe withdrawal from 1 pill? No. Does cortisol rise from 1 pill? Yes
Tree
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Re: I am going to drop a major bomb soon

Unread post by Tree »

cdraham wrote: Tue Sep 07, 2021 4:47 pm
sovietxrobot wrote: Tue Sep 07, 2021 4:04 pm
cdraham wrote: Tue Sep 07, 2021 1:43 pm

I don't think pssd is just some ssris side effects that persist after discontinuation. I think it triggers some whole different condition in some. I didn't have muscle atrophy or genital shrinkage while beeing on ssris. It came after I cold turkeyed for the second time. Imo the withdrawal should be more looked at.

How can u explain people not responding to hormones and muscle atrophy by 5ht1a autoreceptor dysfunction. 0
I've researched PSSD almost exclusively through the lens of an acute withdrawal disorder. There are many classes of drugs, SSRI included, that can have rebound effects on withdrawal- meaning the original symptoms return but more severely. The difference in symptoms across PSSD sufferers may due to which particular receptors are 'rebounding' and to what degree- likely determined by an interaction of environment, medication, and underlying genetics.
How can 1 pill cases be explained by this model? How can people severely crash from 1 pill into bedridden zombie fatigue state? I doubt this can be explained by 5ht1a.

Do you even get severe withdrawal from 1 pill? No. Does cortisol rise from 1 pill? Yes
I do. These drugs are very powerful and dangerous obviously. I think we can say we underestimated the potential dangers of these drugs. You probably can get withdrawal side effects from one pill. There could be substantial sert dysregulation after one pill in some people that doesn't normalize after withdrawal which would desensitize receptors. I wouldn't dismiss anything at this point especially how my life has turned out. All I know is these drugs are not safe and extremely understudied. My cortisol levels are normal yet I'm in this debilitating veggie state.
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guacamo
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Re: I am going to drop a major bomb soon

Unread post by guacamo »

I would like to clarify that i do not think that taking 5-HT1A agonists will cure pssd, i just wanted to state that 5-HT1A agonism was common occurence during many recovery stories, why sometimes it was part of the recovery, and why it only works in some cases, I do not know. I would believe it has to include some interplay between serotonin receptors.
sovietxrobot
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Re: I am going to drop a major bomb soon

Unread post by sovietxrobot »

cdraham wrote: Tue Sep 07, 2021 4:10 pm I've looked at this from a different angle. I asked myself what if ssris triggered something else. I came to the conclusion SSRIs can potentially work as corticosteroids and surpress the immune system.

Do you know what happens when someone infected with borrelia (asymptomatic) gets a cortisone injection? Lyme goes into his CNS and he now has neurological lyme disease. The immune system kept the bacteria in check, but when severely compromised, the bacteria spread in the brain etc.

I think similiar stuff could have happened to some of us.
Its entirely likely that PSSD is caused by more than receptor dysfunction alone. We see people who have many androgenic symptoms similar to PFS, for instance.
sovietxrobot
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Re: I am going to drop a major bomb soon

Unread post by sovietxrobot »

cdraham wrote: Tue Sep 07, 2021 4:47 pm How can 1 pill cases be explained by this model? How can people severely crash from 1 pill into bedridden zombie fatigue state? I doubt this can be explained by 5ht1a.

Do you even get severe withdrawal from 1 pill? No. Does cortisol rise from 1 pill? Yes
I dont have a great explanation for that, which is why I have focused on the withdrawal model. My speculative guess is that people have different levels of sensitivity to SSRI which dictates their withdrawal response. Some people quit abruptly with no side effects, other gets side effects but recover. Those of us who are very sensitive get permanent symptoms, and those who are the most sensitive trigger a rebound response from just a single dose.

I'm not sold on 5HT1A theory.
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guacamo
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Re: I am going to drop a major bomb soon

Unread post by guacamo »

I just wanna say that my trial is going very well, I enjoy music, I enjoy sex, I enjoy playing games and in general i enjoy life, and I improve day by day. Before i was very bored and anhedonic.
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