Re: upregulation to reverse downregualtion???

[Guest guest]

same here , took lexapro for 9 month,quit, recovered after 4 month , then i took one pill of savella,only oneand now pssd for 1 year now.

 

Hi Man  I believe your theory , after quiting paxil ,which i took for 6 years i recovered after  3-4 months. Anxiety ans sexual pleasure came back. Than after 6 months I made a big mistake and tool lexapro because the shrink wanted me to, and now pssd.

To: SSRIsex Sent: Wednesday, June 6, 2012 12:47:17 AM

Subject: upregulation to reverse downregualtion???

 

We know that there is serotonin receptor down regulation due to overexposure to serotonin.

We know that there is serotonin receptor up regulation in people with chronically low levels of serotonin (such as suicidal and those that are clinically depressed).

Makes sense right? Too much of it, reduce the sensitivity. Not enough of it, increase the sensitivity.

Low levels actually making one more sensitive to drugs and high levels making one more tolerant.

In this case we have become so tolerant that we are tolerant to our own natural levels of serotonin.

Technically the serotonin receptors should up regulate on withdrawal of the drug but why should they if they are feeling the right amount of serotonin? They only up regulate if they are required to up regulate if the brain is feeling a lack of stimulation.

For example MDMA users will experience a huge influx of serotonin followed by down regulation and then massive serotonin depletion in the following weeks followed by a responsive up regulation. This is shown in studies with rats.

Ssris however work in a different fashion however jamming unnatural amounts in the synapse which our brains cannot immediately respond to which accounts for " start up " effects of massive down regulation in the first few weeks until the brain adapts. This explains why people may only get sexual dysfunction after multiple ssri exposures. Some people may get the same effect after one exposure- possible low receptor number to start with. And possible some individuals can go on and off the drugs with very little side effects due to naturally low serotonin- therefore receptor levels will bounce back.

So question is why aren't we trying to cause a sustained depletion of neurotransmitters to encourage up regulation of receptors???

As far as I can see there is only one drug that can cause this, a drug for high blood pressure Reserpine? Any thoughts on this?

Studies show it increases the response to other drugs such as lsd.

[Guest guest]

So what do you think the answers is, lower or increase serotonin. My shrink used to say we have to desensatize your sertonin receptor a bit so you have less anxiety. To: SSRIsex Sent: Friday, June 8, 2012

2:34:01 PM Subject: Re: upregulation to reverse downregualtion???

same here , took lexapro for 9 month,quit, recovered after 4 month , then i took one pill of savella,only oneand now pssd for 1 year now.

Hi Man I believe your theory , after quiting paxil ,which i took for 6 years i recovered after 3-4 months. Anxiety ans sexual pleasure came back. Than after 6 months I made a big mistake and tool lexapro because the shrink wanted me to, and now pssd.

To: SSRIsex Sent: Wednesday, June 6, 2012 12:47:17 AM

Subject: upregulation to reverse downregualtion???

We know that there is serotonin receptor down regulation due to overexposure to serotonin.

We know that there is serotonin receptor up regulation in people with chronically low levels of serotonin (such as suicidal and those that are clinically depressed).

Makes sense right? Too much of it, reduce the sensitivity. Not enough of it, increase the sensitivity.

Low levels actually making one more sensitive to drugs and high levels making one more tolerant.

In this case we have become so tolerant that we are tolerant to our own natural levels of serotonin.

Technically the serotonin receptors should up regulate on withdrawal of the drug but why should they if they are feeling the right amount of serotonin? They only up regulate if they are required to up regulate if the brain is feeling a lack of stimulation.

For example MDMA users will experience a huge influx of serotonin followed by down regulation and then massive serotonin depletion in the following weeks followed by a responsive up regulation. This is shown in studies with rats.

Ssris however work in a different fashion however jamming unnatural amounts in the synapse which our brains cannot immediately respond to which accounts for "start up" effects of massive down regulation in the first few weeks until the brain adapts. This explains why people may only get sexual dysfunction after multiple ssri exposures. Some people may get the same effect after one exposure- possible low receptor number to start with. And possible some individuals can go on and off the drugs with very little side effects due to naturally low serotonin- therefore receptor levels will bounce back.

So question is why aren't we trying to cause a sustained depletion of neurotransmitters to encourage up regulation of receptors???

As far as I can see there is only one drug that can cause this, a drug for high blood pressure Reserpine? Any thoughts on this?

Studies show it increases the response to other drugs such as lsd.

[Guest guest]

Desensitising receptors MAY (or may not) reduce anxiety. Anxiety is not just

caused by serotonin receptors, they may have nothing to do with it, your shrink

will not be able to prove this because in short nobody can, we're not that

advanced in understanding the brain. ADS make some people anxious as hell,

depends on your brain chemistry and what has gone wrong- these drugs take a stab

in the dark which can go wrong oh so often. The serotonin receptors are

responsible for many a function in the body, dulling and down regulating them

all would be like removing your soul. Who's to say anxiety isn't caused by a

million other different mechanisms in the brain? Basically what I'm saying is

down regulation is one of the major things causing persistent side effects

-otherwise antagonists would have the ability to prevent and block certain

symptoms. The idea is to cause a state in the brain where it would want to up

regulate the receptors to reach a new homeostatic set point instead of this new

one created with antidepressants. Serotonin/dopamine depletion would not be a

pleasant experience but it would make the brain respond/reverse the changes

hopefully. I can only find one drug that does this however.

>

>

> > 

> >Hi Man

> > 

> >I believe your theory , after quiting paxil ,which i took for 6 years i

recovered after  3-4 months. Anxiety ans sexual pleasure came back. Than after

6 months I made a big mistake and tool lexapro because the shrink wanted me to,

and now pssd.

> >

> >

> >

> >To: SSRIsex

> >Sent: Wednesday, June 6, 2012 12:47:17 AM

> >Subject: upregulation to reverse downregualtion???

> >

> >

> >

> > 

> >We know that there is serotonin receptor down regulation due to overexposure

to serotonin.

> >

> >We know that there is serotonin receptor up regulation in people with

chronically low levels of serotonin (such as suicidal and those that are

clinically depressed).

> >

> >Makes sense right? Too much of it, reduce the sensitivity. Not enough of it,

increase the sensitivity.

> >

> >Low levels actually making one more sensitive to drugs and high levels making

one more tolerant.

> >

> >In this case we have become so tolerant that we are tolerant to our own

natural levels of serotonin.

> >Technically the serotonin receptors should up regulate on withdrawal of the

drug but why should they if they are feeling the right amount of serotonin? They

only up regulate if they are required to up regulate if the brain is feeling a

lack of stimulation.

> >For example MDMA users will experience a huge influx of serotonin followed by

down regulation and then massive serotonin depletion in the following weeks

followed by a responsive up regulation. This is shown in studies with rats.

> >Ssris however work in a different fashion however jamming unnatural amounts

in the synapse which our brains cannot immediately respond to which accounts for

" start up " effects of massive down regulation in the first few weeks until the

brain adapts. This explains why people may only get sexual dysfunction after

multiple ssri exposures. Some people may get the same effect after one exposure-

possible low receptor number to start with. And possible some individuals can go

on and off the drugs with very little side effects due to naturally low

serotonin- therefore receptor levels will bounce back.

> >

> >So question is why aren't we trying to cause a sustained depletion of

neurotransmitters to encourage up regulation of receptors???

> >

> >As far as I can see there is only one drug that can cause this, a drug for

high blood pressure Reserpine? Any thoughts on this?

> >Studies show it increases the response to other drugs such as lsd.

> >

> >

> >

> >

>

[Guest guest]

NO going back on the drug should 100% make things worse. Haha I'm not sure a

coma would do much or know anything about how it effects neurotransmitters.

> > >

> > >

> > > > 

> > > >Hi Man

> > > > 

> > > >I believe your theory , after quiting paxil ,which i took for 6 years i

recovered after  3-4 months. Anxiety ans sexual pleasure came back. Than

after 6 months I made a big mistake and tool lexapro because the shrink wanted

me to, and now pssd.

> > > >

> > > >

> > > > From: kirby.lancaster <kirby.lancaster@>

> > > >To: SSRIsex

> > > >Sent: Wednesday, June 6, 2012 12:47:17 AM

> > > >Subject: upregulation to reverse downregualtion???

> > > >

> > > >

> > > >

> > > > 

> > > >We know that there is serotonin receptor down regulation due to

overexposure to serotonin.

> > > >

> > > >We know that there is serotonin receptor up regulation in people with

chronically low levels of serotonin (such as suicidal and those that are

clinically depressed).

> > > >

> > > >Makes sense right? Too much of it, reduce the sensitivity. Not enough of

it, increase the sensitivity.

> > > >

> > > >Low levels actually making one more sensitive to drugs and high levels

making one more tolerant.

> > > >

> > > >In this case we have become so tolerant that we are tolerant to our own

natural levels of serotonin.

> > > >Technically the serotonin receptors should up regulate on withdrawal of

the drug but why should they if they are feeling the right amount of serotonin?

They only up regulate if they are required to up regulate if the brain is

feeling a lack of stimulation.

> > > >For example MDMA users will experience a huge influx of serotonin

followed by down regulation and then massive serotonin depletion in the

following weeks followed by a responsive up regulation. This is shown in studies

with rats.

> > > >Ssris however work in a different fashion however jamming unnatural

amounts in the synapse which our brains cannot immediately respond to which

accounts for " start up " effects of massive down regulation in the first few

weeks until the brain adapts. This explains why people may only get sexual

dysfunction after multiple ssri exposures. Some people may get the same effect

after one exposure- possible low receptor number to start with. And possible

some individuals can go on and off the drugs with very little side effects due

to naturally low serotonin- therefore receptor levels will bounce back.

> > > >

> > > >So question is why aren't we trying to cause a sustained depletion of

neurotransmitters to encourage up regulation of receptors???

> > > >

> > > >As far as I can see there is only one drug that can cause this, a drug

for high blood pressure Reserpine? Any thoughts on this?

> > > >Studies show it increases the response to other drugs such as lsd.

> > > >

> > > >

> > > >

> > > >

> > >

> >

>

[Guest guest]

I want to add something to what I've said below. The studies that I mention show

that certain serotonin receptors have an excitory role in arousal, and others

inhibit arousal. That part is true, but what I recommended is probably the

opposite of what we should do to fix the problem in the long run. Let me

explain.

Look at these 3 serotonin receptor sub-types that are known to be involved in

arousal. They are involved in the mice studies mentioned below. Some inhibit

arousal, and some increase arousal.

5HT1A receptor - inhibits arousal.

5HT2A receptor - increases arousal

5HT2C receptor - inhibits arousal.

I suggested in my last post that we should agonize the ones that increase

arousal, and antagonize the ones that inhibit arousal. Makes sense. However, if

we assume that people with this condition have " down-regulated " certain

receptors (because of too much serotonin), and we want to reverse the process,

or " up-regulate " those receptors, then we have to antagonize the receptors we

want to up-regulate, so that our bodies react " in opposition " by making those

receptors more sensitive.

The 5H%2A receptor is probably the culprit here. If we assume that

" down-regulation, " (which is the natural result of too much serotonin), is the

problem, then it's only the " excitory " receptors that we have to worry about

because " down-regulation " will only have a negative effect on arousal if we are

down-regulating an excitory receptor. (after all, if we down-regulate a

receptors that inhibits arousal that's not going to kill arousal - it's probably

going to increase it).

The serotonin receptors that increase arousal (according to mice studies)are the

following:

5HT2A and 5HT3

The receptors that inhibit arousal are:

5HT1A and 5HT2C

This actually does fit with my experience perfectly. I have taken the following

drugs, for periods of time, with the following results:

Flibanserin (5HT1A Agonist, 5HT2A antagonist) - One dose absolutely killed my

drive, which is exactly what you would expect! I'm " agonizing " an inhibitory

receptor and " antagonizing " one that causes arousal. My drive died so fast I

couldn't believe it. I went from 25% to 5% almost instantly. That's the

short-run effect. I stopped taking the Flibanserin after just a couple of doses

because the total loss of libido scared me.

Lecozotan (5HT1A antagonist) - in the short run, this definitely increased by

ability to become aroused, but not too much. Makes sense. I'm " turning off " a

receptor that inhibits arousal. But not doing anything to the receptors that

increase arousal.

Dimebon - (5HT2C antagonist) - exact same effect as above, in the short run.

The Lecozotan and the Dimebon I took for 8 days each. AFTER 8 DAYS, they began

to have a negative effect on arousal. This fits with the idea that my body was

reacting against the " antagonist " by up-regulating these inhibitory

neuro-transmitters, and thus inhibiting arousal further.

By the way, I've also noticed a significant up-tick in libido and arousal by

taking methylphenydate (ritalin). Among other things like boosting dopamine and

norepinephrine, this drug is a 5HT2A agonist. In the short run, this really

helps libido. In the long run, it probably makes the body down-regulate that

serotonin receptor further, and makes the problem worse. But my experience fits

very nicely with the theory that the 5HT2A receptor excites arousal, and

therefore is probably the one that has been down-regulated out of a job, and

most needs to be fixed.

I thought Flibanserin was a bad thing, but it's exactly the drug that I would

hypothesize will make the biggest difference in the long run. In the short run,

it feels like you've been castrated. In the long run, it might fix things by

causing the body to " up-regulate " the 5HT2A receptor, which is the real problem.

At any rate, I believe that the culprit is the down-regulated 5HT2A receptor,

which is notoriously hard to up-regulate, from what I've been told by people who

have lost their libido by taking ecstasy. Interesting.

I'll post more about " up-regulating " the 5HT2A receptor later. People who have

tried it have had mixed results, but some people who have had a positive effect

have used 5HT2A receptor antagonists to up-regulate this receptor in the long

run. I have heard some success stories from these drugs below, which do exactly

this:

mirtazapine

nefazodone

All this is wild speculation, you realize. At the end of the day, it's a black

box, and I don't know what would really happen if I took, say, Flibanserin, for

a couple of months, letting my sex drive die, and then hoping my body

up-regulated back to normal in response. I talk tough, but when I take these

drugs, and my 25% immediately dies, I don't really have the guts to finish the

moth-long trial to see what happens. At some point, we're going to have to do

some human trials though . . .

> > > >

> > > > We know that there is serotonin receptor down regulation due to

overexposure to serotonin.

> > > >

> > > > We know that there is serotonin receptor up regulation in people with

chronically low levels of serotonin (such as suicidal and those that are

clinically depressed).

> > > >

> > > > Makes sense right? Too much of it, reduce the sensitivity. Not enough of

it, increase the sensitivity.

> > > >

> > > > Low levels actually making one more sensitive to drugs and high levels

making one more tolerant.

> > > >

> > > > In this case we have become so tolerant that we are tolerant to our own

natural levels of serotonin.

> > > > Technically the serotonin receptors should up regulate on withdrawal of

the drug but why should they if they are feeling the right amount of serotonin?

They only up regulate if they are required to up regulate if the brain is

feeling a lack of stimulation.

> > > > For example MDMA users will experience a huge influx of serotonin

followed by down regulation and then massive serotonin depletion in the

following weeks followed by a responsive up regulation. This is shown in studies

with rats.

> > > > Ssris however work in a different fashion however jamming unnatural

amounts in the synapse which our brains cannot immediately respond to which

accounts for " start up " effects of massive down regulation in the first few

weeks until the brain adapts. This explains why people may only get sexual

dysfunction after multiple ssri exposures. Some people may get the same effect

after one exposure- possible low receptor number to start with. And possible

some individuals can go on and off the drugs with very little side effects due

to naturally low serotonin- therefore receptor levels will bounce back.

> > > >

> > > > So question is why aren't we trying to cause a sustained depletion of

neurotransmitters to encourage up regulation of receptors???

> > > >

> > > > As far as I can see there is only one drug that can cause this, a drug

for high blood pressure Reserpine? Any thoughts on this?

> > > > Studies show it increases the response to other drugs such as lsd.

> > > >

> > >

> >

>

[Guest guest]

An interesting post but keep away from nefazodone: this drug caused my

PSSD and a whole load of other brain damage too where I didn't stop

twitching for two years after stopping it. It also felt like my body was

full of tiny insects crawling through my body and I kept getting cramp

in my hands and feet. I was terified for months on end but when it the

worst of it started to slowly subsise I began to calm down a bit

although my sex drive never returned. Other people have got PSSD from

taking nefazodone and there is a scientific medicle article about this

out there on the web this somewhere.

My own feeling is that some of our receptors have been down regulated

but the brain cells are still there or not completetley ruined. This

gives me hope that recovery is still possible.

Kv

> > > > >

> > > > > We know that there is serotonin receptor down regulation due

to overexposure to serotonin.

> > > > >

> > > > > We know that there is serotonin receptor up regulation in

people with chronically low levels of serotonin (such as suicidal and

those that are clinically depressed).

> > > > >

> > > > > Makes sense right? Too much of it, reduce the sensitivity. Not

enough of it, increase the sensitivity.

> > > > >

> > > > > Low levels actually making one more sensitive to drugs and

high levels making one more tolerant.

> > > > >

> > > > > In this case we have become so tolerant that we are tolerant

to our own natural levels of serotonin.

> > > > > Technically the serotonin receptors should up regulate on

withdrawal of the drug but why should they if they are feeling the right

amount of serotonin? They only up regulate if they are required to up

regulate if the brain is feeling a lack of stimulation.

> > > > > For example MDMA users will experience a huge influx of

serotonin followed by down regulation and then massive serotonin

depletion in the following weeks followed by a responsive up regulation.

This is shown in studies with rats.

> > > > > Ssris however work in a different fashion however jamming

unnatural amounts in the synapse which our brains cannot immediately

respond to which accounts for " start up " effects of massive down

regulation in the first few weeks until the brain adapts. This explains

why people may only get sexual dysfunction after multiple ssri

exposures. Some people may get the same effect after one exposure-

possible low receptor number to start with. And possible some

individuals can go on and off the drugs with very little side effects

due to naturally low serotonin- therefore receptor levels will bounce

back.

> > > > >

> > > > > So question is why aren't we trying to cause a sustained

depletion of neurotransmitters to encourage up regulation of

receptors???

> > > > >

> > > > > As far as I can see there is only one drug that can cause

this, a drug for high blood pressure Reserpine? Any thoughts on this?

> > > > > Studies show it increases the response to other drugs such as

lsd.

> > > > >

> > > >

> > >

> >

>