SSRI, PGAD and Acetylcholine

[Shadow]

So, a worsening of my condition led me to think about something. Let me explain the situation first:

After a week of being off SSRI, I was striked with a very weird sensation on the right side of my pelvic area(from the glans to the buttock), something like an itch in the nerves. I felt the exact same sensation on every nerve of the body but with a lesser intensity, on my left leg it felt like restless leg syndrome. After 7 months, the pelvic feeling pretty much subsided, but this week it returned, but this time on the left side of my pelvic area, and the restless leg feeling diminished. Interesting fact about this is that before this torture started again, my erections became better.

This sensation, when in genitals is called PGAD(Persistent Genital Arousal Disorder) but dont let the "arousal" fool you, it has nothing to do with being horny. This condition is more common in females, on post-menopausal women the condition can appear after hormonal treatment, and in general after SSRIs use. A study showed a connection of PGAD and Restless Leg Syndrome.

So what this have to do with Acetylcholine?

First, when pre-ssri, sometimes I used to take an Orphenadrine + Caffeine pill because of a bad neck. One of the thing that I noticed doing this was that I had the same Restless Leg feeling that I started to experience after ssri. Orphenadrine is an ANTICHOLINERGIC drug.

There was a case of PGAD which the symptoms improved after the use of Verenicline, an agonist of some NICOTINIC ACETHYLCHOLINE RECEPTORS.

Varenicline displays full agonism on α7 nicotinic acetylcholine receptors and is a partial agonist on the α4β2, α3β4, and α6β2 subtypes. In addition, it is a weak agonist on the α3β2 containing receptors.
Varenicline's partial agonism on the α4β2 receptors rather than nicotine's full agonism produces less effect of dopamine release than nicotine's. This α4β2 competitive binding reduces the ability of nicotine to bind and stimulate the mesolimbic dopamine system - similar to the method of action of buprenorphine in the treatment of opioid addiction.

Acetylcholine and SSRIs

There is an inverse, antagonistic relationship between acetycholine (ACh) and serotonin (SE) in the brain. In other words as the quantity of one increases, the quantity of the other decreases. A certain amount of ACh is necessary for normal, optimal brain function. Memory, motivation, higher-order thought processes, sexual desire and activity, and sleep (among other things) depend on ACh. In lower amounts, ACh can act like a stimulant by releasing norepinephrine (NE) and dopamine (DA). However, those brain chemicals are used up (depleted) in the process; and a deficiency can occur. Too much ACh relative to other brain chemicals such as SE, NE, and DA has an adverse effect on brain function. This is because in larger quantities ACh acts like an inhibitory neurotransmitter, causing increased nervous system inhibition (depression). Important to remember is that, in general, as ACh levels go up in the brain, the levels of the other brain transmitters go down.

Symptoms of High Acetylcholine

The Role of Acetylcholine Mechanisms in Affective Disorders

Low Acetylcholine Symptoms by @Area-1255

Progesterone and Acetylcholine

Progesterone modulates a neuronal nicotinic acetylcholine receptor.

The major brain nicotinic acetylcholine receptor is assembled from two subunits termed alpha 4 and n alpha 1. When expressed in Xenopus oocytes, these subunits reconstitute a functional acetylcholine receptor that is inhibited by progesterone levels similar to those found in serum.

Progesterone as a neuroactive neurosteroid, with special reference to the effect of progesterone on myelination

Some steroids are synthesized within the central and peripheral nervous system, mostly by glial cells. These are known as neurosteroids. In the brain, certain neurosteroids have been shown to act directly on the function of membrane receptors for neurotransmitters. For example, progesterone inhibits the neuronal nicotinic acetylcholine receptor, whereas its 3oc ,5oc reduced metabolite 3oc, 5a-tetrahydroprogesterone (allopregnanolone) activates the y-aminobutyric acid receptor complex A (GABA-RA).

 

[Canari]

How do you react to tobaco? Nicotine goes to the acethylcholine receptors, which then multiply accordingly. So I guess smoking would "make something"....

 

[Shadow]

How do you react to tobaco? Nicotine goes to the acethylcholine receptors, which then multiply accordingly. So I guess smoking would "make something"....

I never smoked hehehe

 

[Area-1255]

Thanks for referencing my post, Shadow. I agree Acetylcholine is a big part of the picture, however there are also studies that show that ACh can be detrimental in modest amounts in terms of its inhibition of dopamine (by muscarinic receptors). There are many reports of anticholinergic like dicyclomine enhancing libido in Men.
--> Yahoo! Answers Anticholinergic Caused Euphoria High Libido
--> Psychotropics and sexual dysfunction
--> Prescribing to Preserve Sexual Function
--> Longecity Post
--> Acetylcholine and Depression

Originally my thought process was that anticholinergics *might* not be a good thing for erectile function given the mammal studies show that. I think to some degree that's true.
However, I believe that some of the anecdotal "benefits" of say CDP-Choline are dopamine-related. Also, its consistent with my experiments, because I've noticed that anticholinergics do not necessarily impact any sexual function negatively. In fact, some of them tended to increase libido. That would be, hyoscyamine and dicylcomine.

The thing is though is that it depends on whether the anticholinergic in question possesses high indiscriminative binding. Meaning, it is JUST as capable to binding to blood vessels and the heart etc as it is the Brain - in which case, side-effects might be worse than with simpler chemicals.

Regarding the core subject and hypothesis of this post...I would agree Nicotinic receptors play a role, perhaps a facilitative role on libido, but since Nicotine is a vasoconstrictor then things like Wellbutrin (Bupropion) would have putative vasodilating properties.

 

[Shadow]

Interesting @Area-1255, you have nice posts in your website.

After all, I think that the receptors at the spinal cord are the responsible. What is hard to understand is why this happens only AFTER stoping the drugs. Any ideia @gbolduev ?

I may be one of the worsts post ssri cases... I dont know how im still alive!

 

[Area-1255]

Interesting @Area-1255, you have nice posts in your website.

After all, I think that the receptors at the spinal cord are the responsible. What is hard to understand is why this happens only AFTER stoping the drugs. Any ideia @gbolduev ?

I may be one of the worsts post ssri cases... I dont know how im still alive!

What symptoms are unresolved and what have you tried so far?

 

[Area-1255]

We have an article on High Acetylcholine as well btw.
Symptoms of High Acetylcholine Levels.

 

[Shadow]

What symptoms are unresolved and what have you tried so far?

Symptoms
https://hackstasis.com/forums/-/list

The "Obnoxious genital nerve problem(improved)" is the pgad, that came back this week...

I tried Inositol only, I have too much symptoms, that made me crazy on what to try first... I have a fear of making my tinnitus worse

 

[Canari]

We have an article on High Acetylcholine as well btw.
Symptoms of High Acetylcholine Levels.

These symptoms are of para-sympathetic dominance. Nerves are what give the command to the release of neurotransmittors. That is why we can modify the physiology through many methods that human beings have found out since ancient times...

 

[Area-1255]

These symptoms are of para-sympathetic dominance. Nerves are what give the command to the release of neurotransmittors. That is why we can modify the physiology through many methods that human beings have found out since ancient times...

Acetylcholine (in excess) CAUSES "parasympathetic dominance" as you say - its the main parasympathetic ganglionic neurotransmitter.

 

[Canari]

Acetylcholine (in excess) CAUSES "parasympathetic dominance" as you say - its the main parasympathetic ganglionic neurotransmitter.

No, there is a feedback loop but nerves come first, and this is not enough studied.
Even when there is anything such as drugs or lack of nutrients, this is an agression to the body, and the body react with nerves.
How do you think we can react so fast through the nervous system and think that neurotransmitters come first and cause the nerves to react? Excess acethylcholline is a consequence.

 

[Area-1255]

No, there is a feedback loop but nerves come first, and this is not enough studied.
Even when there is anything such as drugs or lack of nutrients, this is an agression to the body, and the body react with nerves.
How do you think we can react so fast through the nervous system and think that neurotransmitters come first and cause the nerves to react? Excess acethylcholline is a consequence.

Well there might be a "reaction" but there are also plenty of individual experiences who, in addition to the research on Acetylcholine and Depression - experience Anhedonia when using too much Cholinergic stuff.

 

[Area-1255]

And by that I mean that the cholinergic sups would have to "cause" that reaction. What we are talking about here is also likely related to C-reactive protein (inflammation) and the adrenals.

 

[Canari]

Of course you can "do the job" of the ANS and manipulate the chemicals.... But it does not mean that it was not caused first hand by the ANS! There are hundreds of chemicals and thousands of reactions in the body, and the body is intelligent enough to be regulating all this alone, even when you have some intervention on the body with drugs.

If you do not care of the master of the body, you do not gain resilience, and you will be more likely to not resist to further stresses. If you care of the nerves, then your body regulates better the endocrine system.

Almost no scientist gets this in its education! I have studied this, and doctors in the course all said they knew nothing about it before the course! When people speak of the nervous system and adrenaline and acethycholine, well, then do not speak about the nervous system AT ALL! Nerves are nerves, and neurotransmitters are releised in the blood!

 

[Canari]

What we are talking about here is also likely related to C-reactive protein (inflammation) and the adrenals.

Not adrenals but the sympathetic system. When there is a freeze response, this is caused by the vagus, parasympathetic. But the sympathetic system is also active underneath, it is just blocked. The sympathetic nervous system triggers adrenaline, thus adrenals.
What is complicated is that the freeze response is not only freeze, as it is also responsible of sensations of bliss or being part of the "everything", thus all the extasis experiences! Most people in the so called woo-woo trend are people who experienced this sort of dissociation and meditate to "go away" instead of being present. But of course it is thus understandable that science despises this! And if you use meditation for dissociating more, well you might feel better, but from not feeling, and it will solve nothing long term.

Social engagement is also caused by the vagus nerve, but by the other branch of the vagus. The 2 branches do not work at the same time, this is why connexion is difficult when you are in a freeze state, and nevertheless, without connexion, it is very difficult to come out of freeze.

With SSRI, at least labs earn some more money... and they can finance reasearch only about chemicals!

SSRI blocks down the road, at neurotransmitters level, but does not block the nervous system, so it can still go awry. And when you go out of a freeze response, the problem is that you find the activation of the sympathetic fight and flight response still on fire! The freeze BLOCKS it, but do not extinguishes it. Depression is when you are frozen or dissociated. Anxiety is when the sympathetic activation shows (when the freeze is less present).

It is difficult but not impossible to solve. The problem is to remove little of the freeze, just to let go part of the sympathetic activation. And do it again and again. Do not replace biological protocols, but at least add some nerves regulation to it!

 

[Canari]

If you do not believe me, just have a look at this page...
https://hackstasis.com/forums/-/list

 

[Area-1255]

If you do not believe me, just have a look at this page...
https://hackstasis.com/forums/-/list

I did not say I didn't believe you. There is some merit to what you are saying. What I was referring to is that if there is an EXCESS of ANY NEUROTRANSMITTER, there can be increased oxidative stress which can lead to increased CRP levels which then affects the mitochondria, adrenals etc. At some point, the Sympathetic Nervous System becomes haywire in these imbalances. A point that justifies both of our comments.

 

[Canari]

In FB group about the nervous system, I keep telling some people to also go the balancing route, as some believe in only personal work and meditation etc, and here I keep telling to add some direct nervous system work! Because i believe both routes complement each other.
Maybe some people think that it is not possible to work directly at nerve level? Or that there is no protocol? Yes and no... There is no other route than learning and feeling in us how it works, and when you know how it works, you can do something and self-regulate and regulate others too. Even when you know noting, your body still do it! But when you know more, you can enhance this and get more positive effects. Anxiety is a charge of fear. Fear comes from unsuccessful escape. The body memory does not know time, so it still seems present even when it is past.

Acethylcholine is a protection, because it blocks/immobilize the fear/flight activation, before "the circuit burns". So it freezes the anxiety most of the time, so that it does not become permanent. But in depression you feel heavy, down, contracted. But it is better than opening the box and let go all the activation at once! I have twice let go too much at a time, and it resulted in convulsions! Each time it happened because my system was intelligent enough to do it when some therapists were around.... And once I called a friend to help with a session by phone because I thought I was dying. I had not slept for 3 nights and was unable to even drink! 1 hour later I was taking a shower and then eating... 1 hour is what it took us to make me come back to my body... Alone I could not. By phone we could do it because i know the process and could give her the informations she needed.
I have also already made people come back from anxiety to feeling good in 1 hour. It is not fixed forever because the body needs to re-build the habit and stabilize it.

When there are things like toxic stuff in the body, of course we need to remove the threat, and also rebalance the body when possible. BUT the digestive system and the immune system both only work in a parasympathetic state! So we need to balance the nerves at this level, upstream, to help the body reacts better to any balancing.