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Restoring Sensitivity to Meds, Herbs, and Supplements?

choline acetylcholine sensitivity dopamine

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#1 dk2011

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Posted 28 March 2020 - 03:02 AM


In December of 2017, I posted here a long thread about an issue I'm having, and it still isn't resolved.  However, I do have new data, and I need help.
 
Background:
I have some disorder that involves a possible blend of or similarities to the following:

  • Dysautonomia
  • POTS Syndrome (Postural Orthostatic Tachycardia Syndrome)
  • Chronic Fatigue Syndrome
  • MCAS (Mast Cell Activation Syndrome)
  • ADHD

My understanding is that all of these involve an overactive Fight-or-Flight Sympathetic Nervous system.
 
Obviously, my "system" does not balance itself out...  
 
 
My current problem:
As a kid I used to be super sensitive to medications, herbs, and supplements and persisted for over a decade.  Small doses of herbs or meds would act as if I took massive amounts. More recently, I used cholinergic based supplements such as Choline Bitartrate, CDP-Choline (Citicoline), and other Acetylcholine boosters, which not only reversed my hyper-responsiveness and sensitivity to meds, but it left me extremely fatigued with no energy and virtually unresponsive to supplements, herbs, and meds.  I'm no longer sensitive anymore to supplements, and most supplements doesn't even seem like they work anymore.  It's a problem, because it left me permanently fatigued 24/7 and it makes me virtually unable to work due to constant exhaustion.
 
On my previous thread from December 2017,  which I didn't bump since it was poorly worded, many users seemed very close to solving my problem.
 

Here's what's new:
Very recently, a user messaged me and said he had the same problem, but only the opposite.  And said he resolved it completely.

Hey did you ever figure out how to rebalance? I feel I have gone through the same. Except the opposite. I use to never get effects from herbs or medications until I started using dopaminergics. I stayed in that more dopamine oriented brain for nearly two years. I was able to rebalance to a acytelcholine dominant brain after using alpha gpc.[/size]

 
He said he reversed it by using things like:  

Forskolin ( the best but need to find a decent vendor I use barlowes) Catuaba bark Polygala Cordyceps Muncuna puriens[/size]

 

polygala. NAC did provide temporary relief.[/size]

 
 
It's obviously an important clue, but I also do not want to start putting random herbal supplements in my system without a better understanding.  Any theories?  And am I going to try Polygala or Forskolin or what?  Isn't there a simpler supplement or remedy that would reverse this issue?



#2 kurdishfella

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Posted 28 March 2020 - 08:11 AM

Your metabolism slows down as you age maybe that could be it. You need metabolism to process it obviously but if it is not working properly it could hinder the effects of drugs.



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#3 DaveX

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Posted 28 March 2020 - 10:35 PM

Chronic fatigue syndrome can have to do with NMDA-receptors. Maybe also the dopamine-system, I wonder. For NMDA, Magnesium-L-Threonate comes to mind for me. 

Mast Cell Activation Syndrome can be addressed with various things, and it doesn't necessarily affect neuronal activity. I don't know about the pathological "syndrome", but I've also been told I might have such issues when I react well to something like Quercetin, Astragalus, Omega 3, and I have allergies anyway. You can also try an antihistamine which doesn't cross the blood-brain-barrier if you want to avoid getting tired. Quercetin can have tiring (or whatever) mental effects over time though, and so can Astragalus. At first you might like them.

 

I can't really wrap my head around how an acetylcholine-dopamine switch affects sensitivity to medicine or supplements. It seems overfunctioning acetylcholine would also have way more and maybe different symptoms than you have. Who knows.

 

I usually liked Forskolin as an additive to other things. It activates cAMP in neurons (whatever that does, it's supposed to be good) and oxytocin, which can make you more emotional. I don't know how much it affects the dopamine system as a whole, I never focused on it much individually.

I always think Uridine is much different than any choline-related supplement, even Citicoline which consists to a lesser part of it... I always find it's good for resetting a system (taken sublingually, not through the gut - although in your case that could be good). And it's more dopaminergc and GABA-ergic than a acetylcholine booster.

 

Wikipedia lists Beta-blockers, as I would have guessed, among others for Postural Orthostatic Tachycardia Syndrome.

 

In your former thread you say how you reacted well to Ashwaghanda. I think its strongest effect is serotonin receptors, downregulating 5HT1a autoreceptors and thus upregulating available serotonin. I would look into that more than whatever it does to acetylcholine, it can't be that strong compared to its famous serotonin-action. Aside from that, it acts similar to the likes of Astragalus, or rather Rhodiola, which is an adaptogen like Ashwaghanda. Adaptogen, in a common sense, seems to be a title for things that act on the cortisol- or stress-response system, or HPA-axis. Next to Ashwaghandha, usually Rhodiola and Schisandra are included. Have you given Rhodiola a shot?

You mentioned also Chamomile temporarily reversed previous insensitivity. Have you tried it again? It seems to be a strong Kappa-opioid antagonist, among other things, upregulated Kappa-receptors can make one feel bad, so I would usually recommend taking Chamomile occasionally.


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#4 dk2011

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Posted 28 March 2020 - 11:27 PM

@DaveX, could it be something with my immune system? I’ve heard there are theories about the immune system and acetylcholine being involved. Do you think it’s possible that by taking Acetylcholine precursors that would explain why it caused fatigue and my sensitivities to go away? And if so, how would I reverse this? When I tried Benadryl (Diphenhydramine) to see if it reversed it, it made my entire body feel like hell though, nerve pain all over, even though it’s supposed to be anticholinergic. When I was a teenager, I did used to take Allegra daily for several years.

#5 DaveX

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Posted 30 March 2020 - 04:23 PM

I've heard about acetylcholine being involved in the parasympathetic nervous system, which is involved in the immune system and many of the issues you have. I have no idea if taking acetylcholine precursors could make anything worse, normally it should just help the parasympathetic nervous system.

I don't see why acetylcholine would cause chronic fatigue syndrome. The assumption behind this seems to be that acetylcholine is so dominant that it inactives dopamine function and makes you unmotivated, but generally acetylcholine should make you more nervous, not tired, and it just seems a far fetch that this is the reason behind your fatigue. If it just causes exhaustion over time, you should still have too much nervous energy at other times.

It is common for diphenhydamine to make one feel bad, it has various effects, but I have no idea if it has anything to do with your issues. Since you say you have nerve pain, you can try things which are commonly taken for that, like Curcumin extract (high in Curcuminoids) or Capsaicin (from chili peppers).

Since you say you have Mast Cell Activation Syndrome, your immune system and inflammatory actions would definitely be involved.

Take a look here, for example:

https://selfhacked.c...antihistamines/

https://selfhacked.c...ne-intolerance/

Or here: https://selfhacked.c...e-th2-dominant/

https://selfhack.com...-immune-system/

 

I would also mention again Omega 3, as it also a mast cell stabilizer and anti-inflammatory.


Edited by DaveX, 30 March 2020 - 04:27 PM.

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#6 Keizo

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Posted 31 March 2020 - 06:22 PM

I've in the past had weird things going on with my autonomic nervous system. Like for example taking a hot bath and getting extreme tingling and discomfort, or having 115 BPM resting HR in the morning when taking 1.25mg dexamphetamine (1/4 tablet) the previous day (about 100 BPM without any) or being unable to drink coffee. Happened more or less after discontinuing benzodiazepine use, and persisted for quite some time.

 

I also associate being "choline dominant" with anxiety and muscle tension, for example. And reacting with e.g. headaches and tension when taking cholinergic supplements/drugs. I would say I always was and I can hardly imagine taking e.g. most of the racetams that people seem to enjoy, seems like madness to me because I tend to get headaches and brain fog rather quickly from most of them (fasoracetam excluded, that one I can take for weeks). Altho I'm not sure how useful this way of looking at it is. The only choline supplement I really tried was CDP-choline, it was weird and I did not enjoy it, too much tension. 

 

The one thing that seemed to work for me in many ways Cerebrolysin, it seemed to balance things out rather well, made me have less weird anxiety, fatigue, tension and problems with thinking (most of my problems were seemingly related to quitting benzodiazepines and included more severe things like trouble speaking which also was alleviated), but it either made me more sensitive to e.g. coffee or left it at a high sensitivity --- might just be the bensodiazepine use that was the main culprit in sensitivity, at least the bad kind. (Nowadays I occasional use some cerebrolysin just for the anti-depressant effect, and I think it does temporarily and for a bit of time increase sensitivity a lot to stimulants.) So I did have the combination of being tired and tense, for quite some time years back. (To my knowledge cerebrolysin mainly acts as various neurotrophic factors e.g. CNTF, NGF. But also I believe it might have some modest GABA receptor activity, and some other mechanisms relating to anxiety alleviation.) There's an oral version (should be at least decently similar in effect, altho I imagine a lot of the effects are left-out) called N-pep-12, goes under the name memoprove and maybe other names.

 

I wouldn't recommend looking to simple things like choline precursor, or dopamine precursor or whatever, other than maybe self-diagnostic tool. I've also had effects from tyrosine and low dose dexamphetamine where I got extremely tired and relaxed (mostly the dexamphetamine, and mostly first few days), like muscle tension in particular got alleviated at some point where I had the most problems after having had quit benzos for however many months, even tho it wasn't completely relaxing (like the amphetamine still  had crazy stimulating effects on my heart). I've never in my life felt so relaxed as wtih 2.5 - 5mg dexamphetamine. I actually used it as sleep aid for about 1 week (and yes it definitely was d-amphetamine as I now (years later) have a long-term prescription for it and have been taking it more regularly) before it turned around and gave more typical effects that people associate with the drug. Those reactions might have a lot to do with the specific substances too, tiredness from low level dopamine stimulation isn't unheard of.

 

And yeah a lot of anti-cholinergic (1st gen) antihistamines do weird things so I wouldn't draw too many conclusions from those. And also just taking an anti-cholinergic might not make you feel any better, even if it was as simple as finding some balance between neurotransmitters you might still overshoot in one particular area of its effect and feel bad as a result.

 

I've not tried Ashwaganda but it's one of the few herbs I'm interested in, it seems sort of like it could have some very good "balancing out" effects, but I mainly used to be interested because of alleged effects on NGF etc. Rhodiola is one thing I have tried (in combination with russian ginseng and schizandra) that was a really good blend of mild-moderate overall energy increase that I could tolerate back then (unlike coffee, or regular ginseng or just about anything). Along those lines of mild stimulating things that I think most people would tolerate I would add Fulvic acid (in particular the pure form which in the us can be found in wujinsan -- -either way fulciv acid might have some interesting effects on immune system and all kinds of things, it seems healthy to me, very low-key type of energy increase). I'm all for people taking supplements in attempts to improve health or well-being, however I have extremely low expectations, and if I had a chronic fatigue syndrome (or ADHD) diagnosis I'd seriously consider stimulant treatment or modafinil etc via medical doctor.


Edited by Keizo, 31 March 2020 - 06:23 PM.

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#7 DaveX

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Posted 04 April 2020 - 07:17 AM

Adaptogens decrease cortisol, which can make one feel good, or it is actually supposed to create a rebound effect after taking them (some of this stuff I never find completely transparent). However there are also some which simply increase cortisol, and so would make you feel more awake, like Shatavari. It tends to be cheap as a powder and I find it among the most harmless stuff to give a try.
You can have Rhodiola on hand if this isn't for you.

And just for diagnostic purposes, I would consider (if you haven't already done so) taking some mild cholinergic supplement again, like pure choline instead of a nootropic or herb, just to see if it is the main culprit. Since your experience with diphenhydramine at least seems to indicate that your main issue is not too much acetylcholine.

I am personally also currently having good experiences with Palmitoylethanolamide (PEA) which is a strong anti-inflammatory and widely used in veterinary medicine (because they are not so big on special medicine) but also known to have positive effects in humans. It feels a bit dopaminergic also, and I would compare it to Astragalus to some extent, although it is more pure in a specific direction, whereas Astragalus has mixed effects. It is an PPAR alpha agonist, for one, which I chose it for, as there were some studies speaking about effects associated with that receptor...

Edited by DaveX, 04 April 2020 - 07:35 AM.


#8 Keizo

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Posted 04 April 2020 - 08:37 AM

Yea neurotransmitter theory (or how it used to be) seem to get a bit weird and simplistic anyway. But if someone really wants to try and delve into it and suggestions for herbs etc based on dominant/deficient neurotransmitter activity, there's this book by Braverman called Edge Effect. I didn't find it that useful, but then I never bothered trying some of his suggestions. But it does cover a lot of knowledge about the human that I assume still is more or less accurate.

 

In my case I think I had 1. dysfunctional GABA receptors (downregulated due benzo use) and/or 2. as a result of 1 had created dysfunction in some other system further downstream even tho the GABA might've been restored. Very possibly cortisol or broader hormone systems implicated, because I had e.g. testicular growth 2 years after I quit benzos and started eating properly etc (don't think it's normal to have +100% (from 12-15ml to 25-30ml each)  testicular volume increase at age 23 within a few months, even if I had some vitamin D deficiency and borderline low BMI prior.

Speaking of PPAR resveratrol does something there https://www.ncbi.nlm...les/PMC4212005/ https://www.scienced...211383517301624 , at this period of testicular growth I took trans-resveratrol (500mg or less/d) for those few months (maybe it kickstarted/reset my hormonal system due aromatase inhibition or SERM effect).

 

Astragalus is really interesting. I've only used cycloastragenol (one compound found in the plant) years ago, it definitely produces a noticeable effect. For me it made me tired right after taking it (if I took let's say 50mg 98% cycloastragenol or more) and at the same time rather energetic in the weirdest way. I consider that a health supplement if anything, rather than anything I'd purchase for subjective effects. If I recall the other variations on the herb/extract might be rather different in their usefulness. 


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#9 DaveX

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Posted 07 April 2020 - 09:16 PM

Re: My comments about Shatavari and raising cortisol. I'm not really sure how Shatavari works, I only read once that it raises cortisol and it feels a bit contrary to things which are said to lower it, even while having quite positive effects. However it only feels good for about 2 hours (half an hour or so after taking it), then it starts getting worse and can feel kind of uncomfortable, as it also does at higher doses. I don't know if the early or later effects are due to cortisol, or any of them, but it seems to have more complex effecs than I thought.

Edited by DaveX, 07 April 2020 - 09:18 PM.


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