37 replies to this topic

[Ukko]

It is interesting how many people believe simplistically that brain acetylcholine levels are the sole key to higher IQ and better memory. I have had to learn the hard way that such is not the case. Excess ACH only gives me brain fog, anxiety, confusion and poorer memoery. Never saw much scientific support for that before the below study, admittedly with mice. Most of us know that excessive acetylcholine causes depression and/or anxiety, right?

http://brainupdates....ation-overload/

Now, folks take it easy with stacking things like acetylcholine esterase inhibitors, eggs, lecithin, DMEA, ALCAR and various esoteric forms of choline with each other. May make you dumber, as you may lose that key thing called insight and wisdom enabling you to differentiate between the noise and the signal, the relevant and the less relevant. But you might make a hell of an athlete, it seems. I guess this supports the view that being simple and having less insight is conducive to being a really good athlete. Totally believable Maybe the sanest approach indeed is to rely on ACH receptor sensitizers like Noopept. Maybe racetams work by depleting excess ACH...

Edited by Ukko, 26 June 2013 - 05:42 AM.

[brainslugged]

The interesting thing about this is that the symptoms of "had terrible attention spans, as well as dysfunction in working memory and spatial memory" are also result of low dopamine.

ACh is known to have an inverse relationship with dopamine in certain aspects. Anticholinergics were, at one time, used to treat Parkinson's, but the side effects were very bad.

This raises the question, what if cholinergics are combined with dopaminergics.

Theoretically, the problems of each are counterbalanced, although in reality there are bound to be some side effects. My bet would be that it would be severely anxiogenic, but I wonder how high the dose would have to be before the anxiety outweighed the increase in cognition, and if the anxiety could be reduced by a drug acting by a 2ndary mechanism, thus inhibiting the anxiety without inhibiting the cognitive effects.



This is also very, very interesting for another reason. The cholinergic increase decreases fatigue. Maybe this answers why sulbutiamine is useful in chronic fatigue (because it is cholinergic, and NOT because it sensitizes D1).

Edited by brainslugged, 26 June 2013 - 06:11 AM.

[lammas2]

I have asked this question many times, but never found a reasonable answer - how do you lower excess acetylcholine (assuming that your baseline ACH is "high")?

[Tom_]

No Ach doesn't lower 'IQ' it induces some depressive symptoms (problems assimilating and conentration) and with chronic raised levels it will tank serotonin (and by extention melatonin - causing insomnia), raise noradrenaline causing anxiety, hypervigulance and lower dopamine causing decreased hedonic tone. Obviously you are unlikely to have a gross increase in Ach across the entire brain in a mental illness and this is why supplements are less likely to cause all of these effects. The decrease in those types of neurons firing will only be in certain pathways that are effected by Ach ex: Mesolimbic and Mesocortical pathways (pleasure, motivation etc) which have very little to do with memory and learning functions per se (although they provide the motivation the excitation to other areas). These symptoms aren't the result of 'low dopamine' - which has very little directly to do with learning.

The only half reasonable way I can think of to lower Ach is TCA therapy.

[Ukko]

Tom, and what might your take on the linked study be? That it was done on mice and, hence, is of no relevance?

[jly1986]

In my experience, taking too much centrophenoxine as a choline source does cause depression for me. But at the same time, it seems to enhance my cognition, rather than dull it. I'm considering taking phenylalanine and/or tyrosine on the advice of another member here to help boost dopamine to hopefully counter the depression, but haven't tried it yet.

[Tom_]

No study with mice is completely extrapolatable to humans, conversley most of the findings in the study are reasonably consistant with what I said (bare in mind what I'm talking about is limited to a few areas within the brain (where there are high densities of certain nicotinic receptors and m1 + m5 receptors).

This is one of the most interesting reads I've ever had the pleasure of and changed or at least added a great deal to my view of mood disorders.

http://www.acnp.org/...1000095/CH.html

jly, you may find adding in a racetam that has been shown to burn though Ach (piracatam for example) will help with your dsyphoria - althought this is purely theoretical. On the other hand DLPA (phenylalanine) has been shown to act as an antidepressant and for cognitive enhancement I would always recommend a dopamine AND noradrenaline supplement (everyone always forgets about noradrenaline which is equally important). DLPA fits the bill perfectly. You may find adding in vitamins & minerals that help with the metabolism related to neurotransmitters and general neuron functioning (calisum, vit B and c), omega 3 etc... will also help a great deal. If the dsyphoria lasts after you have slept I would advise you to also add in a serotonergic precuser. 5HTP imo is not your best option and 1-5 grams of L-tryptophan will serve you better.

[John Schlongfellow]

I'm currently testing l dopa to improve mood along with cholinergics pramiracetam, lecithin and 6 eggs a day , DMAE starting next week.
didn't plan it that way bit here is this thread !

I'm also prone to depressive episodes where I feel like I'm walking underwater. No mistaking that.

For the sake of science, and because I've learned so much here, I'll try and dose myself into hypercholinergic state.
what dose?
how do I get out? yes I see the post above mine. Plan B?

Edited by John Schlongfellow, 26 June 2013 - 11:52 PM.

[Tom_]

There is a good chance you are already in a hypercholinergic state. Uping that further could cause much more serious adverse effects, not limited to heart arythmias, acute psychosis, neurotoxity, sezuires, suicidal or severe depressive reactions....science isn't worth it. Plus my link gives all the research you need. Hundreds of people and animals involved in studies.

I have to say mate, your stack is utterly awful. Its not safe (I'm concerned with the exessive cholinergics and the L-dopa), its not going to be long term effective, its not going to anywhere near as effective as stacks you could try....

Sorry to be a kill joy

[John Schlongfellow]

Your link is very good, assuming it's all valid.

that wasn't meant to be a stack

Most of my time is spent hypomanic with occasional mega depressive swings.
l dopa is one tool in the bag, just reading the anhedonia thread now

lecithin was totally unrelated, but safe to say it had the intended effect

pram and company were aimed at ADD and increasing lucidity and short term memory so I might start bailing water earlier in the onset of depression, also to attempt better impulse control as doing stupid things can be depressing.

eggs are a source of protein, guess you can add half a chicken and several jalapeneos to my "stack" eh?

FWIW, the word mate conjures a certain image for most of the English speaking world.

Your apprehesions concerning my current experiments are noted. Thanks for the concern.
I'd add CILTEP + caffeine + 5mg adderal in there since we are talking about stacks.
just some of a long list I'm working through slowly to guage effects.
sort of a "Golly what does this button do?" approach

everyone who has been through the antidepressant wringer knows the doctors are doing exactly the same thing
" Uh... yeah well we'll hold this button down for six months and see what happens."

Edited by John Schlongfellow, 27 June 2013 - 01:13 AM.

[Tom_]

If you carry a diagnosis of Bi-polar there is good evidence (although in no great quantity) that if you can control your Ach and noradrenaline then you can remain in a euthymic state. The evidence for cognitive dsyfunction even in eythmic states in Bi-polar is incontrivertable and impusivity is a hallmark of Bi-polar. I'm no longer sure if ADHD and Bi-polar should be diagnosed together, where once I saw them as comorbidites. You may well find if you can control the Bi-polar the ADHD like symptoms will be signifcantly reduced or even go completely. On the other hand more chronic hypomanic type symptoms with brief dsymias could be misdiagnosed as Bi-polar where it is in fact ADHD. This is of course assmuming you are talking about seriously pathological symptoms rather than as a way of expressing your behaviours.

Sorry about the stack assuption. There is a fairly large thread of the dangers of L-dopa (normaly on page 1 or 2) and wikipedia is a good scare read for it. If you do have Bi-polar it could push you into fast cycling or simply swap you to the other extreme. Its also a bitch for causing worse impusivity.

Lecine, eggs and DMEA are all sources for choline.

Is it a good image or a bad one? I'm going wiith bad? Or is it just the image of an aussie in the outback or an Londoner with gruff accent and a bald head?

[John Schlongfellow]

That certainly is the question isn't it?
either, or, comorbidity ?
a GP diagnosing ADD in a 5yo and dispensing obscene amounts of ritalin leading to some dysfunction in the dopamine system?

I'm here as a self educated adult who's scarce been helped by years of this med or that and feels he could hardly do worse.
Lord knows I'm smarter than most I meet, yet cant maintain long enough to utilize it.
Might as well be a savant.

thanks for the reply, and sorry to make the thread about me
I find it better to speak of what I know.

from your link
THERAPEUTIC IMPLICATIONS

Applications of the adrenergic-cholinergic balance hypothesis to the treatment of affective disorders has been sporadically attempted over the past several decades. As described above, anticholinergic drugs may or may not have antidepressant efficacy. Cholinomimetic treatment of mania has been more consistently rewarding. The choline precursor lecithin was used by Cohen and colleagues in the early 1980’s to treat mania, with promising results. Stoll et al (116) demonstrated that choline augmentation of lithium therapy in six rapidly cycling Bipolar Disorder patients caused a substantial reduction in manic symptoms in five, and a marked reduction of all symptoms in four. Similarly, Leiva (62) reported efficacy for phosphatidal choline in the treatment of mania.

mania or hypomania is frequently related to my lapses in judgement

currently low dosing lithium carbonate over the last 2 weeks, 25mg daily, have orotate on the way
going to look into that study I quoted

Edited by John Schlongfellow, 27 June 2013 - 01:58 AM.

[Tom_]

If this was me I would get on lithium (not that orotate crap with no evidence) or valporic acid under a psychiatrist and once you have stabilized on it introduce a choline source.

I'll make a proper response (if I remember) tomorrow, its 3am here.

Edited by Tom_, 27 June 2013 - 01:51 AM.

[John Schlongfellow]

Thanks in advance for the proper response ;-p

The lithium carbonate is leftover from my adventures in lithium, courtesy of one of the aforementioned button crazy doctors.
Supervised and everything over a 12+ month period.
efficacy was less than stellar

hey Tom , I just noticed a post of yours in a add/ocd/etc thread.
I'm gonna work up a list of answers to the string of questions AND stop hijacking this thread.

Edited by John Schlongfellow, 27 June 2013 - 02:38 AM.

[Ukko]

Thanks in advance for the proper response ;-p

The lithium carbonate is leftover from my adventures in lithium, courtesy of one of the aforementioned button crazy doctors.
Supervised and everything over a 12+ month period.
efficacy was less than stellar

hey Tom , I just noticed a post of yours in a add/ocd/etc thread.
I'm gonna work up a list of answers to the string of questions AND stop hijacking this thread.

Hey, that discussion was interesting for use others. It does seem to me that a huge amount of folks with good intentions seeking to boost ACH and/or to block ACHe to give them superhuman nootropic brain power. And, yet, they end up with depression, anxiety and ADHD type issues. What an irony.

[John Schlongfellow]

well noots led me here so maybe I'll have found my answers, albeit via the scenic route.

I already had depression, pre-noots.

I said that about hijacking the thread since I found the mental health section with multiple threads I have to read to get up to speed.
I hate the newb mantra of duplicate questions/threads as much as anyone.
sure everyone has to start somewhere, shame the default position is frequently pure lazyness. (spoon feed me please)

Edited by John Schlongfellow, 27 June 2013 - 06:49 AM.

[KoolK3n]

This raises the question, what if cholinergics are combined with dopaminergics.

http://www.ncbi.nlm....pubmed/22595038. nAChA7Rs?

[Ukko]

I have asked this question many times, but never found a reasonable answer - how do you lower excess acetylcholine (assuming that your baseline ACH is "high")?

 

Lammas, try DMAE. Taitaa olla laitonta Suomessa. Works wonders for me to reduce ACh. It is a false cholinesource used to induce ACh depletion in research. Dozens of studies on that. Massive clarity and energy.

[lammas2]

I have asked this question many times, but never found a reasonable answer - how do you lower excess acetylcholine (assuming that your baseline ACH is "high")?

Lammas, try DMAE. Taitaa olla laitonta Suomessa. Works wonders for me to reduce ACh. It is a false cholinesource used to induce ACh depletion in research. Dozens of studies on that. Massive clarity and energy.

Do you think centrophenoxine will work as well (I have access to that)? Considering it is DMAE+pCPA http://en.wikipedia....i/Meclofenoxate
Could you provide some links about DMAE depleting ACh or explain how is it doing that?

Also, forskolin upregulates AChE expression, so more ACh gets broken down.
http://www.longecity...620#entry596755

Edited by lammas2, 30 June 2013 - 07:19 AM.

[lammas2]

http://www.longecity...iracetam-mania/
According to this topic, piracetam (without a choline source) is definately worth a try, as it successfully lowers ACh.
(If anyone knows an European source for piracetam, please PM me)

[BLimitless]

I can correlate with the acetylcholine overload. When I stack AChE inhibitors things get very messy. I lose my memory and get very ditzy, scatter brained.


One time I mixed harmala alkaloids with Noopept and ended up going round and round a certain area I knew very well, trying to find the place I was getting to on the map except... I lost all sense of spacial awareness. I would be standing in the exact street on the map and could not work out what was what, which direction went where. It was bizarre. Normally I experience the polar opposite, I can normally get from A to B in my sleep without a hitch like everyone else esp. when zoned out as many a night out during the weekend always calls for!



Some things are just not meant to be mixed!

I found that I could derive more cholinergic benefits from dosing niacin/niacinamide in conjunction with whatever. It seems to hit the nootropic spot much better than overloading the choline system altogether which often has very messy effects.

Edited by BLimitless, 03 July 2013 - 10:57 PM.

[Ukko]

I have asked this question many times, but never found a reasonable answer - how do you lower excess acetylcholine (assuming that your baseline ACH is "high")?

Lammas, try DMAE. Taitaa olla laitonta Suomessa. Works wonders for me to reduce ACh. It is a false cholinesource used to induce ACh depletion in research. Dozens of studies on that. Massive clarity and energy.

Do you think centrophenoxine will work as well (I have access to that)? Considering it is DMAE+pCPA http://en.wikipedia....i/Meclofenoxate
Could you provide some links about DMAE depleting ACh or explain how is it doing that?

Also, forskolin upregulates AChE expression, so more ACh gets broken down.
http://www.longecity...620#entry596755

Lots of studies you can easily find. Do Medline queries with deanol, false, acetylcholine, precursor etc. as search words. One study here. As to what Centro does? Beats me. Likely would lower ACHe while suppressing choline intake to brain due to being metabolized into DMAE. What that does overall...no idea.

http://www.ncbi.nlm....v/pubmed/727735

[Joe Cohen]

Taking too much AChEI f*cked me up. A little is good, a lot is terrible. I witnessed the same effects as the mice in the brainupdates link. I then did research on every compound that I take thas AChEI properties. It's more than you think....I didn't link out to all of them, but just google.


AChE(-): Tulsi, Amla(conflicting), Rehmannia, Berberine, Epimedium, Licorice, Tea/EGCG, Curcumin, Bacopa, Ashwagandha, Caffeine, Melatonin?, Ginger(conflicting), Fenugreek, Blueberries, GSE, Gotu Kola(conflicting), Cinnamon, Reishi, Danshen, Zinc, Saffron, Ginseng, Propolis, FO
(Copper, Gallic acid, Quercetin, Insulin?, Andrographis(weak), Schisandra, Celastrus, Ginkgo, Lemon balm, Sage, Rosemary, Noni, Hup-A, Shatavari, THC, Coumarins(Cinnamon, Chamomile, strawberries, cherries), Jatamansi, Fo-ti),

[chung_pao]

An excess of any one neurotransmitter makes you dumb...
The orchestration of Intelligence is very complex, and relies on more than one neurotransmitter...

High-dosing on any one precursor to neurotransmitters in the morning, on an empty stomach, will definitely mess up the majority of your day.
(5-htp/tryptophan, tyrosine, choline... maybe not glutamine though...)

Edited by chung_pao, 10 July 2013 - 08:30 PM.

[RJ100]

Wow, so glad I found this thread.

 

Like Joe, I've been unwittingly adding acetlycholinesterase inhibitors to my regimen over the last year and ended up putting myself in an acetylcholine-fueled brain fog with mild depressive feelings.

 

Lots of eggs - choline source

lots of berries - inhibits AChE

cinnamon - inhibits AChE

triphala - inhibits AChE

melatonin - inhibits AChE

etc..

 

I still believe some inhibiting of acetlycholinesterase is a good thing, so the question becomes what gets cut, by how much, do I cycle?

[Flex]

Edit

Edited by Flex, 13 October 2014 - 04:34 PM.

[JellyRev]

cdp choline as the sole choline source makes me depressed. 

 

Alpha GPC+ALCAR on the other hand makes me sharper than ever. and it nullifies a lightheaded, foggy, fatigued feeling I get from the first cigarette I inhale when I do smoke. 

[Godof Smallthings]

What dose size of alpha gpc + alcar?

[JellyRev]

600-900mg alpha gpc+ 300-500mg Alcar. 

 

Another interesting thing I've noticed is combining 900mg of alpha gpc with 2g of taurine and 2 excedrin pills will wipe out a hangover and restore cognition back to normal within 20 minutes. 

 

[RJ100]

Does anyone have experience cycling or rotating AChE inhibitors? Taking them all in a stack just isn't working for me.

 

I'm thinking maybe curcumin for a week, followed by quercetin, then bacopa, etc.