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Acetylcholine and Mood

acetylcholine

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#1 Orajel

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Posted 09 March 2012 - 11:07 PM


Acetylcholine is a neurotransmitter with a wide range of applications within the central and peripheral nervous systems. This neurotransmitter acts on both muscarinic and nicotinic receptors. For the purposes of this thread, I'm going to focus on its applications within the brain, and specifically, its application on muscarinic receptors.
Many of us seek to boost our natural acetylcholine levels because acetylcholine is linked to attention, focus and memory. For example, Alzheimer’s patients have decreased levels of acetylcholine in their brains. This is why many Alzheimer’s treatments seek to increase acetylcholine levels, usually through acetylcholinesterase inhibition.

Many of us who experiment with nootropics also seek to boost our acetylcholine levels. We can do this through a variety of mechanisms, usually with acetylcholinesterase inhibitors, acetylcholine precursors, and substances that mimic acetylcholine (nicotine, acetylcarnetine). Evidence supports the theory that increasing acetylcholine levels can subsequently boost ones' learning capacity.

However, there are other implications that come with increased levels of acetylcholine. Primarily, I'm going to focus on mood-related implications. Some evidence supports the idea that depression is related to higher levels of acetylcholine!

Here are the links to the 2 sources I'm referencing: I apologize, I would find more sources for this info if I had more time. Interesting information nonetheless.
1) http://www.acnp.org/...1000095/CH.html
2) http://www.psychosom.../3/248.full.pdf


In regards to behavioral inhibition (source 1)
[quote]Significantly, increasing central cholinergic tone with such centrally active cholinomimetic agents as physostigmine, arecoline, and oxotremorine usually induces or enhances the behavioral analogs of depression in such models of depression. Thus, centrally acting cholinomimetic drugs consistently produce behavioral inhibitory effects including lethargy and hypoactivity, activation of the HPA axis, decreases in self-stimulation (43, 54, 55), increases in behavioral despair in the forced swim test, and decreases in saccharin preference (88).[/quote]

It appears that cholinesterase inhibitors can decrease manic symptoms in manic-depressive humans, which supports the theory that increasing acetylcholine can decrease positive mood. (source 1)
[quote]Several studies have shown that centrally active cholinergic agonists and cholinesterase inhibitors possess ant-manic properties. In a seminal study by Rowntree et al. (100), the centrally active cholinesterase inhibitor DFP was given to manic–depressive patients and normals. The normal subjects and remitted manic–depressives developed irritability, lassitude, depression, apathy, and slowness and/or poverty of thoughts.[/quote]
However, there appears to be a link only between centrally acting cholinesterase inhibitors on reducing episodes of mania. Non-centrally acting cholinesterase did not exert the same effect.


In regards to depression: (source 1)
[quote]In addition to observations of depression-induction caused by DFP (100) and cholinomimetic insecticides (34), Janowsky et al. found induction and/or intensification of depressive symptoms in actively ill bipolar manic patients given physostigmine, as well as a worsening of depression in groups of unipolar depressed and schizoaffective depressed patients (45).[/quote]

Also: (source 1)
[quote]Depressed moods have also been observed in subjects receiving acetylcholine precursors, including deanol, choline, and lecithin. Davis et al. (18) and Tamminga et al. (117) found that depressive symptoms occurred in some schizophrenic patients who were treated with choline, a phenomenon that was atropine-reversible. In a subgroup of cases, it was noted that depressed mood was a side effect of choline and lecithin treatments employed to try to reverse the memory deficits of Alzheimer's Disease (117). Also, Casey (9) observed that a depressed mood and, in some cases, a paradoxical hypomania occurred in some deanol-treated tardive dyskinesia and other movement-disorder patients. Thus, precursors of acetylcholine may induce a depressed mood, a finding that is consistent with the adrenergic-cholinergic imbalance hypothesis.[/quote]

Source 2
[quote]The results indicate that virtually all
patients receiving physostigmine exhibit
symptoms consistent with a state of psychomotor
retardation. In addition, most
patients with an affective component to
their symptoms exhibit increased depressed
mood following physostigmine
administration.[/quote]


The second document I read describes a link between a number of cholinesterase inhibitors and depressed mood. DFP (an insecticide) is cited in both documents, as well as physostigmine, among several others. I doubt if any of us will be taking these, but the point is that all of these compounds increase levels of acetylcholine. It has also been reported that acetylcholine precursors can induce depressed mood. In addition to this, compounds that decrease acetylcholine are associated with increased mood (buproprion, diproxymine). I’m not suggesting this is proof, or that this is a scientifically substantial post I’ve made here, but its interesting information to consider (especially if you're an avid self-medicator like myself!). I’m by no means saying that acetylcholine causes depression, but it could play a role.

Also, see the “Evidence that Acetylcholine May Cause Depression” chart on page 255 of source 2.

That being said, we all need acetylcholine, and being happy aint’ everything! But being smart isn’t either.

Edited by Orajel, 09 March 2012 - 11:47 PM.

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#2 MrHappy

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Posted 10 March 2012 - 01:14 AM

Yes - it's antidopaminergic, hence depression potential.

That being said, both alpha-GPC and CDP choline will increase dopamine levels, which could counterbalance the issue.


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#3 khemix

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Posted 10 March 2012 - 04:56 AM

Yes - it's antidopaminergic, hence depression potential.

That being said, both alpha-GPC and CDP choline will increase dopamine levels, which could counterbalance the issue.

Really? I never heard that either of these increase dopamine. Do you have a source?




As for acetylcholine, I took galantamine 8mg once which was very strong and made me vomit. I remember reading that it helps calm a racey mind but personally never found this to be the case.

#4 MrHappy

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Posted 10 March 2012 - 08:35 AM

http://www.ncbi.nlm....pubmed/3709792/

http://www.longecity...ptor-densities/

CDP-choline breaks down into choline + uridine. Uridine modulates dopamine release and increases receptor density.



#5 Orajel

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Posted 11 March 2012 - 08:04 AM

consider that dopamine by itself won't do any more for mood than acetylcholine alone does for memory. Also consider that an over-responsive dopamine-reward system is associated with sociopathic tendencies

Also keep in mind that the whole point of the first article is to demonstrate central muscarinic mechanisms are associated with depression, and this doesn't nessicarily have anything to do with dopamine.

Edited by Orajel, 11 March 2012 - 08:08 AM.


#6 MrHappy

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Posted 11 March 2012 - 11:14 AM

Granted, but it's not the whole picture. :)



#7 the_newsoul

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Posted 12 March 2012 - 01:06 PM

Yes - it's antidopaminergic, hence depression potential.

That being said, both alpha-GPC and CDP choline will increase dopamine levels, which could counterbalance the issue.


Very interesting post!

MrHappy, how come Aniracetam usually works for people with ADHD if it has cholinergic effects? If it was also antidopaminergic, I guess the efects should not be good at all.

That said, I have been mixing for about 2 weeks ALCAR + Aniracetam + Methylphenidate and the mix does not work well for me (less motivation, more brain fog)...

For me, MPH alone is fantastic. Aniracetam & ALCAR alone is just ok. I have ADHD.

Thanx!

#8 gamesguru

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Posted 12 March 2012 - 03:59 PM

We (some of us) think acetylcholine and dopamine are antagonists, but we have little proof. For this reason, I only intake very conservative doses of choline, rarely exceeding 100 mg daily of mixed forms. I like citrate, bitartrate, CDP, and GPC.

I was very interested to hear someone claim that certain forms of choline will stimulate a dopamine production. I would not discredit this claim based on the testimony of ADHD patients who say choline hurts whereas amphetamine helps. It could be that the dopamine production is at a different part of the brain, and we must also remember that choline, unlike amphetamine, won't inhibit VMAT2, nor will it reverse DAT, nor will it act as an MAOI, nor will it act on tyrosine hydroxylase. All that said, we shouldn't be comparing the dopaminergic action of choline precursors to that of amphetamines.

#9 the_newsoul

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Posted 14 March 2012 - 11:24 AM

dasheenster, I have ADHD and after my short experience after about 8 months is that methylphenidate has helped me a lot. I tryied aniracetam and ALCAR combined with MPH for about 3 weeks and at the end it the effect was starting to be bad: less motivation, brain fog, and my mood was usually good at the begining of the day and bad at night.

I also tryied aniracetam & MPH without alcar and it was not so bad, but i still had brain fog and kind of a weird feeling.

It may be that I dont react well to choline or that choline was messing my dopamine levels as you say. I really dunno.

I may try in a couple months ago with a smaller quantity of aniraceram.

#10 gamesguru

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Posted 14 March 2012 - 11:59 AM

Always, when cholinergics seem to cause or exacerbate depression, drop the dosages. It's insanity to use the same dose and to expect a totally different effect. Some years ago when I was just a novice, I would take over 2g of alpha GPC daily, in accordance with many recommendations on this forum. It took me an extremely long time (almost a year?) to realize it was the greater cause of my brain fog. I believe it was also depleting my brain cholesterol which manifested itself as fatigue, frustration, and amotivation. Classic burnout symptoms.

Aniracetam seems to me to induce the same sort of mindlessness as choline, presumably due to its (positive?) interaction with nAchRs. It has further been noted that nAchR antagonists may have therapeutic effects for depressive patients. All this suggests aniracetam has an evil side, and Chilo, one of the 7 ancient Greek sages, was right again: all things in moderation, nothing in excess. Of course, I could be leaning towards piracetam and away from aniracetam due to a purely subjective bias...after all, I made piracetam my favorite. I suppose I should follow my own advice, and give aniracetam another shot, but this time in a more moderate dose...but my stubbornness gets in the way.

' class='bbc_url' title='External link' rel='nofollow external'>http://www.nature.com/mp/journal/v7/n6/full/4001035a.html']Nicotinic acetylcholine receptors as targets for antidepressants

Abstract
While the monoamine deficiency hypothesis of depression is still most commonly used to explain the actions of antidepressant drugs, a growing body of evidence has accumulated that is not adequately explained by the hypothesis. This article draws attention to contributions from another apparently common pharmacological property of antidepressant medications¾the inhibition of nicotinic acetylcholine receptors (nAChR). Evidence is presented suggesting the hypercholinergic neurotransmission, which is associated with depressed mood states, may be mediated through excessive neuronal nicotinic receptor activation and that the therapeutic actions of many antidepressants may be, in part, mediated through inhibition of these receptors. In support of this hypothesis, preliminary evidence is presented suggesting that the potent, centrally acting nAChR antagonist, mecamylamine, which is devoid of monoamine reuptake inhibition, may reduce symptoms of depression and mood instability in patients with comorbid depression and bipolar disorder. If this hypothesis is supported by further preclinical and clinical research, nicotinic acetylcholine receptor antagonists may represent a novel class of therapeutic agents for treating mood disorders.

→ source (external link)


#11 the_newsoul

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Posted 15 March 2012 - 12:16 AM

very interesting again!! Why do you think choline could cause brain fog? or thats the effect it seems to does to me.

IMO brain fog should be related to low levels of dopamine, but dont really see the relationship with an excess of choline

#12 the_newsoul

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Posted 15 March 2012 - 12:28 AM

"In a normal brain, the levels of dopamine and acetylcholine, are in equilibrium and equal in their inhibitory and excitatory functions. When levels of dopamine decrease, this balance is broken because the acetylcholine is beginning to have an excess of excitatory activity, which causes Parkinson's disease. Dopamine is found in the pars compacta of the substantia nigra, and the reasons why the neurons die and cease to keep the system balanced on the striatum are ignored."

Translated. Source: http://members.fortu.../neurotrans.htm

Interesting!

Edited by the_newsoul, 15 March 2012 - 12:33 AM.


#13 redan

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Posted 15 March 2012 - 04:44 AM

Had 500g of Choline Bitartate. Threw it away. No need for going supercritical.

#14 Orajel

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Posted 15 March 2012 - 05:53 AM

Today, to test it out, I took a higher dose of piracetam and more choline than I normally do. I felt terrible. There's definately a correlation between too much acetylcholine (and acetylcholine related activity) and feeling down. From what I understand, piracetam increases the density of muscarinic receptor sites. I've been taking piracetam at high doses for the past 2 weeks, so it seems plausable that there could be something happening here. Needless to say I'm dropping my piraetam dose to around 9g a day.

Due to poor seller info, I was under the assumption that a teaspoon of piracetam contains about 2.1 grams of powder. This is most certainly not correct, one teaspoon of piracetam contains around 6.4 grams of powder.

#15 the_newsoul

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Posted 15 March 2012 - 12:54 PM

Orajel, could you describe better how you felt on higher doses of choline and Piracetam? Brain fog? Mood?

#16 Orajel

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Posted 15 March 2012 - 04:20 PM

Orajel, could you describe better how you felt on higher doses of choline and Piracetam? Brain fog? Mood?

Bran fog is difficult for me to assess because I have HPPD; when my vision is distorted, it's easy to assume I'm experiencing brain fog, which isn't alwasy the case. My vision was a bit foggy with the high doses of choline/piracetam, so there could have been some brain fog. I noticed my mood was low, I felt flat and felt that I was giving off a flat affect. I almost felt inhibitted, which can come with feeling low. Thinking more than I was talking, over analyzing things, not very talkative.

I'm concerned with piracetam increasing muscarinic receptor density, because muscarinic receptor agonization is implicated in the onset of depressive symptoms. I'm going to scale down my piracetam dose, take it for another month, and see how I feel. In the end, I may go with another racetam. Aniracetam has anti-anxiety effects, but I've heard it can make you foggy and be mildly sedative, not what I'm looking for.

I suffer from anxiety (social, panic attacks) and chronic fatigue syndrome, as well as past depression, so I may be more sensitive to these effects. I am NOT diagnosing myself here, these come from doctors. So I'm looking for something that will chill me out, while not being sedative or slowing myself down in any way. I'm sure you can see the paradox here. I'm pretty un-responsive to medication as well and CBT has helped, but not enough.

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#17 DonTolentine

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Posted 15 March 2012 - 06:36 PM

Everytime I use piracetam I feel more depressed. I see there is a correlation between high IQ and depression. The individuals with more IQ maybe have a increased cholinergic system. I know two very high IQ guys with exceptional memory, verbal and math skills that are suicidal and depressed. They are very amotivational and poor. One have doctorate in physics and another is a MD. They live in misery because they don't like to work. Both use marijuana to calm the mind. Maybe dopaminergic drugs are better! My hypothesis is that a very high IQ tends to low dopamine.
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