Acetylcholine and Mood
Orajel 09 Mar 2012
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)
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).
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)
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.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.
In regards to depression: (source 1)
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).
Also: (source 1)
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.
Source 2
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.
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.
MrHappy 10 Mar 2012
That being said, both alpha-GPC and CDP choline will increase dopamine levels, which could counterbalance the issue.
khemix 10 Mar 2012
Really? I never heard that either of these increase dopamine. Do you have a source?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.
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.
MrHappy 10 Mar 2012
http://www.longecity...ptor-densities/
CDP-choline breaks down into choline + uridine. Uridine modulates dopamine release and increases receptor density.
Orajel 11 Mar 2012
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.
the_newsoul 12 Mar 2012
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!
gamesguru 12 Mar 2012
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.
the_newsoul 14 Mar 2012
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.
gamesguru 14 Mar 2012
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.
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.
the_newsoul 15 Mar 2012
IMO brain fog should be related to low levels of dopamine, but dont really see the relationship with an excess of choline
the_newsoul 15 Mar 2012
Translated. Source: http://members.fortu.../neurotrans.htm
Interesting!
Edited by the_newsoul, 15 March 2012 - 12:33 AM.
Reformed-Redan 15 Mar 2012
Orajel 15 Mar 2012
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.
the_newsoul 15 Mar 2012
Orajel 15 Mar 2012
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.Orajel, could you describe better how you felt on higher doses of choline and Piracetam? Brain fog? Mood?
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.
DonTolentine 15 Mar 2012
flag 03 Oct 2018
I have every symptom of acetylcholine excess.
I am not too interested is tweaking my neurotransmitters but would
like to simply have a lifestyle that would balance them.
Is there an answer that doesn't involve a by the seat of your pants
dose balancing act?
although I am very tempted to experiment I must admit. lol
jack black 04 Oct 2018
some people take piracetam to lower ACh, not sure how that works. and stay away from any sources of choline! including fish oil and most "brain" supplements.