Cholinergic Dominance: Theory, Meaning, And More

[vc_row][vc_column][vc_column_text]uridine_circleNOTE: this post is strictly theoretical, and though I’m citing a few sources inside the post, a lot of this is just my contention based on years of experience.

Also: credit where credit’s due. The term choline dominant was coined by Steven Fowkes and popularized by Dave Asprey.

There’s a term being thrown around in the nootropics community that describes a state in which the user has created an acetylcholine dominant brain. A state where, through genetics or the use of cholinergics, a person has more circulating acetylcholine in their brains.

In this state, users report a variety of side effects, and they range from brain fog to anxiety. Here are some of the main symptoms of what’s been called cholinergic dominance:

  1. Tenseness in muscles, particularly in the neck and shoulders.
  2. Grinding of the teeth.
  3. A depressive effect on the brain (commonly seen with excess doses of Alpha GPC).
  4. A feeling of lethargy that doesn’t go away unless you sleep.
  5. Working memory deficits.
  6. Verbal fluency problems.

That isn’t to say that there aren’t more symptoms associated with cholinergic dominance, but those are some of the primary outcries from your brain, that you need to calm it down with the cholinergics.

Acute VS long term cholinergic dominance

Acute: In line with the rest of the above notions in this post being strictly theoretical, I also think there’s something to be said about acute VS accumulated cholinergic dominance. Simply, acute cholinergic dominance may result in you having some, all, or more of the above symptoms, for a short period of time, after you’ve taken a high dose (or a high dose for you) cholinergic compound.

There have been many times in my experimentation with nootropics that I’ve dosed a bit too high on compounds like DMAE, Alpha GPC, or CDP Choline, felt some of the above noted side effects and symptoms, and then within about 8 hours was feeling back to baseline again. One might call this “acute cholinergic dominance,” wherein in whatever fashion, in terms of quantity of acetylcholine, there is just too much.

It’s similar to drinking 1 too many cups of coffee, where you’ve told the brain that the neurotransmitter adenosine is not present, and thus, it’s nearly impossible for you to fall asleep at a normal hour. You’re in an excess of one effect, and it’s inhibiting or negatively effecting another.

You might be able to remedy acute cholinergic dominance by taking a nap to provoke a potential reset of neurotransmitter systems, taking an anticholinergic compound like a racetam, or by doing something else anticholinergic. In my anecdotal experiences through the years, I’ve been able to reduce symptoms of acute cholinergic dominance by accident after drinking a few beers. This could potentially be due to increases in GABA, and its effect on reducing neural activity by allowing chloride ions to enter the post-synaptic neuron. This may in fact modulate the acetylcholine content in the brain at the time, lowering it, and thus providing a relief from acute cholinergic dominance symptoms.

Long Term: 

This is where we dive deeper into the theoretical aspects of this dynamic, and look at what might be called long term cholinergic dominance. This is a state where, specifically through the continued use of certain cholinergic compounds, like Alpha GPC, CDP Choline, DMAE, or Centrophenoxine, the amount of acetylcholine being produced and put into circulation in the brain is vast. The mechanisms could also be related to increased acetylcholine receptor densities, making the brain more sensitive to acetylcholine as it passes from a presynaptic neuron to a postsynaptic neuron.

In the long term cholinergic dominant state, the side effects don’t seem to be as overt as that of the acute cholinergic dominance state in that there don’t seem to be too many negative side effects, but rather, a sort of residual enhancement in brain performance.

My personal experience with what I think to be long term cholinergic dominance has been quite interesting. Through the formulation of the nootropic stack Cortex, I was taking Uridine monophosphate and CDP Choline everyday for months. And sometimes, twice a day. I would dose both of these compounds in various quantities from 50MG of Uridine Monophosphate and 50MG of CDP Choline, all the way up to 500MG of each.

Throughout that process, I would certainly run into acute cholinergic dominance quite a lot, due to dosing too high, for my particular brain chemistry, with CDP and Uridine. But what’s been freakishly consistent about my experiences once the acute cholinergic dominance calmed down, and I went back to baseline, is that my baseline was in fact improved. It’s as if somehow, through the continued use of Uridine and CDP Choline, I’ve made what seem to be semi permanent changes in the acetylcholine, dopamine, and other systems of my brain.

It’s quite possible that I’ve provoked the facilitation of nerve growth factor, due to Uridine’s ability to improve neurite outgrowth, and it’s synergy with CDP Choline to help the brain synthesize phosphatidylcholine.

I seem to be more verbally fluent at baseline than I use to be. In past times, it would behoove me to take something like Triacetyluridine or a Uridine CDP combo before writing a long blog post or engaging in some type of cerebral work. These days, I can engage in those tasks quite effectively, with a great degree of focus, from baseline.

In conversations with people I never forget where we are in the conversation, or what one of the parties was just talking about. I’m always able to hold the entirety of the conversation in my working memory and often have to remind other parties of where were at. People wander endlessly, and never keep track of where they were to come back there.

And my brain’s overall ability to be fluid, in the face of my busy business life throwing curve balls at me virtually every day, has seen marked improvements.

Again, this is all my theory, and I’m not going to pretend this is all true and scientifically backed.

But one thing is for sure: people from all around the world, that experiment with nootropics, run into this very same thing, with these very same symptoms and positive effects, all of the time. And like I’ve laid out so far, it happens in relation to cholinergic supplementation. There is this infamous 94 page thread on Longecity that talks about a similar stack of combining DHA, Uridine, a choline source, and B vitamins, and there are reports of continued improvements in brain performance from its experimenters.

Racetams to reverse acute cholinergic (or long term) dominance

Another theory I have, that I have confirmed works quite well for me, is that once a person is in either an acute or long term cholinergic dominance, continued doses of the racetam smart drugs can reverse either the symptoms of acute cholinergic dominance, or the effects of long term cholinergic dominance.

For the latter, I hypothesize that this would take quite some time, because you’re undoing likely months or build up of acetylcholine, changes in acetylcholine receptor sites, and even possibly the accumulation of myelin around axons and dendrites. And based on said performance upgrades, you might not want to do that.

But for the former, it may be a good idea to get out of that depressed state of having entirely too much acetylcholine in your system at the time. And to do so, a few solid doses of a good racetam will help you right out of that problem.

A user named “askchris” on the nootropics subreddit, confirms this anecdotally by using Phenylpiracetam to abolish the negative effects of too much CDP Choline. And this has worked for me.

In a recent experience with acute cholinergic dominance, I dosed 700MG of Oxiracetam, by itself, and it pretty quickly took me out of the choline dominant state, and into a place where I was back to just above baseline. It seemed to even out the excess of acetylcholine I had accumulated from an earlier dose of Alpha GPC and CDP Choline.

I’ve used Aniracetam to do this same thing many times in the past, when through experimentation, I went entirely too high on the cholinergics, and needed to level out again. Of course, the proposed mechanism here is the utilization of acetylcholine in various regions on the brain, via the racetam smart drugs, thus taking acetylcholine levels back to baseline.

In summary, I don’t usually recommend taking any nootropics to extreme levels where you’re going to run into a major surplus of a particular neurotransmitter, and thus invoke side effects. But such is the nature of Cognitive Biohacking I suppose. If you do end up in a place of cholinergic dominance, whether its short term and long term, I hope this article can be of help to you. Thanks for reading.[/vc_column_text][vc_text_separator title=”Snag a bottle of our flagship nootropic, Cortex Generation 1″][vc_column_text]Cortex Nootropic Stack
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