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Is Too Much Acetylcholine Bad & What Reduces Its Levels?

Written by Puya Yazdi, MD | Last updated:
Jonathan Ritter
Matt Carland
Medically reviewed by
Jonathan Ritter, PharmD, PhD (Pharmacology), Matt Carland, PhD (Neuroscience) | Written by Puya Yazdi, MD | Last updated:

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Acetylcholine neuroscience: can too much of this neurotransmitter be bad?
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The brain needs acetylcholine to form memories. The nerve bundles of our “rest-and-digest” system require it to balance “fight-or-flight” activity. But can too much acetylcholine be bad? Check out this post to learn when an excess of this neurotransmitter might be unwanted and whether lowering its levels or activity can be beneficial.

Can You Have Too Much Acetylcholine?

Research Interpretation

Due to its wide range of roles throughout the body and brain, high acetylcholine levels, or activity in certain brain areas have been implicated in the development, progression, or symptoms of some health conditions listed in this article.

However, most of the studies we bring up dealt with associations only, which means that a cause-and-effect relationship hasn’t been established.

For example, just because depression has been linked with higher acetylcholine activity in certain brain areas doesn’t mean that depression is caused by too much acetylcholine. Data are lacking to make such claims. 

Also, even if a study did find that too much acetylcholine contributes to depression, acetylcholine levels are highly unlikely to be the only cause. Complex disorders like depression always involve multiple possible factors – including brain chemistry, environment, health status, and genetics – that may vary from one person to another.

Measuring Acetylcholine Levels

Assessing acetylcholine levels in the brain is extremely difficult. This is mostly because acetylcholine levels can’t be directly measured. A direct measurement would require brain tissue, blood from the brain’s circulation, or cerebrospinal fluid.

Even with indirect measurements (using state-of-the-art brain imaging techniques), acetylcholine levels may vary across brain areas and quickly change depending on many factors.

Therefore, whether or not a person can have “too much acetylcholine” is highly uncertain. However, science has suggested a link between certain health conditions and higher acetylcholine levels or activity in specific brain areas.

Currently, no direct-to-consumer test can assess acetylcholine levels. Clinical studies can estimate acetylcholine levels using brain imaging, but no definition of “excess acetylcholine” has been widely accepted.

Is Too Much Acetylcholine Bad?

There are no symptoms associated with high acetylcholine levels per se. Instead, people may only show symptoms of mental health, neurocognitive, or immune disorders. Your doctor will discuss your symptoms with you and run tests to pinpoint the underlying cause.

Low or high acetylcholine levels don’t necessarily indicate a problem if there are no symptoms or if your doctor tells you not to worry about it.

Associated Conditions:

1) Depression

Although serotonin is the neurotransmitter most commonly associated with depression and other mood disorders, other major neurotransmitters — including acetylcholine — may also play important roles in these psychiatric conditions.

Although the exact role of acetylcholine in depression is not yet fully understood, a handful of preliminary animal studies have reported that drugs that block nicotinic acetylcholine receptors (nAChRs) — such as mecamylamine — appear to have “antidepressant-like” effects in rodents [1, 2].

Building on this, according to two early phase-II clinical trials in humans with treatment-resistant depression (TRD), mecamylamine was reported to alleviate some depression symptoms when used in combination with more traditional antidepressants (such as selective serotonin reuptake inhibitors, or SSRIs) [3].

Nonetheless, while acetylcholine may play some role in depression, it is likely to be only one piece of a much larger and more complex puzzle. In the meantime, most scientific research on the development and treatment of depression will likely continue to focus primarily on the role of other neurotransmitters, such as serotonin, which have relatively much more research behind their role in depression and mood disorders.

Aside from serotonin, acetylcholine may also affect mood. Blocking acetylcholine seems to have antidepressant effects, but we don’t know whether too much acetylcholine can cause depression.

Smoking And Depression

Interestingly, some of the preliminary findings described above may account for some of the widespread associations that many studies have reported between smoking and depression [4, 5, 6].

Specifically, some researchers have proposed that short-term (acute) nicotine exposure can result in a reduction (“down-regulation”) of acetylcholine receptors [7]. This may initially produce an “antidepressant” or “anti-anxiety” effect in relatively new smokers, which could, in turn, contribute to the development of an addiction to (or dependence on) nicotine.

However, chronic exposure to nicotine may eventually cause nicotinic acetylcholine receptors to actually increase in number, which would reverse these initial effects. Therefore, smoking may actually lead to increased negative moods and anxiety in the long term [8, 9].

These adverse long-term effects, then, could potentially explain why rates of depression and other mood disorders tend to be higher in people who smoke [4].

Stimulating acetylcholine’s nicotinic receptors may have anti-anxiety effects in the short term, which can be addictive. But in the long term, this type of stimulation appears to worsen both anxiety and mood.

2) Hives

Scientists think that high acetylcholine may contribute to hives, as immune cells produce histamine in response to it [10, 11].

According to one unverified hypothesis, people with hives seem to have higher acetylcholine in the skin, but their cells are less sensitive to it. This causes issues with sweating and histamine release. Drugs that block acetylcholine are being investigated for preventing outbreaks, but their effectiveness is still uncertain [10, 11].

3) Sleep Cycle Alterations

Acetylcholine increases during the dreaming, REM phase of sleep. Limited data suggest that choline supplements may even induce lucid dreaming by boosting acetylcholine in the brain. Acetylcholine levels are low during restorative, slow-wave sleep, during which memory is consolidated [12, 13].

Too much acetylcholine has been implicated in hives. High levels might also bring about lucid dreaming. More research in these areas is needed.

Factors That May Decrease Acetylcholine Levels

Because low acetylcholine is believed to be involved in the development of some diseases, there are many potential uses that have been proposed for substances that can block the acetylcholine system.

List of Supplements & Nutrients

Many compounds and drugs may decrease acetylcholine levels or reduce its activity.

In general, drugs or other compounds that reduce acetylcholine levels — or otherwise inhibit its activity — are commonly known as “anticholinergics.” (To learn more about these substances and how they work, we recommend checking out our detailed SelfHacked posts on anticholinergics, which you can find here and here.)

Once again, these drugs may exert this effect by targeting one or more of the multiple different potential mechanisms and pathways related to the creation or release of acetylcholine.

Some of the supplements and dietary compounds that have been proposed to have some potential anticholinergic effects and mechanisms include:

On the other hand, the following are synthetic compounds, plant toxins, and heavy metals that may lead to unwanted effects or poisoning by acting on the same pathway:

Some natural compounds like forskolin and lipoic acid may reduce acetylcholine activity or levels. They are collectively known as anticholinergics.

When to See a Doctor

If you believe you have a health condition or other reason to try to influence your acetylcholine levels, it is extremely important to always talk to your doctor about any new supplements or dietary changes you make.

The approaches discussed in this post could interact with any other drugs you are taking, other pre-existing health conditions, and other health-related factors. None of the information in this post should ever be used to replace conventional medical treatment.

It is also important to keep in mind that many of the compounds and substances discussed above have only been tested in animal- or cell-based studies. This means that their effects and overall safety in healthy human users is not known.

Therefore, these compounds should be considered as currently having “insufficient evidence” for any specific use — and much more research will be needed to verify what effects they may have in humans, as well as how safe they may be.

Blocking Acetylcholine Is Not that Simple

Many biological processes and pathways are involved in determining the total amount of acetylcholine in the body and brain, as well as its overall degree of activity.

This means that there are many different mechanisms and pathways that can influence acetylcholine, such as:

  • Increasing or decreasing the levels of its “ingredients” (metabolic precursors), such as choline
  • Activating or inhibiting the enzymes that produce (synthesize) active acetylcholine from its precursors, such as choline acetyltransferase or acetyl-coenzyme A
  • Stimulating or suppressing the release of acetylcholine by nervous system cells
  • Directly activating acetylcholine receptors, such as by “imitating” natural (“endogenous”) acetylcholine
  • Blocking acetylcholine receptors, thereby preventing them from being activated by natural acetylcholine
  • Increasing or decreasing the number of acetylcholine receptors

Takeaway

Acetylcholine is usually seen as the “good guy” since it activates the “rest-and-digest” system and promotes wakefulness. It might also induce lucid dreaming.

However, experimental research suggests an association between too much acetylcholine and certain health problems. Still, it’s hard to define “excess acetylcholine” since this neurotransmitter can’t be directly measured and its levels may vary across different brain areas.

Nonetheless, scientists think that a dominance of acetylcholine may be linked with depression and hives. Natural compounds like forskolin and kava may supress acetylcholine activity, but their health benefits are uncertain.

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About the Author

Puya Yazdi

Puya Yazdi

MD
Dr. Puya Yazdi is a physician-scientist with 14+ years of experience in clinical medicine, life sciences, biotechnology, and nutraceuticals.
As a physician-scientist with expertise in genomics, biotechnology, and nutraceuticals, he has made it his mission to bring precision medicine to the bedside and help transform healthcare in the 21st century.He received his undergraduate education at the University of California at Irvine, a Medical Doctorate from the University of Southern California, and was a Resident Physician at Stanford University. He then proceeded to serve as a Clinical Fellow of The California Institute of Regenerative Medicine at The University of California at Irvine, where he conducted research of stem cells, epigenetics, and genomics. He was also a Medical Director for Cyvex Nutrition before serving as president of Systomic Health, a biotechnology consulting agency, where he served as an expert on genomics and other high-throughput technologies. His previous clients include Allergan, Caladrius Biosciences, and Omega Protein. He has a history of peer-reviewed publications, intellectual property discoveries (patents, etc.), clinical trial design, and a thorough knowledge of the regulatory landscape in biotechnology.He is leading our entire scientific and medical team in order to ensure accuracy and scientific validity of our content and products.

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