Is Too Much Acetylcholine Bad & What Reduces Its Levels?

Causes of Alzheimer’s Disease Continued

Is Too Much Acetylcholine Bad & What Reduces Its Levels?
The AD Brain – Plaques and Tangles

When compared to the brains of people who are aging normally, the brains of people who have AD contain large numbers of plaques, particularly in the hippocampus, the region of the brain that controls memory. In addition, individuals with AD have a significant amount of neurofibrillary tangles spread throughout the brain.

Interestingly, doctors have found some people who showed no symptoms of Alzheimer's Disease and still had a significant number of plaques and tangles in their brains at autopsy.

These people may have developed a so called “cognitive reserve,” or a large number of connections between brain cells due to healthy lifestyle habits (discussed later) and a high level of education which acted a “buffer” to stave off the symptoms of the disease.

Another theory is that plaques and tangles begin to form several years before Alzheimer's symptoms actually appear, so people who have plaques and tangles but no signs of AD may have died of another cause before living long enough to become cognitively impaired.

Because of this mystery (why some people with large amounts of plaques and tangles don't have AD symptoms), many scientists believe there is more to Alzheimer's Disease than abnormal protein accumulations, although these do seem to play a significant role in the development of the disease.

The AD Brain – Free Radicals

Individuals with Alzheimer's Disease seem to have double the amount of destruction created by free radicals in the frontal and temporal (side) portions of the brain when compared to people aging normally. Both of these brain areas are important for memory and other advanced cognitive functions.

The AD Brain – Neurotransmitters

Neurotransmitters are chemicals that carry messages between neurons so that the cells can function properly. If the brain produces too much or too little of a particular neurotransmitter, problems such as memory impairment, confusion, or depression can occur.

While most scientists do not think that changes in neurotransmitter levels cause AD, neurotransmitter levels are affected by the illness and contribute to the thinking problems that accompany it.

Several medications used to treat symptoms of Alzheimer's Disease target neurotransmitters, which provides indirect evidence that these brain chemicals are somehow involved.

Two neurotransmitters seem to play a role in Alzheimer's Disease: acetylcholine and glutamate. Acetylcholine (ACh) activates muscles and helps with arousal, short-term memory, and learning. Individuals with AD have low levels of ACh.

Some research suggests that plaques may be one of the reasons for low levels of ACh because they increase the activity of a chemical called acetylcholinesterase, which is involved in breaking down ACh.

Too much acetylcholinesterase has the overall effect of decreasing ACh levels, which contributes to the characteristic symptoms of AD.

Glutamate is the most common neurotransmitter in the brain and is involved in learning and memory. As the brain cells of someone with Alzheimer's Disease die, they release excess amounts of glutamate. The excess glutamate becomes harmful because it overstimulates healthy brain cells (a phenomenon called excitotoxicity), causing them to become damaged or to die.

The AD Brain – The Path of Destruction

AD starts in a part of the brain called the entorhinal cortex (EC), which sends signals to the hippocampus that help form and store memories.

Plaques and tangles then spread to the hippocampus and other parts of the brain that control memory, language, and reasoning. As brain regions are destroyed, they atrophy or shrink.

As a result, the fluid-filled chambers of the brain (called ventricles) enlarge, and sulci (tissue indentations) widen. Eventually, large portions of the brain are completely destroyed by AD.


Is Too Much Acetylcholine Bad & What Reduces Its Levels?

Acetylcholine is a chemical messenger, or neurotransmitter, that plays an important role in brain and muscle function. Imbalances in acetylcholine are linked with chronic conditions, such as Alzheimer’s disease and Parkinson’s disease.

Acetylcholine was the first neurotransmitter discovered.

Imbalances in levels of acetylcholine play a role in some neurological conditions. People who have Alzheimer’s disease and Parkinson’s disease tend to have low levels of acetylcholine.

There is no proven way to maintain ideal levels of acetylcholine and prevent neurological diseases. However, researchers are developing advanced treatments to help people with these health conditions live longer, healthier lives.

In this article, we look at how acetylcholine is linked with various health conditions, including Alzheimer’s disease, myasthenia gravis, and Parkinson’s disease. We also discuss treatments for acetylcholine-related conditions.

Alzheimer’s disease is the most common cause of dementia among older adults, according to the National Institute on Aging.

Its symptoms include severe memory loss and problems with the ability to think that interfere with daily life. There is no cure for Alzheimer’s disease.

Experts do not know what causes Alzheimer’s disease. However, they know that many people with the condition have lower levels of acetylcholine. Alzheimer’s disease damages cells that produce and use acetylcholine.

Certain medications can increase levels of acetylcholine. They do this by blocking the action of enzymes that break down the neurotransmitter.

The primary enzyme in this group is called acetylcholinesterase (AChE), and drugs that make these enzymes less active are called AChE inhibitors or cholinesterase inhibitors.

AChE inhibitors can help with symptoms related to thought processes such as language, judgment, and memory.

AChE inhibitors include:

  • donepezil (Aricept)
  • galantamine (Razadyne)
  • rivastigmine (Exelon)

AChE inhibitors may also help treat other health conditions. Some tumors appear to have an unusual level of AChE in them, according to some research. Scientists may find that AChE inhibitors can help treat certain types of cancer.

Myasthenia gravis is an autoimmune condition that causes muscle weakness, especially after a person is active.

Myasthenia gravis causes the immune system to block or destroy acetylcholine receptors. Then, the muscles do not receive the neurotransmitter and cannot function normally. Specifically, without acetylcholine, muscles cannot contract.

Symptoms of myasthenia gravis can range from mild to severe. They may include:

  • weakness in the arms, legs, hands, fingers, or neck
  • drooping of one or both eyelids
  • blurred or double vision
  • trouble swallowing
  • shortness of breath
  • difficulty speaking

Many people with myasthenia gravis can lead regular lives. A variety of treatments can control symptoms.

AChE inhibitors that doctors prescribe to treat Alzheimer’s disease may also help relieve symptoms of myasthenia gravis. When these drugs slow the breakdown of acetylcholine, they improve neuromuscular connection and muscle strength.

An imbalance in levels of acetylcholine may have an effect in people with Parkinson’s disease, too.

The body needs a balance of acetylcholine and dopamine, another chemical messenger, to control movements well.

Parkinson’s disease is a neurodegenerative condition that causes involuntary movements, tremors, and difficulties with thinking and mood.

The exact causes of Parkinson’s disease are unknown. However, experts have discovered that people with the condition often have a decrease in dopamine that allows acetylcholine to take over. When this occurs, muscles become too “excited,” which leads to symptoms such as jerking movements and tremors.

For this reason, some medications for Parkinson’s disease block the action of acetylcholine. This allows dopamine levels to rebalance, which can help relieve some symptoms.

These medications are called anticholinergics. They can also help ease dyskinesias, which are excessive movements that can be side effects of other Parkinson’s medications.

Anticholinergics are not for everyone. Side effects may include confusion, memory loss, hallucinations, and blurry vision.

Experts also believe that many nonmotor symptoms of Parkinson’s disease, such as memory problems, are related to reduced levels of acetylcholine.

Share on PinterestA buildup of acetylcholine in the nervous system may cause headaches, weakness, and mental changes.

Exposure to organophosphate (OP) pesticides or certain nerve agents used in warfare can cause levels of acetylcholine in the body to rise very high.

The Centers for Disease Control and Prevention (CDC) say that these chemicals lead to a buildup of acetylcholine in the nervous system, causing symptoms of:

  • wheezing
  • sweating
  • weakness
  • headaches
  • fainting
  • diarrhea and vomiting
  • mental changes
  • muscle twitching
  • convulsions
  • paralysis
  • respiratory arrest

A person can be exposed to these chemicals through the skin, through breathing, or through ingestion. In the United States, about 8,000 people a year are exposed to OPs.

Exposure is most ly to occur through contact with pesticides on crops — including apples, grapes, spinach, cucumbers, and potatoes — or through contact with household products such as ant and roach killers.

There is no proven way to increase acetylcholine levels. However, some evidence suggests that consuming choline, a nutrient, could help.

The body requires choline for proper brain and nervous system function. It is also necessary for muscle control and to create healthy membranes around the body’s cells.

Choline is also a building block of acetylcholine. People must get enough choline from their diets to produce adequate levels of acetylcholine.

Studies in animals have found that a high intake of choline during gestation and early development improves cognitive function and helps prevent age-related memory decline.

The Office of Dietary Supplements confirm that some animal studies have shown that higher intakes of choline could lead to better cognitive function. However, they caution, other studies have found it to be unhelpful.

Many foods contain choline, including:

  • meat
  • fish
  • eggs
  • beans
  • cruciferous vegetables
  • whole grains
  • dairy products
  • nuts
  • seeds

Most people do not get enough choline from their diets. The recommended amount of choline is 425 milligrams (mg) per day for women and 550 mg for men.

A person can take choline supplements, but high doses can cause side effects such as vomiting, a fishy body odor, and liver damage.

Share on PinterestBotox injections may reduce wrinkles in the face.

Botulinum toxin, better known by the brand name Botox, can treat a variety of muscle-related conditions. Botox injections can also treat migraine headaches, excessive sweating, and certain bladder and bowel issues, for example.

In addition, Botox is the most popular nonsurgical cosmetic treatment in the U.S., according to the American Society of Plastic Surgeons.

Botox primarily works by interfering with acetylcholine in the targeted muscle. Injecting Botox into certain facial muscles, for example, can create a temporary reduction in wrinkles because Botox prevents the muscles from contracting. This causes the skin on top of the muscle to appear smoother.

Acetylcholine is an important and abundant neurotransmitter in the body. When there is too much or too little, a person may experience neurological problems, such as those that characterize Alzheimer’s disease or Parkinson’s disease.

Eating a healthful diet can help a person get adequate choline, which the body uses to create acetylcholine. Ask a doctor before taking choline supplements, due to their potentially serious side effects.


Is Too Much Acetylcholine Bad & What Reduces Its Levels?

Is Too Much Acetylcholine Bad & What Reduces Its Levels?

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.

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 unly to be the only cause. Complex disorders 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.

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.

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-” 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 ly 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 ly 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.

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].

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].

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:

  • Forskolin [14]
  • Kava root [15, 16]
  • Lipoic Acid [17]

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:

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


Top 10 Symptoms of Low Acetylcholine – Parasym Plus™

Is Too Much Acetylcholine Bad & What Reduces Its Levels?

Acetylcholine is a neurotransmitter — a chemical messenger that allows your nerves to communicate with each other and with our organs. It is important to identify the symptoms of low acetylcholine because acetylcholine is our most common neurotransmitter and is used throughout our nervous system.

Central Nervous System

In the brain (the central nervous system) acetylcholine allows your neurons to communicate making it possible for you to think clearly and to form short-term memories. Without optimal acetylcholine levels in the brain, cognition becomes sluggish causing “brain fog”.

Peripheral Nervous System

Your muscles use acetylcholine, too (the peripheral nervous system).  Low acetylcholine levels can result in weakness and fatigue.

Autonomic Nervous System

Acetylcholine is also required by the autonomic nervous system — the system of the body that you don’t need to think about.

  The functions of the autonomic nervous system include heart rate, blood pressure, breathing, blinking, digestion, and many others! The autonomic nervous system controls your vagus nerve which is the anti-inflammatory system of the body. When it is not performing optimally, chronic inflammation can occur.

Your vagus nerve (via the messenger acetylcholine) controls every aspect of digestion including: movement of food through the upper GI tract beginning with swallowing, normal stomach acid production, the opening of the pyloric valve at the base of the stomach allowing food to pass into the intestines, movement of stool through the intestines, gallbladder functioning to release bile for digestion of fats, pancreatic functioning to release digestive enzymes, and movement of the stool (“peristalsis”) to trigger a bowel movement.

Parasympathetic Nervous System

The parasympathetic nervous system — the “rest and digest” system of the body — depends upon acetylcholine as well. Acetylcholine is the chemical messenger that allows your body to calm down after a surge of adrenaline occurs — only then can you get in a relaxed state and begin digestion.

Some of the most common causes of low acetylcholine are genetic errors, chronic illness, chronic inflammation, some medications, and aging. Diagnosing low acetylcholine can be difficult since there is no blood test available; therefore low acetylcholine is a clinical diagnosis symptoms. Low acetylcholine levels can also occur in anticholinergic poisoning.

When patients ingest massive doses of anticholinergic medications (such as an accidental poisoning with atropine), anticholinergic poisoning occurs. The symptoms of anticholinergic poisoning are recognized presentation (clinical signs and symptoms). The symptoms of low acetylcholine are easy to miss because they can mimic many other conditions.

Doctors have a mnemonic to remember the presentation of low acetylcholine levels in anticholinergic poisoning: “Blind as a bat, dry as a bone, red as a beet, mad as a hatter, can’t see, can’t pee, can’t poop”. What do these symptoms mean and what other symptoms occur in anticholinergic poisoning?

Acetylcholine is the neurotransmitter needed by the neurons of the brain to communicate with each other. Low acetylcholine causes difficulties with cognition, “brain fog”, and mental fatigue.

Acetylcholine is required by the peripheral nervous system allowing muscles to work. Insufficient acetylcholine levels result in muscle weakness that worsen with exercise or exertion. The muscles may work for a while, then exhaust their supply of acetylcholine, leading to extreme fatigue.

The vagus nerve uses acetylcholine to assist every aspect of digestion including peristalsis (movement of food or stool through the digestive tract).

Stomach acid production, opening of the pyloric sphincter at the bottom of the stomach, gallbladder function, some pancreatic function, and opening of the Sphincter of Oddi (which allows bile and pancreatic enzymes to pass into the intestines). Therefore, low acetylcholine levels are especially detrimental to the digestive tract.

Because the vagus nerve is such an important part of the digestive tract low acetylcholine levels can be especially detrimental. Chronic constipation and/or gastroparesis. are very common symptoms of low acetylcholine.

Poor digestion and poor absorption of critical nutrients are also a common symptom of low acetylcholine potentially leading to malnutrition.

Normal tear production is a process of our autonomic nervous system. Acetylcholine is required by the lacrimal gland to produce tears.

Acetylcholine is also used by the nerves to tell our bodies when to produce tears. When levels of acetylcholine are low, dry, painful eyes can result.

Dry eyes  due to insufficient acetylcholine are resistant to conventional dry eye treatment unless acetylcholine levels are restored.

Sub optimal acetylcholine levels can cause low blood pressure when standing, causing dizziness and weakness.

Patients with low acetylcholine often experience episodes of flushing (redness) on the face. The neck and other parts of the body may also appear flushed. It is common for flushing to be misdiagnosed as rosacea or mast cell activation.

People with low acetylcholine levels often suffer from the inability to cope with their emotions. Their emotional state can be unpredictable.

Acetylcholine is needed by the vagus nerve (the anti-inflammatory pathway of the body). Low levels of acetylcholine contribute to consistently high inflammation which can cause pain, atherosclerosis, fatigue, hypercoagulation (easy blood clotting) and premature aging. Chronic inflammation is an often overlooked symptom of low acetylcholine which results in accelerated aging.

The parasympathetic nervous system is the body’s “rest and digest” system. When levels of acetylcholine are insufficient, the vagus nerve no longer slows down the heart. If the heart can not be properly slowed the body cannot rest. The vagus nerve relies upon acetylcholine to stimulate the sinoatrial node of the heart to normalize heart rate.

Pupil size is a function of the balance between the sympathetic nervous system (large pupils) and parasympathetic nervous system (small pupils). Sub optimal acetylcholine levels upset this balance.

When the balance is upset, the sympathetic nervous system overrides the parasympathetic nervous system, resulting in large pupils. Large pupils often cause light sensitivity and difficulty focusing.

If you have some of these symptoms and yet you have not been poisoned, you could be dealing with less than optimal levels of acetylcholine, perhaps due to genetics, aging, or inflammation.

The vagus nerve controls the digestion process. When acetylcholine is low, any breakdown in these mechanisms can result in the dysbiosis known as SIBO or SIFO.

Parasym Plus™ is the only product patented to nudge the vagus nerve PLUS it crosses the blood-brain barrier to support cognition. By supporting acetylcholine levels, Parasym Plus™ also helps maintain normal tear production.

Can something be done to optimize low acetylcholine levels? Can we provide what our bodies need in a way that also stimulates the vagus nerve?

Yes, we can.

Albuquerque, E X, et al. “Mammalian Nicotinic Acetylcholine Receptors: from Structure to Function.” Current Neurology and Neuroscience Reports., U.S. National Library of Medicine, Jan. 2009. [Full Article]

Albuquerque, E. “Chapter 9 Nicotinic Acetylcholine Receptors on Hippocampal Neurons: Cell Compartment-Specific Expression and Modulatory Control of Channel Activity.” NeuroImage, Academic Press, 29 Feb. 2008. [Full Article]

Blusztajn, J K, and R J Wurtman. “Choline and Cholinergic Neurons.” Current Neurology and Neuroscience Reports., U.S. National Library of Medicine, 12 Aug. 1983. [Full Article]

Cohen, EL, and Wurtman RJ. “Brain Acetylcholine: Increase after Systemic Choline Administration.” Addiction & Health, StatPearls Publishing, 1975. [Full Article]

Doležal, Vladimir, and Stanislav Tuček. “Utilization of Citrate, Acetylcarnitine, Acetate, Pyruvate and Glucose for the Synthesis of Acetylcholine in Rat Brain Slices.” The Canadian Journal of Chemical Engineering, Wiley-Blackwell, 5 Oct. 2006. [PubMed]

Ferreira-Vieira, T H, et al. “Alzheimer’s Disease: Targeting the Cholinergic System.” Current Neurology and Neuroscience Reports., U.S. National Library of Medicine, 2016. [Full Article]

Ge, Shaoyu, and John A. Dani. “Nicotinic Acetylcholine Receptors at Glutamate Synapses Facilitate Long-Term Depression or Potentiation.” Journal of Neuroscience, Society for Neuroscience, 29 June 2005. [Full Article]

Hasselmo, Michael. “The role of acetylcholine in learning and memory.” Addiction & Health, StatPearls Publishing, 2006. [Full Article]

Klinkenberg, I, et al. “Acetylcholine and Attention.” Current Neurology and Neuroscience Reports., U.S. National Library of Medicine, 10 Aug. 2011. [Full Article]

Micheau, J, and A Marighetto. “Acetylcholine and Memory: a Long, Complex and Chaotic but Still Living Relationship.” Current Neurology and Neuroscience Reports., U.S. National Library of Medicine, 10 Aug. 2011. [PubMed]


Potential Root Cause of Depression Discovered by NARSAD Grantee

Is Too Much Acetylcholine Bad & What Reduces Its Levels?

From The Quarterly, Spring 2013

Marina Picciotto, Ph.D., leading a team of researchers at Yale University, has made an exciting discovery in the search for the biological causes of depression and anxiety. Their discovery points to the importance of a signaling system in the brain that was not previously believed to be central in causing depression.

For decades, many scientists have favored a theory of depression that stresses the impact of abnormally low levels of a signal-carrying chemical, called serotonin. The new research by Dr. Picciotto’s team shifts attention to a different signaling chemical, or neurotransmitter, called acetylcholine.

Millions of depressed people take anti-depressant drugs called SSRIs—an acronym for selective serotonin re-uptake inhibitors.

Prozac®, Paxil®, Celexa®, Zoloft® and other SSRI medications act to keep message-carrying serotonin molecules from being rapidly reabsorbed by nerve cells.

By allowing serotonin to float for longer periods of time in the tiny spaces between nerve cells, called synapses, scientists have theorized the SSRI drugs promote signaling by compensating for abnormally low serotonin levels.

Dr. Picciotto’s new research, published in Proceedings of the National Academy of Sciences in February, turns attention to fluctuations in levels of the neurotransmitter acetylcholine and the larger chemical signaling system it is part of, called the cholinergic system.

“Serotonin may be treating the problem,” Dr. Picciotto says, “but acetylcholine disruption may be a primary cause of depression. If we can treat the root cause, perhaps we can get a better response from the patient.”

Her team’s experiments demonstrate that abnormally high levels of acetylcholine in the brain can cause depression and anxiety symptoms in mice.

In the brains of non-depressed mice—and people—an enzyme called acetyl- cholinesterase (AChE) is produced to lower acetylcholine levels.

The team showed that when depressed mice were given Prozac®, AChE levels were raised, and abnormally high levels of acetylcholine were thus brought under control. This adds a new dimension to understanding how and why SSRI anti-depressants can alleviate depression.

Yet many depressed people do not get a therapeutic benefit from Prozac® or other SSRI medications. Dr.

Picciotto’s research suggests this may be because the root problem is not, after all, low levels of serotonin, but rather, high levels of acetylcholine.

By experimentally blocking the “ports,” called receptors, where acetylcholine molecules “dock” with nerve cells in the brain, the team was able to reverse depression in mice.

In still other experiments, the Yale team showed how interruptions in acetylcholine signaling in the brain area called the hippocampus—important in memory and mood—promotes depression and anxiety in mice.

While the relation between the serotonin and acetylcholine signaling systems is not yet fully clear, this new research opens a new possibility to treat the cause of depression and not just its symptoms.

With the new hypothesis that it is the disruption of acetylcholine, and not serotonin, that sets depression in motion, further research studies can be undertaken to determine if medications that target acetylcholine rather than serotonin, are more effective in treating depression.

Marina Picciotto, Ph.D.Charles B. G. Murphy Professor of Psychiatry,Professor of Neurobiology and Pharmacology,Assistant Chair for Basic Science Research, Psychiatry,Yale University;

1996 NARSAD Young Investigator Grantee,

2004 NARSAD Independent Investigator Grantee


Acetylcholine (Neurotransmitter)

Is Too Much Acetylcholine Bad & What Reduces Its Levels?

The neurotransmitter acetylcholine affects thinking and movement. An acetylcholine imbalance can cause mental problems that involve cognition (thinking, learning, memory, understanding, etcetera).

In addition, an imbalance of acetylcholine may be responsible for physical problems that include dry mouth, gastrointestinal maladies, twitching and convulsions that cause uncontrollable movement, paralysis (not being able to move at all).

Areas of the human body that utilize or are affected by acetylcholine are called cholinergic. Substances that produce similar effects to acetylcholine are called cholinergic. Substances that impede acetylcholine activity are called anticholinergic.

Low Acetylcholine Levels
Increasing Acetylcholine Levels
High Acetylcholine Levels
Decreasing Acetylcholine Levels
Acetylcholine And Racetams
Acetylcholine Related Notes
Acetylcholine Related Links

Symptoms Of Low Acetylcholine Levels

Acetylcholine levels may be reduced by things genetics, stress, vitamin deficiency, limited sleep, high blood sugar levels, hazardous chemicals. People who consume alcohol regularly and endurance athletes may have a greater risk of deficiency.

Mental symptoms associated with low acetylcholine levels include: — Anxiety. — Moodiness. — Memory Loss. — Disorientation. — Impaired Thinking. — Learning Disabilities.

— Difficulty Comprehending Language (spoken or written).

Low levels of acetylcholine may interfere with cognition. Individuals diagnosed with Dementia and Alzheimer's Disease have lower levels of acetylcholine in their brains, when compared to people who do not suffer from these illnesses.

Physical symptoms linked to low acetylcholine levels include: — Dry Mouth. — Nerve Damage. — Lack Of Energy. — Pain (mainly in muscles).

— Difficulties With Movement.

Reduced levels of acetylcholine can have an effect on mobility. Substances that prevent a neuron from releasing acetylcholine can cause paralysis. Substances that bind to and block acetylcholine receptors (antagonists) can also cause paralysis.

If you have symptoms that you think might be related to a lack of acetylcholine, it is a good idea to your doctor or consult a qualified health care practitioner. If left untreated, low levels of acetylcholine can lead to serious permanent health issues.

How To Increase Acetylcholine Levels

Acetylcholinesterase inhibitors slow the breakdown of acetylcholine. This results in increased levels of acetylcholine and acetylcholine having a longer duration of action.

Choline is converted to acetylcholine in the human body. For most healthy individuals with low acetylcholine levels, they can be increased by eating foods that contain choline, taking choline supplements, or in some other way ingesting choline.

Supplements with a relatively high choline content include: — Alpha-GPC. — Citicoline (CDP choline).

— Other supplements that contain choline.

Foods that contain choline include: — Milk. — Eggs. — Spinach. — Chicken. — Broccoli. — Tofu (firm). — Cauliflower. — Wheat Germ. — Brewer's Yeast. — Chicken Breast. — Kidney Beans (cooked). — Lean Beef (especially liver). — Products that contain soybean. — Fish (especially cod and salmon).

— Nuts (especially almonds and peanuts).

Symptoms Of High Acetylcholine Levels

There are individuals who associate high acetylcholine levels with improved brain function and being smarter. As a result, they may eat large amounts of food that contain choline or take choline supplements to boost acetylcholine.

This is usually not a problem but can be taken to a point where it increases acetylcholine to excessive levels, and unintentionally ends up being detrimental instead of beneficial. It is true that not enough acetylcholine can interfere with thinking

If low levels continue for extended periods of time they can end up causing permanent problems. But if acetylcholine levels are within normal ranges, increasing them will not result in better brain function.

Too much acetylcholine can interfere with thinking and learning as much as too little. If you decide to follow a diet that includes large quantities of choline, or take choline supplements, do so in moderation.

High acetylcholine levels are generally not a problem with healthy individuals who eat a balanced diet. However, some medications and illnesses may contribute to increased acetylcholine and cause problems.

Symptoms of excessive acetylcholine levels may include: — Impaired Thinking (confusion, memory loss…). — Feeling Tired (without a reason). — Blurred vision. — Depression. — Irritability. — Headache. — Dry mouth. — Stomach Problems. — Nausea and Vomiting. — Pain (especially in muscles and joints).

— Muscle Twitching and Convulsions (followed by paralysis).

How To Decrease Acetylcholine Levels

For those people that are sure that there is a need to reduce the effects of high levels of acetylcholine, substances referred to as anticholinergics may be appropriate. Consult a physician before taking anticholinergics.

Anticholinergics inhibit acetylcholine from working by blocking acetylcholine from binding to and triggering acetylcholine receptors in nerve cells located in the central and the peripheral nervous system.

Anticholinergics can be divided into three categories depending on their specific targets in the central and/or peripheral nervous system. They are antimuscarinic agents, ganglionic blockers, neuromuscular blockers.

Several hundred compounds have anticholinergic properties. They include over-the-counter drugs and prescription medications. Some of those medications include:

— Antiarrhythmics (Disopyramide, Procainamide, Quinidine). — Antiemetics (Dimenhydrinate, Meclizine, Prochlorperazine). — Antihistamines (Azatadine, Diphenhydramine, Hydroxyzine).

— Antiparkinson Agents (Benztropine, Biperiden, Procyclidine). — Antipsychotics (Chlorpromazine, Clozapine, Mesoridazine). — Antispasmodics (Atropine, Belladonna, Scopolamine). — Muscle Relaxants (Carisoprodol, Cyclobenzaprine).

— Tricyclics (Amitriptyline, Imipramine, Nortriptyline).

Many antihistamines including benadryl (diphenhydramine) are available over-the-counter, and act as fairly effective as anticholinergics. Other medications listed above that have anticholinergic properties might require a prescription.

Be aware that anticholinergic substances may cause unwanted side effects that include confusion, constipation, disorientation, hallucinations, blurred vision, dry mouth, flushed skin, slurred speech, urinary retention, less control of bodily movements.

Long term use of anticholinergic substances can contribute to problems dementia. They can cause anticholinergic syndrome, a group of symptoms caused by reduced acetylcholine levels or inhibiting neurotransmission of acetylcholine.

Nicotine and caffeine can be used as an anticholinergic syndrome antidote. Nicotine by activating nicotinic acetylcholine receptors. Caffeine by reducing sedation and increasing the activity of acetylcholine. Another substance for this purpose is physostigmine (also called eserine).

Acetylcholine And Racetams

Acetylcholine use in the body is affected by at least some, and probably most if not all, of the group of drugs known as racetams. Racetams can improve thinking, reduce anxiety, reduce or eliminate depression.

One of the ways that racetams are thought to work includes utilizing acetylcholine more efficiently. Because of this, racetams that affect acetylcholine may be of value to those experiencing problems related to acetylcholine levels in the body.

Racetams may cause some people who consume them to experience headaches. By taking them with a choline source, ( alpha-GPC or citicoline) headaches can be reduced or eliminated. Choline may also increase the potency of racetams.


1 — Substances classified as acetylcholine receptor agonists and acetylcholine receptor antagonists can affect the acetylcholine receptors themselves, or act in an indirect manner by affecting the enzyme acetylcholinesterase.

2 — Acetylcholine receptors in the body include: a) Nicotinic acetylcholine receptors (nAChR) also called ionotropic acetylcholine receptors are very responsive to nicotine.

b) Muscarinic acetylcholine receptors (mAChR) also called metabotropic acetylcholine receptors respond to muscarine.

3 — Acetylcholine is involved with REM sleep. REM is a sleep stage associated with dreaming. Some drugs racetams and acetylcholinesterase inhibitors may induce more vivid dreams, and be of interest to those interested in lucid dreaming.

4 — If your body has a negative reaction to choline in foods or supplements, possible troubles may include: — Excessive Sweating. — Nausea and Vomiting. — Upset Stomach and Diarrhea.

— Other Gastrointestinal Problems (stomach and intestines).

Anticholinergic drugs dementia risk.
Medications with anticholinergic properties.
Symptoms of excessive levels of acetylcholine.
Wikipedia acetylcholine page.
Wikipedia choline page.
Wikipedia cholinergic page.
Wikipedia anticholinergic page.