What is Acetylcholine?

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Acetylcholine might not get talked about as much as neurotransmitters like dopamine and serotonin, but it actually plays an exciting role in your body—quite literally. Acetylcholine's primary role is excitatory, meaning it causes action. It was also the first neurotransmitter ever discovered, and the one scientists know the most about.^[1] Here, you'll learn all you need to know about the fascinating role this neurotransmitter plays in your body, as well as what scientists are learning about how it affects your brain functioning and mental health.

What is acetylcholine?

Acetylcholine is an amino acid that acts as a neurotransmitter. Neurotransmitters send messages from one neuron to another in your nervous system. As one of the most plentiful neurotransmitters, acetylcholine plays a role in literally every move you make and every breath you take. The system of neurons and specialized cells that send and receive acetylcholine—the "cholinergic system"—runs throughout your entire body.^[2]

Your body produces its own acetylcholine, in part using choline the body gets from foods you eat. Egg yolks, legumes, and seeds are some of the foods that are rich in choline.
While scientists know a lot about how acetylcholine affects the movement of your skeletal muscles, the neurotransmitter's role in the brain and central nervous system is not as well understood.^[3]

Functions of Acetylcholine

Movement. Acetylcholine is active at the neuromuscular junction, a specialized connection between your muscles and your nerves. By passing over this junction, acetylcholine stimulates muscle contraction and movement.^[4]

To better understand how this works, consider what happens when you pick up an object. Think of all the tiny muscles in your hand that have to move for you to grasp the object and hold it firmly. Acetylcholine sent the message that triggered each of those muscles to contract.
When you're bitten by a black widow spider, the venom stimulates a flood of acetylcholine that causes excessive muscle contractions. Eventually, all of your acetylcholine will be released, resulting in paralysis.^[5]

Smooth muscle contraction. Smooth muscles are the muscles that make all of your organs function. Acetylcholine sends the message for these muscles to contract, which aids your digestion, heart rate, and breathing.^[6]

In your cardiovascular system, acetylcholine decreases your heart rate, and reduces the force of cardiac muscle contractions. It also dilates your blood vessels to lower your blood pressure.
In your lungs, acetylcholine helps you breathe more deeply and take more air into your lungs.
In your eyes, acetylcholine causes your pupils to dilate in response to light and helps you focus.
These contractions also stimulate secretions, so you can thank acetylcholine every time you sweat or salivate.
In the male reproductive system, acetylcholine is also responsible for erections.

Sensory gating. Sensory gating describes the process your brain uses to filter out background noise so that you can focus. Acetylcholine triggers the "gating" process by dampening or blocking irrelevant or redundant noises to the background. There is speculation that increasing acetylcholine levels could help people who have problems with sensory gating.^[7]

A sensory gating deficit is an important symptom of many mental disorders, including bipolar disorder, post-traumatic stress disorder (PTSD), and schizophrenia.
People with traumatic brain injury (TBI) and epilepsy also have a high likelihood of experiencing a sensory gating deficit.

Learning. Acetylcholine enhances the coding of new information in your brain. By continually stimulating specific individual neurons in your brain, the neurotransmitter encourages you to actively remember new things and connect them to things you already know.^[8]

Acetylcholine also plays a role in helping you maintain attention and focus while completing tasks, which enables you to learn new things.

Memory. In the short term, acetylcholine helps you hold onto information in your working memory so that you don't forget it as soon as you hear it. The neurotransmitter also helps your brain organize and code important information in your long-term memory.^[9]

One of the side effects of drugs that inhibit acetylcholine is short- and long-term memory loss.

Diseases and Disorders

Depression and bipolar disorder. People who take drugs that increase their acetylcholine levels sometimes develop symptoms of depression. This leads researchers to believe that acetylcholine plays a role in mood disorders with depressive symptoms, although the exact role isn't completely understood.^[10]

There has also been some evidence that anticholinergic drugs (drugs that reduce acetylcholine levels) ease depressive symptoms in people with major depressive disorder and bipolar disorder.

Attention Deficit Hyperactivity Disorder (ADHD). Researchers believe many symptoms of ADHD, especially those related to sensory gating and executive functioning, could be related to disturbances in the cholinergic system. For whatever reason, the receptors that normally receive acetylcholine don't function properly. As a result, acetylcholine can't carry out its sensory gating function.^[11]

Those receptors do respond to nicotine (they're technically called "nicotinic receptors"), and nicotine provides short-term relief from sensory gating and executive functioning deficits. This relationship could explain the relatively high levels of cigarette smoking among adults with ADHD.
Medication that targets acetylcholine receptors is especially effective for adults with ADHD.

Autism Spectrum Disorder (ASD). Studies suggest cholinergic system dysfunction could be the source of many behavior-related symptoms of ASD, including sensory gating deficiency and difficulty adapting to new demands or information ("cognitive rigidity"). Increasing available acetylcholine can help increase flexibility and social attention in autistic people.^[12]

Stimulating acetylcholine receptors can also improve executive functioning, planning, and organization problems.

Alzheimer's disease and dementia. People with Alzheimer's disease and dementia typically also have less acetylcholine in their brain. This deficiency leads to difficulty forming and recalling memories. ^[13]

An acetylcholine deficiency in the brain can also cause delusions and confusion, both of which often occur in people with Alzheimer's disease or dementia.

Parkinson's disease. While the motor control symptoms of Parkinson's disease likely stem from a dopamine imbalance, the cholinergic system also plays a role. Researchers theorize that dopamine and acetylcholine balance each other out to provide normal motor control, but that Parkinson's disease shifts that balance towards acetylcholine.^[14]

Studies have shown that stimulation of acetylcholine receptors improves motor control symptoms of patients with Parkinson's disease, but there is still more research to be done to understand how the dopamine and acetylcholine systems work together.

Myasthenia gravis. This disease is a chronic autoimmune and neuromuscular disease characterized by muscle weakness that gets worse after periods of activity. Muscles involved are typically the ones that control eye and eyelid movement, facial expression, chewing, talking, and swallowing. But larger muscle groups can be involved as well.[15]

Because acetylcholine stimulates movement in these muscles, increasing overall acetylcholine levels helps people with this disease regain control of their muscles and increase their muscle strength.

Lambert-Eaton myasthenic syndrome (LEMS). This autoimmune disease occurs at the neuromuscular junction and interferes with acetylcholine's ability to control muscle movement. Because the condition results in a reduced release of acetylcholine, normal muscle contractions aren't possible.^[16]

People with LEMS experience weakness in their muscles because of the decreased muscle contractions.
The upper legs and hips are typically the most affected, which leads to difficulty walking. Weakness in the upper arms and shoulders can also occur and makes self-care difficult.

Schizophrenia. Low acetylcholine levels in the brain play a role in a number of schizophrenia's symptoms, including a sensory gating deficit and visual or auditory hallucinations. Researchers speculate that increasing available acetylcholine in the brain might assist in alleviating these symptoms.^[17]

Nicotine mimics acetylcholine and triggers the same receptors as the neurotransmitter. Researchers speculate that this accounts for the higher level of smoking among people with schizophrenia—80% of individuals diagnosed with schizophrenia smoke up to 30 cigarettes a day, which is likely a method of self-medication.^[18]

Medications Targeting Acetylcholine

Antihistamines. Both prescription and over-the-counter (OTC) antihistamines, typically used to treat allergies, have an anticholinergic effect—meaning they decrease your acetylcholine levels. If you only take antihistamines periodically for a few days at a time, you don't really have anything to worry about. But taking these medications consistently over a long term can increase your risk of dementia later on in life.^[19]

A study published in 2022 was the first to include OTC antihistamines, such as Benadryl, and confirm that they carry this risk as well. The risk is especially high for older adults since acetylcholine production diminishes as you age.
Not surprisingly, short-term side effects of antihistamines include confusion, drowsiness, dry mouth, urine retention, constipation, and problems with short-term memory. These are all functions acetylcholine helps control.

Tricyclic antidepressants. Like antihistamines, tricyclic antidepressants can decrease the amount of available acetylcholine in your system.^[20] These medications are most commonly used to treat and manage major depressive disorder.^[21]

Tricyclic antidepressants, such as amoxapine and doxepin, were the first commercially available antidepressants.
Side effects of these medications related to acetylcholine include dry mouth, constipation, urine retention, drowsiness, and blurred vision. Because there are newer antidepressants on the market with fewer side effects, tricyclics are seldom prescribed.

Cholinergic medications. This type of medication stimulates receptors to better receive acetylcholine, enhancing memory, planning, time management, and organizational skills. Originally developed to treat Alzheimer's disease, dementia, schizophrenia, and autism, these drugs have also been successfully used to treat ADHD.^[22]

Common cholinergic medications include galantamine (Reminyl) and donepezil (Aricept).
Side effects include sleep disturbance, agitation, and gastrointestinal issues.

Anticholinergic medications. These medications decrease the amount of available acetylcholine in your system. Many of these drugs can treat conditions like respiratory disorders, Parkinson's disease, cardiovascular disease, urge incontinence, and psychiatric disorders.^[23]

Examples of anticholinergic medications include scopolamine, which is used to prevent nausea and vomiting, and diphenhydramine, which is used as a sleeping aid.
Botulinum toxin (BOTOX) also prevents the release of acetylcholine, which in turn prevents movement. This is why it's injected to help prevent and reduce the appearance of facial wrinkles.^[24]
Side effects of these medications include reduced saliva and tear production, constipation, urinary retention, blurred vision, flushing, and diminished muscle contraction.

Acetylcholinesterase inhibitors. Acetylcholinesterase is an enzyme that assists in the normal breakdown of acetylcholine. By inhibiting the function of acetylcholinesterase, these drugs increase the total amount of acetylcholine in your system. These drugs are most frequently prescribed to treat Alzheimer's disease and dementia.^[25]

Researchers are studying the potential for these drugs to improve cognitive function for people with schizophrenia, bipolar disorder, major depressive disorder, and other mental disorders that affect executive functioning.
Common acetylcholinesterase inhibitors include donepezil (Aricept) and galantamine (Reminyl).
Increased sweat, saliva, and tears may occur with acetylcholinesterase inhibitors. Other side effects include slow heart rate, constriction of the airways, and constriction of the pupils in the eyes.

Symptoms of Acetylcholine Deficiency

Doctors use this mnemonic to recall the symptoms of acetylcholine deficiency, also referred to as "anticholinergic toxicity." This condition typically occurs as a result of excessive dosage of anticholinergic medications.^[26]

Red as a beet. Low acetylcholine levels typically result in flushed and inflamed skin, particularly on your face. Your skin might also feel warm to the touch, particularly if you are feverish (which is another symptom of acetylcholine deficiency).^[27]

Dry as a bone. Since acetylcholine triggers the release of sweat and saliva, a deficiency of the neurotransmitter commonly results in a dry mouth and throat. You'll also feel the inability to sweat, even if you're running a fever.^[28]

Blind as a bat. Acetylcholine helps your eyes focus and dilates your pupils in response to light. If you don't have enough acetylcholine, you'll experience blurred vision and increased sensitivity to light.^[29]

Mad as a hatter. Significantly low levels of acetylcholine can render you delirious and agitated.^[30]You might also experience visual hallucinations and use rapid, staccato speech.^[31]

Hot as a hare. Fever typically accompanies low acetylcholine levels. This is one of the most common symptoms and is often present even in cases of mild anticholinergic toxicity.^[32]

Full as a flask. Because of acetylcholine's role in triggering smooth muscle contractions, if you have an acetylcholine deficiency you'll find it difficult to urinate. You might also experience constipation.^[33]

Boosting Acetylcholine Levels

Drink caffeinated coffee or tea to increase the release of acetylcholine. Caffeine increases cholinergic activity in your brain as well as boosts your overall levels of available acetylcholine. Research shows a dose of anywhere from 3 to 30 mg/kg is effective to significantly increase acetylcholine levels.^[34]

If you don't like coffee or tea, you can also take a caffeine supplement. Capsules are available online and in most brick-and-mortar stores where nutritional supplements are sold.

Eat foods that are rich in choline. Animal-based foods such as meat, poultry, fish, dairy products, and eggs are all major sources of choline. If you have a plant-based diet, you can still get adequate choline from cruciferous vegetables, soybeans, nuts, seeds, and whole grains.^[35]

As a rule of thumb, foods that are high in fat and cholesterol tend to have a lot of choline.^[36]

Take a choline supplement. Choline supplements are available online and wherever nutritional supplements are sold. Generally, doctors recommend up to 400mg for women and 500mg for men.^[37]

If you take a choline supplement, limit your total intake to no more than 3g a day, including choline from other sources. More than that could result in high blood pressure and increase your risk of heart disease.

Try an herbal supplement that increases available acetylcholine. Always talk to your doctor before starting an herbal supplement—they can interfere with any other medications you might be taking and can also worsen some health conditions. Choose high-quality supplements and follow dosage instructions.^[38]Research shows the following herbal supplements either increase your body's production of acetylcholine or block its reabsorption so it stays in your system longer:

Gingko biloba^[39]
Huperzine A^[40]
Bacopa monnieri^[41]
Ginseng^[42]

What is cholinergic crisis?

Cholinergic crisis is a toxic condition that occurs when you have excess acetylcholine. While this can happen if you're on high-dose acetylcholinesterase inhibitors, it's more common if you are exposed to nerve gas (such as the infamous Sarin gas used in chemical warfare), pesticides, or insecticides. The condition can be life-threatening if not treated promptly. If you have reason to believe you're experiencing a cholinergic crisis, call emergency medical services immediately. Symptoms include:^[43]

Blurry vision
Nausea, vomiting, and diarrhea
Wheezing and shortness of breath
Increased sweating and salivating
Frequent and more urgent urination
Slow heart rate (fewer than 60 beats per minute)
Paralysis^[44]

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