Category: Neurotransmitters

Acetylcholine deficiency – Fight it with Nootropics

Acetylcholine, chemically, is an organic molecule (molecule containing a carbon-carbon or carbon-hydrogen bond). Its function is to behave like a neurotransmitter among humans and other living organisms. Neurotransmitters are chemicals produced inside the body that aid in transmitting electric signals from a neuron or a nerve ending to another target cell across a junction, known as synapse. The structure of the acetylcholine molecule includes an ester linkage between choline and acetic acid and is chemically represented as CH3COO (CH2)2N (CH3)3.

We hear much about vitamins and minerals, but very little about these important phospholipids, including acetylcholine.

Acetylcholine molecules are packaged inside synaptic membrane enclosed vesicles at a nerve ending, from where the molecules are ejected into the synaptic cleft. Acetylcholine molecules then diffuse across the cleft and bind to receptors in the membrane of the target post synaptic cell or neuron. This way signals and triggers are transmitted to render different bodily functions.

Acetylcholine has a crucial role in the central and peripheral nervous systems. It is also the primary transmitter to connect muscles to motor nerves via the neuromuscular junction. Acetylcholine is responsible for cognitive functioning, like memory formation, and muscle movement, coordination and communication by triggering muscle contraction as ordered by the brain. Hyperactivity or hypo-activity of the neurotransmitter can lead to problems and deter proper functioning of the body. To regulate the levels of acetylcholine, our body produces an enzyme called acetlycholinesterase.

This enzyme breaks down acetylcholine to recycle it and stop the electric signals. To further make sure that the levels of acetylcholine do not deplete, inhibitors are present that inhibit the action of acetlycholinesterase temporarily. The entire system is complex and concentration levels of all chemicals need to balanced and regulated carefully. In case there is an irregularity, it can lead to low levels of acetylcholine in the brain. Also, with age, levels of acetylcholine tend to decrease.

Unfortunately, according to a published report titled the National Health and Nutrition Examination Survey (NHANES) covering the period of 2003 and 2004, only about 10% of the population has a diet with sufficient amount of choline.  In other words, at least 90% of the population has a diet deficient in choline.  This deficiency is highest among older children, men, women, and particularly pregnant women.  The same survey also found that health care professionals are unlikely to recommend choline to patients or to recognize a deficiency.  Indeed only 6% of OB/GYNs surveyed were likely to recommend increased choline intake to pregnant women or women intending to become pregnant.

Acetylcholine deficiency can have devastating effects on the body. Patients face trouble with forming and retrieving memories. They forget faces, names, and other crucial information. They have a poor span of focus and cannot concentrate even for short period of times.  Their thoughts tend to jumble up and patients remain confused most of the times. Patients show uncontrolled muscle movements and often tremors pass through their bodies. In severe cases, acetylcholine deficiency can lead to dementia, Alzheimer’s disease and myasthenia gravis, a muscular disease.  In addition, liver function shows decline in people with a deficiency in acetylcholine and insufficient choline intake in their diets.

courtesy of

Thus, it is imperative that proper levels of acetylcholine are maintained. Dietary sources are one way to do that. Egg yolks are a major source of precursors needed for the formation of acetylcholine molecule.  A web site by the name of has very good information on the choline properties of foods, including the graphic shown.

While it is preferred to get adequate choline intake from dietary sources, this is not always possible. Nootropic supplements are another way to boost up acetylcholine. They rapidly increase the neurotransmitter’s levels and lead to improved memory and better concentration.

One of the most bio-available forms of nootropic choline is Alpha GPC. L-Alpha glycerylphosphorylcholine or choline alfoscerate, as it is also known is a naturally occuring nootropic that possesses stand alone nootropic benefits as well as being a powerful synergizing compound. It is also found endogenously in our body in small amounts and is manufactured as an extract, a highly purified form of soy lecithin. Lecithin is the brain building nutrient found in eggs, dairy, meat and wheat germ).  Alpha GPC is an intermediate form of acetylcholine, a vital neurotransmitter that is responsible for learning, memory and movement related tasks.

Choline bitartrate is pure choline in a salt form that can be absorbed in the intestines with limited problems. Alpha GPC is also a precursor to choline that goes through several changes in the intestines and while crossing the blood-brain-barrier.  It is not as good at converting to acetylcholine, which should be the goal for any nootropic supplement used as a cholinergic.

Citicoline is also a choline source that, unlike choline bitartate or other choline supplements lower on the food chain, has stand alone nootropic benefits.  In addition to providing the choline support your brain craves, it also has some dopaminergic activity to help with mood and memory. Citicoline is a precursor to both choline and dopamine so increased energy, productivity, motivation and focus may accompany increased levels of dopamine which is the pleasure, wakefulness and reward-feedback neurotransmitter. Dopamine spills out when you feel accomplished or do something you enjoy or love.

Reversible acetylcholinesterase inhibitors, obtained from plants, are extracted and purified as yet another method to obtain the nootropic supplements. Huperzine A is one of them. It is obtained from Chinese moss and is part of many nootropic stacks, including Alpha Brain. Another nootropic supplement extracted from different species of flowering plants is galantamine. It is a powerful nootropic used to treat Alzheimer’s disease but has to be used cautiously and in small amounts.

The usage and dosage of nootropic supplements to treat acetylcholine deficiency are only to be assigned by a medical professional. Great care has to taken when consuming the supplements. If they are taken without consulting a doctor, acetlycholinesterase can be inhibited for long periods of time, leading to a whole set of new problems. Some negative side effects have shown in numerous patients. They include nausea, restlessness, and vomiting and decreased heart rate in some. So it is advisable that people with heart conditions and epilepsy avoid using Huperzine A and galantamine.

Acetylcholine and Cognitive Function

Many of us have probably never heard of acetylcholine or perhaps have only heard about it on the context of Myasthenia Gravis and Alzheimer’s Disease. But do you know how important acetylcholine is, especially for an individual’s cognitive function?

What is Acetylcholine?

Acetylcholine is a common neurotransmitter and most predominant in the peripheral nervous system. Often referred to as Ach, it can be found in both the peripheral nervous system and the central nervous systems.

ACh, or Acetylcholine is an ester composed of acetic acid and choline. It serves as the transmitter or neurotransmitter at many nerve, neural, motor and synapses end plate. When an impulse arrives at the ending of the nerve, it releases the acetylcholine which is stored at vesicles at the nerve ending and it then goes to the end-plate membrane or postsynaptic membrane of the muscle fibre where it combines with a receptor molecule. This causes a change in the membrane and can generate various results. When successive nerve impulses build up, it can cause a specific action such as creating movement or building a memory.

Because acetylcholine needs to be produced in adequate amounts, has to be released from pre-synaptic vesicles and have to combine with receptors in the post synaptic membrane for it to perform many of its functions, any disruption in ACh’s production, secretion, and transmission can cause very obvious impairments to the functions associated with it.


Acetylcholine’s Discovery

1914 is a great year for neurological science, for it was the year that acetylcholine was first identified by Henry Hallet Dale. Later on, the existence of this neurotransmitter was confirmed by Otto Loewi. Both scientists received the Nobel Prize for Medicine/Physiology in 1936 for the discovery of the first neurotransmitter to be identified.

What are the Functions of Acetylcholine?

Acetylcholine functions as a neuromodulator in both the central nervous system and the peripheral nervous system. It means that it acts on different neurons all over the nervous system.

Acetylcholine plays a vital role as a part of the neurotransmitter system in the central nervous system, which is comprised of the brain and the spinal cord. Its main role is centered in arousal and attention; giving rise to the fact that it does play a very special role in cognitive function. For the peripheral nervous system, ACh plays a major part in activation of muscles as a part of its effects on the autonomic nervous system.

Because acetylcholine is in the central nervous system, a severe decrease or increase of it can affect one’s ability to get aroused and to focus. This is because ACh in the brain’s cortex acts to make the person more responsive to sensory stimuli. It has also been found that somatosensory stimulation can increase the firing rate of neurons, meaning, ACh aids in the transmission of sensory stimuli or information from the thalamus to certain regions of the brain.

In Alzheimer’s Disease, there is a decrease in the concentrations of acetylcholine in the caudate nucleus and the cerebral cortex. The disease is characterized by progressive dementia or memory loss. We can clearly see that in here, the decrease in acetylcholine has resulted in a significant impairment of cognitive function.

Arjan Blokjan published an article in a science journal which claims that acetylcholine is the neurotransmitter of learning and memory, but has this been proven? It does appear so. In an animal study published in the American Journal of Clinical Nutrition, permanent enhancement of spatial memory abilities and attention occurred in the offspring of mothers who are given prenatal choline supplementation whereas those who were restricted choline in their diet gave birth to offspring with impaired cognitive function. Since choline is one of the precursors of acetylcholine, we can derive from this study what the effect of acetylcholine is in learning and memory.

Substances that Affect Levels and Functions of Acetylcholine

In the body, there are two primary groups of substances that affect acetylcholine, cholinesterase and the anticholinesterase. From the term itself, anticholinesterase is inhibitory to acetylcholine, and cholinesterase is pro-acetylcholine. Same with cholinergic substances and anticholinergic substances. Anticholinergic substances and medications causes a decrease in the levels of choline, and can likewise decrease the level of ACh. On the other hand, cholinergic substances and medications causes an increase in the levels of choline, a precursor of acetylcholine and thus can increase its level.

An example of a group of substances that affect acetylcholine are racetams, which either increase the uptake of choline or positively modulate the signal at the acetylcholine receptors. Feel free to look more into racetams to discover their own unique and individual mechanisms. Racetams do not create more acetylcholine and actually cause an increased demand for free ACh in many cases. This is why many people will combine racetams and choline precursors together.


Dopamine and Nootropics-The Good and the Not-So-Good

When talking about nootropics, it’s simply impossible to miss the mention of acetylcholine or the cholinergic system. In fact, most nootropics specifically target the cholinergic system and glutamatergic system to enhance cognitive function while reducing the risk of side effects, tolerance as well as dependence.

Just like acetylcholine, dopamine is yet another nootropic neurotransmitter that plays an important role in cognitive function. There are many different types of supplements that help in activating and modulating dopamine along with its receptors to enhance memory. Moreover, dopamine supplements tend to improve learning as well as focus.

dopamine function on brain

How Is Dopamine Associated With Addiction?

Dopamine is considered extremely important to perform different types of cognitive tasks. In fact, it is usually called the “reward” neurotransmitter because it lets people enjoy things by getting reward through stimuli. And this perfectly explains why, dopamine is known for its strong and sought-after effects. But, at the same time, this reward system also makes dopamine a potential target for addiction. This means, any substance with a high affinity with your dopamine system has greater chances of becoming addictive.

Dopamine and ADHD-The Idea of “Smart Drugs”

Many ADHD patients seek the help of nootropics such as racetams to avoid the many side effects as well as health risks associated with ADHD drugs. Studies have shown that nootropics like Piracetam, which target the cholinergic system, may benefit people suffering from ADHD. However, it is important to note that this switch from ADHD drugs to racetams can’t solve the problem permanently. The simple reason behind this is the fact that ADHD isn’t a malfunction in the cholinergic system but it actually affects the dopaminergic system.

It is generally believed that people experiencing the condition have low dopaminergic activity. Many stimulant drugs such as amphetamines can help in strengthening dopamine activity in the brain, thereby reducing or alleviating ADHD effects. On the contrary, amphetamines also serve as powerful stimulants for people who don’t suffer from this condition. You may have heard college students trying to use these drugs to enhance productivity, which is what gives them their popular name i.e. smart drugs.

It’s important to understand that the main difference between smart drugs and nootropics is that the latter carry reduced addiction risks. This is why; dopamine-enhancing drugs don’t usually make it to the nootropics family. In fact, most stimulants tend to increase dopamine levels, thereby enhancing particular areas of cognitive function. When using these stimulants for enhancing memory, be careful and avoid long-term use.

Two Popular Nootropics Associated with Dopamine

Mucuna Pruriens and Dopamine

Mucuna Pruriens is a herbal extract that is extremely powerful and may serve as an effective nootropic. It contains L-Dopa, which is actually a precursor to dopamine. If you have low motivation and/or libido, you may have low levels of dopamine. And by using this herb as a nootropic, you can increase your dopamine levels. Even if you have normal dopamine levels, increasing L-dopa can still help with cognition.

Sulbutiamine and Dopamine

Sulbutiamine is a synthetic vitamin derivative that carries mild stimulating effects. This substance has a different method of action than typical ampakines and racetams. The primary method of action of sulbutiamine is believed to be party involved with dopamine. The supplement enhances the density of dopamine receptors, known as D1 and D2. Although it is safer than typical “smart drugs”, this supplement may have some form of addictive potential. Tolerance buildup is yet another effect associated with sulbutiamine use.

Acetylcholinesterase Inhibiting Nootropics & Their Benefits

Acetylcholinersterase is an enzyme that breaks down acetylcholine within the brain. Acetylcholine is the target neurotransmitter of many nootropic supplements. Having higher than normal levels of acetylcholinesterase may have negative effects on the cholinergic system and cognitive functioning in general.

Acetylcholine & Acetylcholinesterase Relationship

Acetylcholine is prominent not only in cognitive functioning, but also muscle movement, communication and coordination. It helps to trigger the contraction and movement of muscles. The neurotransmitter basically triggers your muscles to move and work in the way your brain wants to. Obviously, this process is very complex as there are different systems involved however this is the basic function of acetylcholine in brain-to-muscle communication.

Like many different enzymes in the body, acetylcholinesterase is necessary for regular human function and homeostasis in the brain. The enzyme terminates the signals from acetylcholine. Without acetylcholinesterase, our bodies would go into convulsions or paralysis because our bodies would not be able to control muscle functions from acetylcholine signals. This is why there is a natural amount of acetylcholinesterase within our brains.

Acetylcholinesterase & Acetylcholine

Types of Acetylcholinesterase Inhibitors

Acetylcholinesterase inhibitors come in two types: reversible and irreversible. Irreversible acetylcholinesterase inhibitors cannot be used safely in mammals. This is because these types terminate acetylcholine in a loop which can cause seizures, convulsions and paralysis. Reversible acetylcholinesterase inhibitors can be used safely in humans and are a target for Alzheimer’s treatments.

Reversible acetylcholinesterase inhibitors can also be used as nootropics. Many popular nootropic blends such as Alpha Brain work primarily off the function of acetylcholinesterase inhibitors. These blends need acetylcholinesterase inhibitors to synergistically activate the very small amounts of other cholinergic ingredients. This is why these supplements work well.

Many people will also include acetylcholinesterase inhibitors into their nootropic stacks. They are very synergistic and also very powerful. One needs to be careful with how the proportion a stack with acetylcholinesterase inhibitor because only a very small amount is needed to activate the acetylcholinesterase inhibiting properties. This is why this method is only utilized for experienced and advanced nootropic users.

Huperzine A

Huperzine AHuperzine A is a type of Chinese moss that has potent reversible acetylcholinesterase inhibiting properties. It can be obtained as a supplement within the United States and many other countries. Only very small amounts of huperzine A is needed to activate the acetylcholinesterase inhibiting qualities.

Huperzine A is the main acetylcholinesterase inhibiting component in the product Alpha Brain and other nootropic blends. It is very effective and synergistic with cholinergics like citicoline and alpha GPC. Huperzine A also combines well with the racetams and will produce very strong cholinergic effects when stacked together.

Huperzine A may have side effects when used alone however these will most likely manifest when used in a stack. Side effects may include: headache, nausea, gastrointestinal problems and depression amongst others.


Galantamine is another popular reversible acetylcholinesterase inhibitor that may be used as both a general nootropic and Alzheimer’s aid. It may be prescribed by a doctor or obtained over-the-counter as a supplement . Galantamine is a natural alkaloid derived from a number of flowering plants in several species.

As with huperzine A, galantamine is also a very powerful acetylcholinesterase inhibitor. It needs a very small amount to produce benefits as a nootropic. Galantamine should be used with caution and especially within a cholinergic stack. It can also produce side effects consistent with cholinergic hyper stimulation.

Acetylcholinesterase & Safety

Using reversible acetylcholinesterase inhibitors requires knowledge and care. One must use acetylcholinesterase inhibitors in the right dosages and amounts. Overall, acetylcholinesterase inhibitors can be seen as very safe when used in the right dosages and circumstances.

If you are looking to use acetylcholinesterase inhibitors in a nootropic stack with choline and racetams it is important to try both on their own first. This is because adding all three of these at once could increase the risk of side effects.

 It is thought that overloading the cholinergic system in some people can cause many negative side effects. This may not be true in all people however it seems to be a consistent problem nootropic users have. To avoid these problems always start slow and with smaller dosages. This will drastically reduce the risk of side effects.

How to Identify & Overcome Low Dopamine

Dopamine is a catecholamine neurotransmitter with many important functions. It is the primary reward neurotransmitter with many other implications on cognitive functioning and mood. Dopamine is considered a nootropic neurotransmitter due to its effects on essential cognitive functioning. Many drugs both legal and illegal use the dopamine structure, method or pathway to pharmacologically change the way our brains work.

Dopamine imbalance can cause many problems. Anhedonia (not feeling enjoyment), depression, low libido and cognitive decline may all be caused by low dopamine. The neurotransmitter not only works as a nootropic, but also as an anti-depressant and it is often overlooked as being a problem. Many people with low dopamine may be seen as being depressed and prescribed SSRI’s when in fact, these many do more harm than good (raising serotonin can lower dopamine further).

neurotransmitters: dopamine. seretonin, norepinephrine

Malfunction of dopamine signals is a main theory behind ADHD. ADHD is a very serious problem and it is often not identified soon enough. These people basically have weak dopamine signals due to their chemical makeup. Amphetmaine drugs meant to imitate and amplify dopamine effects are often an only option for these people. These drugs are effective but very unsafe and addictive.

Causes & Symptoms of Low Dopamine?

Finding a root cause for low dopamine is very tricky. There is no way to tell wether or not someone will be low in dopamine. If you do have low dopamine it is important to be mindful and aware as there may be ways to correct the problem. People with low dopamine are more likely to be depressed, have low energy, sex drive and become drug addicts or become addicted to other things (sex, gambling, adrenaline).

Understanding the ADHD mind can help us understand some of the aspects of low dopamine. To the naked eye, most ADHD suffers seem to be very happy. The reason we (non-ADHD sufferers) assume this is becaused people with ADHD often seem very lively and social. This may be true because people with ADHD may be very social and impulsive with a lack of focus.

We may observe these signs as a sign of happiness however this often couldn’t be further from the truth in fact, ADHD sufferers are often very depressed and just don’t show it. ADHD sufferers are also more likely to become addicited to substances or events that increase dopamine response (cocaine, meth, gambling, danger).

Solving Low Dopamine

The good news is that solving low dopamine can be fairly easy. The bad news is that a lot of these drug treatments are not safe. Most substances involving dopamine are stimulants that are also addictive. For safety, these types of drugs should ALWAYS be ruled out first. They are not a long-term or viable treatment option for low dopamine and having low dopamine in the first place can increase the desire for these substances even more so avoid at all costs.

Trying to increase dopamine with supplementation is a great option. There are several natural supplements to do this relatively safetly. They are not drugs so one does not need to worry about addiction or downregulation of dopamine receptors. For those with low dopamine, this should always be the first choice. The other less safer option, may be to ask for a MAO-b from your doctor.

Dopamine Precursor Nootropics

L-Phenylalanine → L-Tyrosine → L-DOPA → Dopamine

Above is the body’s route of synthesis for natural dopamine. L-Phenylalanine is an amino acid and a precursor to another amino acid, L-tyrosine. In reality, taking either of these amino acids will help to increase the level of dopamine in the brain. They also function mildly as nootropics due to this effect.

Dopamine itself cannot be orally consumed as a supplement because it cannot penetrate the brain. The next best thing to dopamine is its direct precursor, L-DOPA. L-DOPA can be obtained in pure form however it is a prescription prescribed for Parkinson’s disease in many countries. The supplement, mucuna pruriens is rich in L-DOPA and a great nootropic supplement to increase dopamine.

MAO-B Inhibitors

Monoamine oxidase B is an enzyme that breaks down dopamine. MAO-B is necessary in the body however it can be in high levels and negative for maintaining healthy levels of dopamine.

There are two groups of MAO-B inhibitors: reversible and irreversible. Reversible ones are much less effective however they are less dangerous. Irreversible MAO-B inhibitors like Selegiline are very effective for increasing dopamine however they should only be used under the supervision of a doctor.