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The Ultimate Guide to Neurotransmitter Modulation

Neurotransmitters are the chemicals in our brains that enable communication between neurons. Neurons are nerve cells that form elaborate networks in our brains through which nerve impulses—electrochemical signals—travel. Each neuron has as many as 15,000 connections with neighboring neurons, and interact with others across small gaps called synapses; neurotransmitters are what transmit the nerve impulses across these synapses.

Neurotransmitters have an extensive number of different mechanisms, but each acts through just one of two basic methods: excitation or inhibition. That is, they either increase the likelihood that a nerve cell will produce an impulse, or decrease it.

The only direct activity of a given neurotransmitter is to activate receptors at synapses. Thus, the effects of neurotransmitter systems depend entirely on the connections of the neurons that use that particular neurotransmitter. There are four main neurotransmitter systems that we will discuss in this article. They are:

GABA (gamma-Aminobutyric acid)

GABA is the main inhibitory neurotransmitter in humans. It reduces neuron excitation in most areas of the central nervous system, and blocks impulses between nerve cells in the brain. Low levels of GABA can be associated with anxiety disorders, attention deficit hyperactive disorder (ADHD) and epilepsy.


Dopamine plays a major role in arousal, motivation, positive reinforcement and reward perception. Drugs such as cocaine and amphetamine work by temporarily increasing the release of dopamine in the brain. Low levels of dopamine can be associated with depression, addiction and lack of motivation.


Acetylcholine is the neurotransmitter that generates alertness upon waking. It also regulates our attention, learning ability and memory. The memory deficits caused by various diseases including Alzheimer's are associated with damage to the acetylcholine production system in the brain.


Serotonin is a monoamine neurotransmitter found primarily in the intestines. In the nervous system it functions as a regulator of appetite, sleep and mood. It is considered to be the chief donor of happiness and feelings of well-being, and is modulated by several types of pharmacological antidepressants.

The Biosynthesis of Neurotransmitters

Neurotransmitters are synthesised endogenously (within the body) from precursor amino acids and other nutrients. These amino acids are essential to our health and cannot be produced directly by the body. Thus, if your diet is deficient in the amino acids required to synthesise a given neurotransmitter, then you're going to be deficient in the neurotransmitter as well.

The four major neurotransmitters are synthesised as follows:

GABA is synthesised in the brain from glutamate using the enzyme glutamate decarboxylase (GAD). Glutamate is in turn synthesised from the essential amino acid L-glutamine.

Dopamine is synthesised in the brain from L-DOPA using the enzyme aromatic amino acid decarboxylase, which is synthesised from the non essential amino acid L-tyrosine using the enzyme tyrosine hydroxylase. L-tyrosine is in turn made from the essential amino acid L-phenylalanine using the enzyme phenylalanine hydroxylase.

Acetylcholine is synthesized in the brain from the vitamin choline using the enzyme choline acetyltransferase.

Serotonin is synthesized in the brain from 5-HTP (5-Hydroxytryptamine) using the enzyme aromatic amino acid decarboxylase, which is synthesized from the essential amino acid L-tryptophan using the enzyme tryptophan hydroxylase.

Increasing Neurotransmitter Production Increasing your intake of neurotransmitter precursors is one way to increase levels of neurotransmitters, but many of these conversions also require co-factors such as pyridoxal phosphate (the active form of vitamin B6), folate (vitamin B9), methycobalamin (vitamin B12) and S-Adenosyl methionine (SAMe). These co-factors are just as important in the biosynthesis of neurotransmitters as the precursors. There's no point over supplementing with amino acids if your body can't convert them into the respective neurotransmitters.


Vitamin B5 (Pantothenic Acid) is required for the production of red blood cells, and for converting the nutrients in food into energy; but it is also essential for converting choline into acetylcholine. Vitamin B5 synthesises coenzyme-A, which is required for the acetylation of choline (it is the other precursor of acetylcholine, along with choline). Vitamin B6 is a very important nutrient that is a cofactor in the biosynthesis of serotonin, dopamine, epinephrine, norepinephrine, GABA and histamine. There are various forms of B6, but the only active form is Pyridoxal 5'-phosphate (PLP / P-5-P). Other forms, such as pyridoxine hydrochloride, are easily converted into P-5-P if you have adequate amounts of vitamin B2 (niacin)!

Vitamin B9 (Folate) and Vitamin B12 (Methylcobalamin) are important for the methylation process and in the production of various neurotransmitters such as serotonin and melatonin. Together these compounds aid in the production of S-Adenosyl methionine (SAMe), which is our bodies principal methyl donor. Vitamin C (Ascorbic Acid) is an essential cofactor for the conversion of norepinephrine (another important neurotransmitter that is involved in alertness, arousal and focus) from dopamine.

The biosynthesis of neurotransmitters can quite simply be increased by increasing intake of their respective precursors and co-factors. However, there are various other methods to increasing their endogenous concentrations, and this included the use of agonists, neuromodulators, re-uptake inhibitors and other metabolic inhibitors.

Receptor Agonists

An agonist is a chemical that binds to a respective neurotransmitter receptor, instigating it to produce a response.

All neurotransmitters are ipso facto agonists for their own receptors. That is, serotonin is an agonist for serotonin receptors. But there are also many exogenous agonists that come in the forms herbs, common foods, and pharmaceutical drugs. As an example, morphine is a full agonist at our μ-opioid receptors; it mimics our endogenous endorphins. Most natural agonists are only partial agonists, however, showing only partial efficacy at a given receptor.

Each neurotransmitter system can have any number of exogenous compounds which can act as receptor agonists. Many of the more potent ones are pharmaceutical and sometimes recreational drugs, but there are also some natural, more subtle, and safe agonists found in various herbs and plants that have enjoyed a long history of traditional use. The majority of these are agonists at GABA receptors.

Taurine is an organic compound found in animal tissues, which is a common ingredient of energy drinks has been shown to act as a GABA receptor agonist, producing anxiolytic effects.

Valerian root contains an alkaloid called valerenic acid, which is a GABA analogue and agonist.

Passion flower contains a flavinoid called chrysin, which is an agonist at the GABA-benzodiazepine receptor.

Other GABA receptor agonists include ethanol (alcohol) and kavalactone (found in kava).

There is, however, one extremely effective agonist of acetylcholine receptors, and this is nicotine. In fact, we even call a class of acetylcholine receptors the nicotinic acetylcholine receptors.


Upregulation is the increase in the number of receptors, or receptor density, to a neurotransmitter, which increases the neuron's sensitivity to that neurotransmitter. Upregulation can drastically increase the effectiveness of neurotransmitters, but is complicated. While many compounds that antagonise (block) receptors cause receptor density to increase, this effect is temporary and many come with side effects. There are really just three true, effective and long-term neurotransmitter upregulators, and they are diet, exercise (and rest), and meaningful experiences! These practices are as important as any supplement and should always be taken seriously!

Enzyme Inhibitors

Enzyme inhibitors are molecules that bind to an enzyme and decrease its activity. Since enzymes are responsible for the metabolism of neurotransmitters, enzyme inhibitors can slow the rate at which our neurotransmitters and broken down and converted.

GABA transaminase inhibitors slow the metabolism of GABA; an example is lemon balm.

Monoamine oxidase B inhibitors slow the metabolism of dopamine and tryptamine; examples include liquorice root and ginkgo biloba.

Monoamine oxidase A inhibitors slow the metabolism of serotonin, melatonin, dopamine and tryptamine; examples include the harmala alkaloids and curcumin (turmeric extract).

Acetylcholinesterase inhibitors slow the metabolism of acetylcholine; examples include huperzine A and caffeine.


In summary, there are many different methods of increasing the effectiveness of neurotransmitter systems. Above all, any supplementation should not be taken as an alternative to a healthy lifestyle. The most effective treatment will always be your diet as a whole. Healthy fats and lots of vegetables will provide your body with what it needs to keep your neurochemistry well, but sugar, too much caffeine and artificial food products will have exactly the opposite effect.

Supplementation is then necessary for all those who have an active deficiency, or those wishing to boost any one of their neurotransmitter systems to even greater levels. They can have a truly transformative impact on your focus, mood, concentration and memory when taken correctly, and can elevate levels of energy and mental sharpness to entirely new levels. Soul Juice currently offer the only complete range of neurotransmitter targeted nootropic cognitive enhancing supplements. Each product uses entirely natural products to target one specific neurotransmitter system, to maximise the benefits associated with each. Thanks for reading! Please leave any feedback in the comments section below!


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