A Guide to Neurotransmitter Balance (2022)

What is neurochemical balance?

The brain is constantly striving to keep your different neurochemical systems in balance in response to your ongoing internal and external needs - something that it does through constant neurobiological and synaptic shifts which alter the levels of different neurotransmitters.

Too much or too little of any of one neurotransmitter upsets the entire balance of the brain. This unbalancing manifests itself as changes in the way you think, feel and behave - the mental highs and lows of your daily life.

Changes in the different levels of neurotransmitters can be transient - altered by a particular event or experience that happens to you during your day, or more enduring as an ongoing neurochemical ebb and flow from morning to night, typically in line with your in-built circadian rhythm

Excitation vs. inhibition

One of the major juggling acts is between the level of excitation and inhibition in the brain, mediated by the corresponding levels of the neurotransmitters glutamate and GABA.

During the night when you need to sleep, the inhibitory neurotransmitter GABA blocks the activity of other neurotransmitter systems, shifting the balance in its favor.

In contrast, during the day when you need to think and react, the brain rebalances itself so that these other neurotransmitter systems stop being under sleep-based inhibitory control and are more free to send messages through their respective neural systems.

Consequences of neurochemical imbalance

The consequences of having a neurotransmitter imbalance depends on how extreme the imbalance is, but generally most clinical disorders involving the brain have some degree of neurotransmitter imbalance - whether that be too little of a particular neurotransmitter, or in some instances, too much.

Examples of this include dopamine depletions in Parkinson’s disease, serotonin depletions in depression, GABA depletions in anxiety, acetylcholine depletions in Alzheimer's disease and glutamate and GABA imbalance in epilepsy.

In addition, more transient fluctuations in neurotransmitters imbalance can cause changes across a wide range of behaviours including your mood, your ability to sleep properly, your attentional focus and ability to remember information, or your motivational state, to name a few.

What can affect your neurochemical balance?

Diet

Maintaining a healthy balance of neurotransmitters requires a healthy balanced diet. This provides the brain with the necessary neurochemical building blocks, as well as the appropriate chemicals which are required to support their synthesis, transportation and degradation.

This includes ensuring the brain has sufficient energy supplies (e.g. from carbohydrates and fats which ultimately help to form energy-generating ATP molecules), amino acids, and the various vitamins and minerals which are cofactors in the enzymatic pathways.

Although many of the neurotransmitters cannot easily cross the blood-brain barrier, their amino acid precursors, in some instances, can do so, providing a potential route for influencing the concentration of precursors in the brain under certain circumstances.

Although there are various foods which contain neurotransmitters and their amino acid precursors, their ability to modify the brain’s response depends on how easily they can cross the blood-brain barrier - the gateway from the body (specifically the bloodstream) into the brain. GABA and Glutamate require a significant concentration differential between the blood and brain to be allowed in.

Neurotransmitters like dopamine and serotonin cannot cross the blood-brain barrier because it does not contain the necessary “transport” mechanisms needed to get them across. In contrast, in some instances, their precursor amino acids can cross the blood brain barrier. But because the amino acids often compete against each other to determine which one gets to cross, it is the relative levels of the amino acids which is important, not just the absolute levels ingested.

Medication and Drugs

Medications and drugs can act to disrupt your brain’s neurotransmitter balance, or compensate for its imbalance.

They can act at various points of the synapse to:

  • Mimic the effects of the neurotransmitter, for example amphetamines acting on catecholamine receptors
  • Enhance the effects of the neurotransmitter, for example benzodiazepines potentiate the action of GABA receptors
  • Prevent the reuptake of neurotransmitters, as is the case with cocaine and catecholamines or Prozac and serotonin).
  • Block (Antagonize) receptors, for example the action of the beta-blocker propranolol on noradrenergic and adrenergic receptors.

Chronic Stress

Your body’s physiological stress response is mediated, in part, by the steroid hormone cortisol, released as a result of the activation of a brain-body pathway called the hypothalamic-pituitary-adrenal axis.

Your body’s physiological stress response is mediated, in part, by the steroid hormone cortisol, released as a result of the activation of a brain-body pathway called the hypothalamic-pituitary-adrenal axis.

One neurotransmitter which is particularly badly affected is glutamate, your brain’s primary excitatory neurotransmitter. Being chronically stressed causes more glutamate than normal to be released at synapses in the brain’s prefrontal regions - involved in higher-order thinking - and hippocampus - a region involved in memory.

It also interferes with how effectively glutamate is cleared away from the synapse when it is no longer required. Too much glutamate in these regions results in cognitive impairments especially in relation to the way you learn and remember.

Chronic stress also reduces the level of serotonin in the brain, in part explaining the link between chronic stress and depressive disorders.

How do we correct neurochemical imbalances?

Targeted Amino Acid Therapies

Targeted amino acid therapies are when supplements of a particular neurotransmitter are given to an individual to try and combat any perceived imbalances in the brain's neurotransmitter systems.Targeted amino acid therapies work by substantially altering the relative balance of amino acids ingested within your diet.

They are based around the finding that subtle change in dietary intake are not usually sufficient to alter levels of particular neurotransmitters in your brain because they do not go far enough to increase the concentration of a particular amino acid over and above others to allow it to preferentially cross the blood-brain barrier.

This is necessary because of the competitive interactions between amino acids trying to cross the blood brain barrier. Supplementing a particular amino acid aims to disrupt this balance to promote the uptake of that amino acid, over others, into the brain.

Exercise

It is well established that exercise is good for the health of your body. It is also good for your brain, improving the way you think and feel across a number of different metrics.

One reason for this is due to the way exercise influences your brain’s neurochemical balance by altering the levels of monoamine neurotransmitters such as serotonin, dopamine and noradrenaline. Serotonin, and to some degree dopamine, are involved in what is called “central fatigue” - the process by which your brain feels tired after strenuous or prolonged exercise.

Doing high-intensity exercise increases the availability of brain tryptophan and promotes the synthesis of serotonin which, in combination with changes in the other monoamine neurotransmitter systems, mediates the behavioural sensations of fatigue and subsequent positive changes in mood.

Light Therapy

Light therapy has also been used to try and manipulate the levels of neurotransmitters in the brain. One of the most commonly targeted systems in serotonin due to its role in depressive disorders such as Seasonal Affective Disorder.

Therapeutic interventions which artificially simulate the “lux” level of natural light have been shown to prevent a decline in mood in situations where there is an insufficient supply of tryptophan - the main precursor to serotonin.

Because of the “entraining” effect of light, it has also been used to treat disorders where there is a disruption in the natural circadian rhythm. However, the timing of the light therapy is critical to its effectiveness and has to be aligned against your in-built circadian rhythm to avoid further disruption of the natural ongoing metabolic cycles within your body and brain.

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