GABA-Glutamate - A Framework for High-Gain Nervous Systems

Introduction

For people who are above-average sensitive to certain kinds of stimulation, gaining more control over your excitation and relaxation can be useful by diving one level deeper into the bodily processes that cause them. Mechanistic theory and tested outcomes can provide useful insights, even though the body and brain are complex systems we will never understand completely. I find it useful to introduce these concepts because they add dimensionality and levers to explain and control your excitation, relaxation, and recovery.

The aim is to look at effects, approaches and interventions and explain them from the interplay of these variables. Note that the aim of these variables is not technical perfection, but get a practical grasp and more nuanced intuition of what is going on in your body. The following example demonstrates how adding one dimension can change how you look at relaxation:

Instead of considering relaxing and having too much energy on a single scale as such:

You can look at it as having both a gas and a brake pedal, which can either be high or low:

The implications of this is that you can be in a productive mood (high gas & high brake) OR you could be in a fragile state without realizing it (high gas but low brake) and get an afternoon energy crash or risk getting overstimulated.

Disclaimer

I am by no means an expert on this topic. All knowledge input for this article comes from ChatGPT 5.2 and Claude 4.5. Processes are way too simplified and even the most specialized people on these fields do not know the full interactions of these complex systems. Effects can also vary wildly per person. Use this article EDUCATIONALLY or better, paste it into an LLM yourself including your own context and use it as a tool to get to know yourself better and more technically.

Introducing Terms & Concepts

I will introduce several terms that will be used to puzzle all the variables and relationships together.

Neural gain or high gain: a high gain person’s brain amplifies signals, small inputs can create big responses.

GABA: the brain’s brake pedal and main inhibitory neurotransmitter, it reduces brain activity and promotes calm.

Glutamate: the brain’s gas pedal and main excitatory neurotransmitter, it increases the brain activity and alertness. It drives action, enables learning, focus and responsiveness.

Dopamine: neurotransmitter that signals reward and motivation. It says: “this is important, pay attention and go get it”.

Serotonin: dopamine’s counterbalance, it promotes mood stability, contentment and the feeling of “okay with what you have”. Helps stress response shut off faster.

Norepinephrine (noradrenaline): the brain’s alertness and focus chemical for stress and concentration. Increases arousal and vigilance without the full fight or flight intensity. (hypervigilance, scanning faces/cues)

Epinephrine (adrenaline): the body’s emergency hormone, can trigger fight-or-flight energy release, high heart rate and heightened senses, for both danger and excitement.

Acetylcholine: the brain’s spotlight chemical, it narrows focus and enhances clarity, learning and memory.

Histamine: the brain’s “stay awake” signal, maintains arousal and can trigger allergic and inflammatory responses in the body.

Glycine: inhibitory neurotransmitter similar to GABA, calming the nervous system and reducing neural excitability.

Oxytocin: the bonding chemical, released during social connection, touch and trust, promoting “relaxed openness”.

Vasopressin: oxytocin’s counterpart, focusing on vigilance and socially protective behavior.

Orexin (a.k.a. hypocretin): the “stay awake” signal, supporting histamine.

CRH (appendix only)

Testosterone (appendix only)

Estrogen (appendix only)

Progesterone (appendix only)

Cortisol: main stress chemical, causes both good and bad kinds of stress.

CRH: starting signal of the HPA axis.

Melatonin: the darkness signal, it tells the brain it’s time to sleep.

Endocannabinoids: the body’s self-produced molecules that dial down stress, pain and excessive neural firing.

BDNF: key driver of neuroplasticity and it repairs damage from stress or overstimulation.

Adenosine: the fatigue signal, it accumulates with tasks and during the day.

HPA axis (Hypothalamus-Pituitary-Adrenal axis): brain to body stress communicating system. When the brain senses threat, it signals the pituitary and the adrenals create cortisol.

Vagal tone: the strength of the vagus nerve’s calming influence. Higher tone = higher recovery and parasympathetic brake strength.

Glutathione: an antioxidant that is a main buffer for the brain, protects dopamine and serotonin from oxidative stress and from enhancing the stress loop.

Situation Effects

I will present these as a list and with little elaboration. Each situation will have a simple and a comprehensive version. The aim here is to get a sense of what is happening in your body and brain in each situation.

Social Overstimulation

For high-gain people, the simple cascading effect is: Social input → Glutamate ↑ → Norepinephrine ↑ → Cortisol ↑ → Vagal tone ↓ → GABA overwhelmed → Crash

Comprehensive:

Sensory Overload

Simple version: Sensory input → Glutamate ↑ → Histamine ↑ → GABA overwhelmed → Crash

Key difference from social: Histamine is more central here, it’s the “can’t tune out” signal that keeps sensory channels wide open.

High-Gain Induced Anxiety

Overstimulation induced anxiety: Overstimulation → Acetylcholine depleted → Executive control ↓ → Intrusive thoughts → Anxiety

Relaxation induced anxiety: Relaxation → Executive control ↓ → Glutamate still high → Intrusive thoughts → Anxiety

Anxiety Triggers

Fragile baseline → Trigger → Norepinephrine ↑ → Executive control fails → Anxiety loop

Depression

Simple version: Chronic stress → Glutathione ↓ → Dopamine/Serotonin destabilize → Effort feels pointless → Depression

It’s not necessarily the low dopamine and serotonin but the damaged dopamine and serotonin systems from chronic oxidative stress. The brain says “nothing is worth this cost” and the stress is hard to shut off.

Exercise - HIIT

Intense burst → Glutamate ↑↑ → Cortisol spike → Endorphins → BDNF ↑ → Sharper (if recovered) OR crash (if depleted)

Exercise - Zone 2 Training

Gentle effort → Glutamate stable → Vagal tone ↑ → GABA supported → Calm energy

Exercise - Strength Training

Controlled effort → Dopamine ↑ → Cortisol spike + recovery → BDNF ↑ → Resilience

Exercise - Chronic Effects

Consistent exercise → BDNF ↑ → Vagal tone ↑ → Glutathione capacity ↑ → Lower baseline gain → Resilience

Stress and Deadlines

Deadline pressure → Norepinephrine ↑ → Dopamine ↑ (short-term) → Cortisol ↑ sustained → Dopamine crashes → Burnout

Inflammation

Inflammation → Vagal tone ↓ → Glutamate cleanup ↓ → Brain more fragile → Easier crash

Sleep

Sleep → Glutathione replenishes → BDNF active → Adenosine clears → Glymphatic cleanup → System resets

Breathing

Slow breathing → CO₂ ↑ → Vagal tone ↑ → Acetylcholine ↑ → Inflammation ↓ + Heart rate ↓ → Calm

Morning Light Exposure

Morning light → Cortisol peaks early → Melatonin timed correctly → Stable energy curve → Less fragile by afternoon

Food Effects

Hydration

Dehydration → Cell function ↓ → Cortisol ↑ → Histamine ↑ → Lower stress tolerance

Caffeine

Caffeine → Adenosine blocked → Glutamate ↑ + Norepinephrine ↑ + Dopamine ↑ → Sharp OR overstimulated (depends on baseline)

Sugar and Carbs

Sugar → Blood glucose spike → Insulin spike → Glucose crash → Cortisol ↑ to compensate → Fragile state

Protein (and Tyrosine)

Protein → Tyrosine → Dopamine precursor available → Sustained drive (if cofactors present)

Alcohol

Alcohol → GABA ↑ + Glutamate ↓ → Rebound: Glutamate ↑ + GABA sensitivity ↓ → Lower baseline next day

Histamine

Histamine-rich food → Histamine ↑ → Arousal ↑ + Inflammation ↑ → Harder to calm down

If you already run hot (high histamine/arousal), these foods add fuel. Especially problematic in evening when you need histamine to drop for sleep.

Supplement Effects

Magnesium

Magnesium → Glutamate receptor calmed → GABA function supported → Lower gain, easier relaxation

Can be depleted by stress.

L-Theanine

L-theanine → Glutamate modulated → GABA ↑ → Calm focus without sedation

Taurine

Taurine → GABA receptor support → Glutamate buffered → Calm without drowsiness

Glycine

Glycine → Inhibitory neurotransmitter → GABA partner → Deeper sleep, calmer nervous system

Glycine is a quieter brake than GABA, works well for nighttime. Bonus: it is one of three amino acids needed to make glutathione, so it supports recovery capacity too.

Lysine (+ Arginine)

Lysine + Arginine → Serotonin receptor modulation → Cortisol response ↓ → Lower anxiety reactivity

Lysine alone blocks stress-induced anxiety via serotonin receptors, arginine alone supports blood flow and can lower blood pressure; together they reduce HPA reactivity more than either alone.

This combo targets the stress response system directly rather than GABA/glutamate. Useful if your issue is overreactive cortisol spikes rather than pure excitation.

GABA

GABA supplement → Limited brain entry → Peripheral calming → Mild effect (if any)

Supporting your own GABA production and receptor function (magnesium, glycine, taurine) is more reliable than supplementing GABA directly.

NAC

NAC → Glutathione precursor → Antioxidant capacity ↑ → Glutamate modulated → Better cleanup and recovery

Omega-3

Omega-3 → Inflammation ↓ → Cell membranes healthier → Neurotransmitter signaling improved → BDNF ↑

Omega-3 is a slow-burn intervention. It does not calm you acutely, but over weeks it lowers baseline inflammation, improves receptor function, and supports the structural integrity of your brain. Foundation layer, not rescue layer.

Non-Magnesium Electrolytes (Sodium & Potassium)

Electrolytes → Cell signaling ↑ → Neurotransmitter function ↑ → Stable energy, clearer cognition