Glutamate: The Good, Bad, And Ugly Neurotransmitter

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Key Information

Naturally occurring neurotransmitter in the brain

Primary excitatory transmitter

Involved in most neurological processes

Primarily works through the NMDA and AMPA receptors

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Glutamate – An Overview

The amino acid glutamate is the major excitatory neurotransmitter in the nervous system. It is one of the most common chemical messengers that nerve cells use to communicate in the brain.1Orrego F, Villanueva S.The chemical nature of the main central excitatory transmitter: a critical appraisal based upon release studies and synaptic vesicle localization Neuroscience. 1993

In fact, it accounts for over 90% of the total synaptic connections, and is involved in every major excitatory process.2<ahref=”” target=”_blank”Glutamate (neurotransmitter), Wikipedia. 2019

So, from the chemistry point of view, the human nervous system can largely be thought of as a glutamate transmission machine.

This makes understanding glutamate critical to understanding human cognition.3Douglas RJ, Martin KA. Mapping the matrix: the ways of neocortex Neuron. 2007

You can think of the glutamate system as the “gas pedal” of the central nervous system, keeping your brain active and moving

Glutamate is regulated by the GABA system, which acts as an inhibitory counterbalance.

Not having enough GABA to mediate the excitatory qualities of glutamate can cause significant problems. Unchecked, glutamate can build up in the brain and become neurotoxic, damaging neurons.

In this way, you can think of glutamate as the gas pedal of the brain, and GABA as the brakes.

Maintaining proper levels of glutamate and GABA is critical for a healthy brain and mental function.

What Does Glutamate Do?

Learning and Memory

Glutamate nootropic
Glutamate is a critical factor in memory processes

Glutamate and NMDA receptors are heavily involved in learning and memory.

Researchers believe that plasticity occurring at glutamate synapses allows the encoding of new information.

Trials show that both sensory stimulation and learning processes induce long-term potentiation in the hippocampus.

This is critical for creating new memories.4Holtmaat A, Svoboda K. Experience-dependent structural synaptic plasticity in the mammalian brain Nat Rev Neurosci. 2009

Studies have shown that changes in strength of central glutamate synapses correlate with the processes of learning and memory, and that interfering with these changes can impair the creation of new memories.5Gerard Sanacora, Giulia Treccani, and Maurizio Popoli. Towards a glutamate hypothesis of depression Neuropharmacology. 2013


Researchers are putting more and more focus on the role of glutamate on mood as new evidence sheds light on how they are connected.

The glutamate model of mood disorders may complement the older monoamine model, which focused on neurotransmitters such as serotonin, dopamine, and norepinephrine.6Chansoo Jun, et al. Disturbance of the Glutamatergic System in Mood Disorders Exp Neurobiol. 2014

Researchers believe that disorders in the glutamate system may play a role in depression, anxiety, bipolar, and other disorders.

This is potentially due to how excessive glutamate buildup can be neurotoxic and damage neurons.

This is why several novel treatments that are being developed for mental disorders focus on the NMDA receptors, such as ketamine.7Lapidus KA, Soleimani L, Murrough JW. Novel glutamatergic drugs for the treatment of mood disorders Neuropsychiatr Dis Treat. 2013

Neurological Disease

Excess glutamate causes toxicity that can kill neurons. This can contribute to a number of neurological disorders, such as Alzheimer’s and Huntington’s Disease.8Jan Lewerenz, and Pamela Maher. Chronic Glutamate Toxicity in Neurodegenerative Diseases—What is the Evidence? Front Neurosci. 2015

So, keeping glutamate levels in check is a crucial factor in long-term brain health.

How Glutamate Works In The Brain

Glutamate is the most common neurotransmitter in your body, which means it influences virtually every process in your nervous system

Glutamate is a neurotransmitter, and like all neurotransmitters, it is synthesized inside neurons, then moved to the synaptic vesicles (the branches of the neuron).

From there, glutamate is ready to be released into the synaptic cleft between neurons.9Takamori S. VGLUTs: ‘exciting’ times for glutamatergic research? Neurosci Res. 2006

When it enters the synaptic cleft, it can bind to the receptor sites of neighboring neurons, activating them, and transmitting it’s message to those neurons.

Glutamate specifically binds to ionotropic glutamate receptors (iGluRs) at the postsynaptic membrane.

iGluRs are ligand-gated ion channels that include receptors of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, and N-methyl-D-aspartic acid (NMDA) types.10Lodge D. The history of the pharmacology and cloning of ionotropic glutamate receptors and the development of idiosyncratic nomenclature Neuropharmacology. 2009

NMDA and AMPA receptors are particularly abundant, with NMDA being the most common type of neural receptor found in the human body.

Activating NMDA receptors plays an important role in synaptic plasticity and learning. It is also the receptor that is most frequently implicated in central nervous system disease.11John W. Newcomer, e tal. NMDA receptor function, memory, and brain aging Dialogues Clin Neurosci. 200012Miyamoto E. Molecular mechanism of neuronal plasticity: induction and maintenance of long-term potentiation in the hippocampus J Pharmacol Sci. 2006

After this transmission is complete, the glutamate molecule is broken down and cleared away from the synaptic cleft to make way for future transmissions.

The “used” glutamate is taken up by astrocytes and converted to glutamine by the enzyme glutamine synthetase.

The glutamine is then released, taken up by neurons and converted to L-glutamate, and used once again for neurotransmission.13Coulter DA, Eid T. Astrocytic regulation of glutamate homeostasis in epilepsy Glia. 2012

Glutamate is also the precursor to the inhibitory neurotransmitter GABA. The enzyme glutamate decarboxylase is responsible for this conversion.

Because GABA is the counterbalance to glutamate, this process is crucial for keeping the brain in balance.14Petroff OA. GABA and glutamate in the human brain Neuroscientist. 2002

How Much Glutamate Should I Take?

Glutamate is a naturally occurring amino acid in the brain, and does not need to be taken as a supplement. You are most likely getting all the glutamate you need from your diet, as it is found in most food.

Glutamate Potential Side Effects

Glutamate is the most abundant neurotransmitter in the body and it is very necessary for proper mental functioning. However excessive levels can kill neurons and cause significant neurological issues.

Maintaining proper levels of glutamate is very important for overall brain health.

Wrapping Up

Do you have questions about, supplementing with Glutamate? Do you have experience supplementing with Glutamate? Please share your thoughts in the comments below.

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Erik Abramowitz is a certified Nutritional Therapy Practitioner (NTP), Naturopathic Doctoral student, health coach, and father. He is the primary content creator for and the host of the Holistic Nootropics Podcast.

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