Mechanism

Glutamate

Main excitatory neurotransmitter of the central nervous system. Regulated through its NMDA, AMPA, and kainate receptors. In adequate amounts it is essential for learning and memory; in excess it is neurotoxic and maintains sensitization of the fear circuit in anxiety and OCD. Target of drugs such as memantine (Alzheimer's) and ketamine (treatment-resistant depression).

Effect by goal · level of evidence

Learning and memory

modulates Very high physiology (A)

Basis of learning

Long-term potentiation (LTP) mediated by NMDA receptors is the cellular basis of learning and memory.

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Neuronal excitotoxicity

harms Very high physiology (A)

Neurotoxic in excess

Acute excess (stroke, epilepsy, trauma) causes neuronal death through intracellular calcium overload. NMDA antagonists such as memantine limit damage in Alzheimer's.

Anxiety and OCD

overactive Moderate RCT (AA)

OCD target

Excess glutamate maintains sensitization of the fear circuit. NAC modulates this pathway and shows a signal in OCD (PMID 24107021).

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Treatment-resistant depression

modulates Moderate RCT (AA)

New antidepressant target

Ketamine and esketamine, rapid NMDA receptor antagonists, show a rapid antidepressant effect (hours) in treatment-resistant depression. Opposite effect to the classic SSRI.

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Information, not medical advice. Scientific evidence reflects the quality of the studies.