Glutamate

Glutamate is the most abundant excitatory neurotransmitter in the nervous system, the chemical signal that makes a receiving neuron more likely to fire.

It is the same amino acid found in dietary protein, but the brain keeps its own supply behind the blood-brain barrier and recycles it tightly between neurons and support cells called astrocytes. Released glutamate acts on ion-channel receptors named AMPA, NMDA and kainate, and on slower metabotropic receptors. NMDA receptors in particular underlie long-term potentiation, the strengthening of synapses that supports learning and memory. Too much glutamate for too long is toxic to neurons, a process called excitotoxicity that contributes to damage after stroke and seizures.

The endocannabinoid system acts as a brake on glutamate: when a neuron fires hard, it releases 2-AG, which binds CB1 receptors on the glutamate-releasing terminal and lowers further release. CBD's relationship to glutamate is indirect and complicated, and although it is discussed in the context of the one approved cannabidiol medicine for seizures, the exact mechanism there is not settled.