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What is the mechanism of Ketamine's rapid-onset antidepressant effect?


Ketamine + MDD

The surprising discovery of ketamine’s rapid-onset antidepressant effect is a game-changer for the understanding and treatment of depressive illness, particularly major depressive disorder (MDD). The mechanism of action of ketamine’s rapid antidepressant effect is complex and still not fully understood, though it is known to modulate glutamate levels as an NMDA receptor antagonist.

About the research

As discussed in this comprehensive review, MDD is associated with decreased synaptic connectivity in the prefrontal cortex and hippocampus, along with increased synaptic activity in the amygdala and nucleus accumbens.

Decreased synaptic activity is hypothesized to result from abnormally high and sustained levels of glutamate throughout the brain, therefore explaining how ketamine’s ability to lower glutamate levels contributes to its antidepressant effects.

This paper dives deep into the specifics of neuronal function involving NMDA receptors and glutamate, which sheds some light onto the immense potential that ketamine and similar NMDA antagonists hold in the treatment of MDD.

Read the paper