A single dose triggers a four-stage cascade inside your brain. Receptors block, glutamate surges, signaling pathways activate, and new synaptic connections form. The result is weeks of clinical response from a few hours of treatment. Every claim below is cited to published neuroscience.
Scroll to follow the four-stage cascade from receptor binding to new synaptic connections. Each claim is anchored to published neuroscience literature.
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Stage 1 — minutes after administration
Ketamine binds non-competitively to the NMDA receptor on inhibitory interneurons. By temporarily blocking this receptor, ketamine releases the brain’s glutamate system from its usual GABA-driven brake.
Stage 2 — within the first hour
With the GABA brake released, excitatory pyramidal neurons release a brief burst of glutamate into the synaptic cleft. This surge is the first measurable downstream effect and is required for the antidepressant response.
Stage 3 — 1 to 24 hours
The released glutamate activates AMPA receptors on post-synaptic neurons. AMPA activation triggers intracellular signaling cascades (mTOR pathway) that begin the process of building new synaptic protein.
Stage 4 — 24 hours to weeks
mTOR activation drives the release of brain-derived neurotrophic factor (BDNF). BDNF promotes growth of new dendritic spines — the physical points of synaptic connection. Patients commonly report the lift in mood as these new connections stabilize.