Mechanisms
BDNF & the mTOR Pathway
BDNF is often called 'fertilizer for the brain.' Ketamine acutely raises it.
Medically reviewed by: Pending medical review(draft)Last updated: June 4, 2026Evidence: Li et al. 2010 (Science); Autry 2011
The pathway
- AMPA receptor activation depolarizes neurons.
- BDNF is rapidly released from synaptic vesicles.
- BDNF binds TrkB receptors, activating PI3K-Akt-mTOR signaling.
- mTOR triggers synthesis of GluR1, PSD-95, and synapsin — synaptic structural proteins.
- New synapses form within 1–2 hours.
Why it's chronically depressed in depression
Chronic stress reduces BDNF expression and dendritic spine density in prefrontal cortex. Ketamine appears to rapidly reverse this — at least temporarily — which is why integration matters so much for sustaining the change.
Educational use only. The content on this page is provided for general educational purposes and does not constitute medical advice, diagnosis, or treatment. Ketamine and related therapies carry risks and are appropriate only under qualified medical supervision. Always consult a licensed healthcare professional about your individual situation. Information may change as research evolves.