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Mechanisms

BDNF & the mTOR Pathway

BDNF is often called 'fertilizer for the brain.' Ketamine acutely raises it.

Written by: Ira ZootMedical review status: Not yet clinically reviewed.Last updated: June 4, 2026Evidence: Li et al. 2010 (Science); Autry 2011

This page has been written and edited by the publisher. It has not been reviewed by a licensed clinician.

Quick answer
What is mTOR?
Mechanistic Target Of Rapamycin — a master regulator of protein synthesis. Ketamine activates mTOR signaling in cortical neurons, which builds the proteins needed to form new synapses.

The pathway

  1. AMPA receptor activation depolarizes neurons.
  2. BDNF is rapidly released from synaptic vesicles.
  3. BDNF binds TrkB receptors, activating PI3K-Akt-mTOR signaling.
  4. mTOR triggers synthesis of GluR1, PSD-95, and synapsin — synaptic structural proteins.
  5. 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.

About the author

Publisher and editor of Ketalux, based in Chicago, Illinois. Ira is a ketamine therapy patient, not a clinician. This is editorial review, not medical review: Ira is not a licensed clinician and does not provide diagnosis or medical care. Ketalux does not accept compensation from providers in exchange for favorable editorial coverage, evidence ratings, recommendations, patient referrals, or organic provider ranking. Read the full publisher disclosure →

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.