Latest medical review on: July 15th, 2026. Medically reviewed by Instructor in Psychiatry at Harvard Medical School and Lumin Health Co-founder, Chief Medical Officer Dr. Ben Yudkoff.
How do ketamine and esketamine (Spravato) work in the brain?
While ketamine and Spravato (esketamine) grow increasingly popular for treatment of treatment-resistant depression and major depressive disorder, the chemistry and underlying science behind ketamine treatment can often be misunderstood. Thanks to a thoughtful exploration with Dr. Ben Yudkoff — Lumin Health's Chief Medical Officer — Lumin Health has put together a thorough introductory guide to some of the core concepts.
If you are interested in learning if ketamine therapy and/or esketamine (Spravato) is right for you, don't hesitate to get in touch with our compassionate team of experts below. Esketamine (Spravato) is often covered by insurance and Lumin Health is happy to do all the paperwork on your behalf.
Insurance-covered Spravato (esketamine) treatment in Boston
Research on ketamine's impact in the brain
Ketamine's rapid antidepressant effects are driven by molecular neuroplasticity cascades — not just NMDA receptor blockade. A Systematic Review confirmed that glutamate surges activate AMPA receptors and trigger mTOR signaling, leading to rapid synaptic remodeling in brain regions linked to mood regulation.
Research increasingly shows that ketamine acts through multiple pathways simultaneously. A study on ketamine's impact on brain receptors details how AMPA receptor activation, BDNF-TrkB signaling, and mTOR pathway engagement work together to produce antidepressant effects that begin within hours of administration.
Ketamine rapidly increases brain-derived neurotrophic factor (BDNF) in the prefrontal cortex and hippocampus — regions central to mood and cognition. This study regarding BDNF release shows that this mechanism drives the formation of new synaptic connections, a key mechanism behind ketamine's sustained antidepressant effects.
Depression is associated with overactivity in the brain's default mode network (DMN), the system responsible for rumination and self-referential thought. A study on ketamine's effect on the default mode network demonstrated that ketamine reduces prefrontal DMN connectivity, which may help explain how it interrupts depressive thought loops.
Research increasingly shows that ketamine acts through multiple pathways simultaneously. A study on ketamine's impact on brain receptors details how AMPA receptor activation, BDNF-TrkB signaling, and mTOR pathway engagement work together to produce antidepressant effects that begin within hours of administration.
Ketamine rapidly increases brain-derived neurotrophic factor (BDNF) in the prefrontal cortex and hippocampus — regions central to mood and cognition. This study regarding BDNF release shows that this mechanism drives the formation of new synaptic connections, a key mechanism behind ketamine's sustained antidepressant effects.
Depression is associated with overactivity in the brain's default mode network (DMN), the system responsible for rumination and self-referential thought. A study on ketamine's effect on the default mode network demonstrated that ketamine reduces prefrontal DMN connectivity, which may help explain how it interrupts depressive thought loops.
More reading on ketamine's impact on the brain from Dr. Ben Yudkoff
Latest medical review on: July 15th, 2026. Medically reviewed by Instructor in Psychiatry at Harvard Medical School and Lumin Health Co-founder, Chief Medical Officer Dr. Ben Yudkoff.
Frequently Asked Questions
Quick answers to your most pressing questions about ketamine therapy, depression, and the neuroscience of ketamine from Lumin Health and our team of expert clinicians.
What does ketamine therapy do in the brain?
How does Spravato (esketamine) relate to ketamine treatment?
What does ketamine treatment feel like during a session?
How quickly can ketamine or Spravato work for depression?
How long do benefits from ketamine therapy last?
Who is not a good candidate for ketamine or Spravato?
Ketamine treatment led by psychiatrists at Lumin Health – decades of experience, thousands of treatments delivered.
Board-certified psychiatrists screen for medication interactions, monitor vitals, and coordinate with your existing care team.
We specialize in coordinating care for people with complex medical histories.
We specialize in coordinating care for people with complex medical histories.
The Lumin Health medical team
Our team of academically-affiliated psychiatrists and clinicians bring deep expertise to ketamine and esketamine treatment. As specialists in esketamine (Spravato) and ketamine therapy, we provide safe, effective care with rigorous protocols and personalized treatment plans.
The Lumin Health concierge team
Our patient concierge team handles the entire process: insurance verification, scheduling, and intake. Our team looks forward to connecting you to ketamine treatment and answering your questions about ketamine and Spravato. We handle the details so you can focus on getting better.
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Brookline, MA 02446Bethesda
4825 Bethesda Avenue
Suite 200
Bethesda, MD 20814
10 Langley Road, Suite 200
Newton, MA 02459Cambridge (Harvard Square)
50 Church Street, 3rd Floor
Cambridge, MA 02138Woburn
300 Tradecenter Drive, Suite 3400
Woburn, MA 01801Brookline
1101 Beacon Street, Suite 4E
Brookline, MA 02446Bethesda
4825 Bethesda Avenue
Suite 200
Bethesda, MD 20814
Monday - Friday, 8am - 6pm
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