Research, practical guides, and the questions that matter to you.
Inside the science
What does ketamine block?
The NMDA receptor’s ion channel.
Outside the cell
Inside the cell
Channel openThe blue ions pass through; glutamate is a separate binding signal.
Outside the cell
Inside the cell
Channel blockedGlutamate can remain bound while the pore is blocked.
1
Glutamate
2
NMDA receptor
3
Ketamine
4
Ions
5
Cell membrane
This activated-channel model omits co-agonists, voltage-dependent gating, and other binding sites. It is not the full antidepressant mechanism, which remains uncertain.
Motion is off under your reduced-motion preference.
Nerve cells and activityDashed links mean coordinated signals.
03Dendritic spines
Small protrusions that can receive synaptic inputsLocations and numbers are explanatory, not study data.
Existing spine
Prior loss site
New spine, later
The branch shows the later state. The study sequence is described below.
Before ketamine
After the stress model
Repeated corticosterone exposure was associated with spine loss on the imaged prefrontal nerve-cell branches.
About 3 hours
Activity changed first
Circuit activity and selected behavioral effects changed before a significant increase in spine formation was detected.
12–24 hours
More spines formed later
Spine formation increased. Some spines appeared near previously lost sites; others formed at new sites. The original pattern was only partly restored.
Human resting-state fMRI · schematic locations
Front
LeftRight
Back
A Right lateral prefrontal cortex
B Left cerebellum
Broad anatomical cues, not exact clusters, a brain scan, or a new-fiber map.
18 patients · baseline and 24 hours after one infusion
Imaging tracks coordinated signals.
A · Right lateral prefrontal cortex
The paired analysis found increased global connectivity in a right lateral prefrontal cluster after ketamine.
B · Left cerebellum
Global connectivity decreased in two left cerebellar clusters. The findings were not a uniform increase throughout the brain.
Relationships between signals
Functional connectivity measures statistical relationships between MRI signals over time. The dashed lines are explanatory, not measured new fibers or counted synapses.
This small before-and-after analysis had no placebo-infusion group. It does not establish that new synapses grew or that the imaging change caused improvement.
Measured changes in depressionOne randomized trial
Adjusted difference in depression severity at 24 hours
7.95points lower with ketamine 95% confidence interval: 3.20 to 12.71
Difference in MADRS points (midazolam − ketamine)
Clinical response at 24 hours
Ketamine64%
Midazolam28%
Response: at least a 50% reduction from baseline on the MADRS depression-rating scale.
Reported study results, not a prediction of your response.
Human trial · 2013 · 73 people randomized
Improved mood must be measured in people.
In this trial of treatment-resistant major depression, a single IV ketamine infusion was compared with midazolam, an active control. The primary outcome was depression severity at 24 hours.
Biological mechanisms and symptom improvement are different kinds of evidence. A change in brain signaling alone cannot tell us whether someone feels better, for how long, or with what adverse effects.
One trial does not establish the best treatment for an individual, long-term benefit, or the effects of every formulation and route.
These trials studied esketamine nasal spray in treatment-resistant depression. They answer different questions from the single-infusion IV ketamine trial above.
TRANSFORM-2 · 227 randomized · day 28
Added to a new oral antidepressant
Esketamine + a newly started oral antidepressant, compared with placebo nasal spray + a newly started oral antidepressant.
Esketamine nasal spray versus extended-release quetiapine. Both groups continued an SSRI or SNRI antidepressant.
Esketamine + SSRI/SNRI27.1%
Quetiapine XR + SSRI/SNRI17.6%
9.5 percentage points more reached remission with esketamine at week 8. Remission meant a MADRS score of 10 or less.
Open-label treatment with blinded outcome raters; both options were add-on treatments. Quetiapine is an antipsychotic used to augment depression treatment.
Both trials were industry-funded. These results do not rank all antidepressants or establish the best option for you. Formulation, treatment history, follow-up, side effects, and treatment burden matter.
Explore ketamine for depression
A clearer place to start.
From the science to the practical details, explore what you want to understand.
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Latest ketamine research
New studies on ketamine and depression: findings, limitations and what the results mean.
A result in mice is not a result in people. A promising study is not a guarantee of benefit. The details matter: who was studied, which treatment was used, and what was actually measured.
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