Scientists peek inside brain to unlock Ketamine's rapid Mood-Boosting secret
NCT ID NCT06788249
First seen Jun 27, 2026 · Last updated Sep 11, 2026 · Updated 4 times
Summary
This study aims to understand how ketamine produces rapid antidepressant effects by using a special brain scan (GluCEST) to measure changes in glutamate, a key brain chemical. Ten adults with treatment-resistant depression will receive a single ketamine infusion and undergo imaging before and after. Mood changes will also be tracked. The goal is to identify the brain mechanism behind ketamine's fast action, which could lead to better, longer-lasting depression treatments.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- ketamine
- What this could lead to
- If it works, this could point toward new antidepressant drugs that work faster and last longer by targeting the same brain mechanism.
- What could go wrong
- This is a very small, early-phase study with only 10 people, so results may not apply widely. The imaging technique is new and may not clearly show the expected changes.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
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Early phase 1
The earliest testing in people: a first look at safety, in a very small group.
- Participants
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About 10 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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Apr 2026
- Expected to finish
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Sep 2026
An estimate. End dates often move.
- Lead sponsor
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Other sponsor
The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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25 to 65 years
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: 1. Age between 25 and 65 years; 2. Current depression as assessed on the SCID; 3. Treatment-resistant depression, as defined by failure of at least two previous antidepressant or mood stabilizing treatments within the current depressive episode. Failed antidepressant or mood stabilizing treatments can include pharmacotherapy for depression at an adequate dose for at least 8 weeks 4. Able to comprehend English, as all questionnaires are in this language 5. Ability to provide informed consent Ability to pass a comprehension assessment test related to effects of ketamine and trial objectives and criteria. Exclusion Criteria: 1. A sleep disorder other than insomnia, as determined by history; 2. History of bipolar disorder, delirium, dementia, amnestic disorder, schizophrenia and other psychotic disorders as assessed on the SCID; 3. Alcohol or drug abuse in the past year based upon the SCID or urine toxicology screen; 4. A current smoker; 4\) Any significant medical or neurological illness that impacts brain function or impedes participation; 5) History of head trauma with significant loss of consciousness; 6) Metallic implants, pacemakers or tattoos, or other contraindications to MRI; Claustrophobic, or intolerant of the scanner environment; 7) For women, pregnancy will exclude participation. 8) Untreated hypertension Based on ketamine's known difficulties with induction of perceptual/psychomimetic symptoms, exclusion criteria for this study are as follows: 1. Patients with a BMI over 40. 2. Ongoing prescription of 4 mg lorazepam equivalents (total) daily, or morning dosing of any benzodiazepine at the time of assessment; 3. Currently undergoing ECT, transcranial magnetic stimulation, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression; 4. Use of any MAOI is prohibited two weeks prior to administration of study drug; if patients are on an MAOI when enrolled, study drug will not be administered until two weeks off MAOI; 5. CYP3A4 inducers carbamazepine and modafinil are prohibited two weeks prior to administration of study drug and at least 24 hours after last dose of study drug. 6. Current use of Naltrexone; 7. Developmental delay, mental retardation, or intellectual disorder; 8. Clinical or self-reported diagnosis of delirium, encephalopathy, or related clinical diagnosis within the prior 12 months; 9. Prior participation in another study of ketamine for depression 10. Prior treatment and/or recreational use of ketamine
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
How to take part
Only the study team decides who joins. These are the ways to reach them.
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The places running it
1 site. The list below names each one and where it is.
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The official record
ClinicalTrials.gov lists the study team's own contact details, including names and phone numbers. We don't republish those.
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A doctor treating you
A doctor who knows your case can contact a study site on your behalf, and can tell you whether this study is worth pursuing at all.
Contacts and locations
Locations
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University of Pennsylvania
RECRUITINGPhiladelphia, Pennsylvania, 19104, United States
More trials for these conditions
Other studies related to the condition(s) this trial covers.
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- A brain stimulation trial aims to rewire the circuit behind depression
- Can pairing ketamine with talk therapy beat depression alone?
- Genetic matchmaking for antidepressants: a global trial puts personalization to the test
- Could a common vitamin lift depression in young people?