Investigating how ketamine affects decision-making and emotions in depression

Glutamatergic Adaptation to Stress as a Mechanism for Anhedonia and Treatment Response With Ketamine

Early Phase 1 Interventional Emory University · NCT05327699

This study is testing how low doses of ketamine can affect decision-making and emotions in people with depression compared to healthy individuals.

Quick facts

PhaseEarly Phase 1
Study typeInterventional
Enrollment140 (estimated)
Ages18 Years to 65 Years
SexAll
SponsorEmory University Academic / other
Locations1 site (Atlanta, Georgia)
Trial IDNCT05327699 on ClinicalTrials.gov

What this trial studies

This study aims to explore the effects of sub-anesthetic doses of ketamine on individuals diagnosed with Major Depressive Disorder (MDD). It will assess changes in anhedonia, decision-making, and emotion processing through questionnaires, neuroimaging, and behavioral tasks. The trial will include MDD patients and a separate group of healthy controls for baseline comparisons. The primary goals are to evaluate the glutamate stress response in MDD patients and the impact of ketamine versus placebo on this response.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18-65 with a current diagnosis of Major Depressive Disorder and significant depressive symptoms.

Not a fit: Patients with a history of bipolar disorder, psychotic disorders, or recent substance abuse may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment strategies for patients with Major Depressive Disorder.

How similar studies have performed: Previous studies have shown promising results with ketamine in treating depression, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

MDD Patients:

* willing and able to give written informed consent
* men or women, 18-65 years of age
* primary diagnosis of DSM-V MDD, current, as diagnosed by the SCID-I
* score of ≥20 on the Beck Depression Inventory, which will include patients characterized as having "moderate/severe" (20-28) or "very-severe" (29-63) depressive symptoms
* off all antidepressant therapy for at least 8 weeks prior to the baseline visit

Healthy Controls:

* willing and able to give written informed consent
* men or women, 18-65 years of age

Exclusion Criteria:

MDD Patients:

* history of any bipolar disorder or psychotic disorder
* active psychotic symptoms of any type
* substance abuse/dependence within 6 months of study entry (as determined by SCID)
* unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination and laboratory testing), including upper respiratory disease or asthma, glaucoma or porphyria.
* active suicidal ideation as determined by a score ≥3 on the Columbia Suicide Severity Rating Scale (C-SSR)
* use of any recreational drugs as confirmed by urine drug screen at the time of scanning
* pregnancy or lactation
* use of glucocorticoids at any time during the study
* Raynaud's disease that may interfere with the cold-pressor
* contraindications for MRI
* MMSE score \<28
* elevated blood pressure prior to infusion (systolic \> 160 or diastolic \>100)
* history of treatment resistance as determined by ATRQ
* prior adverse reaction to ketamine
* use of antipsychotic medications
* use of greater than 2mg daily of lorazepam or similar benzodiazipine.
* Regular smoker as self-reported

Healthy Controls:

* evidence of any psychiatric disorder with exception of specific phobia, and no history of any psychiatric disorder except mild past substance use disorder as diagnosed by the SCID-I
* history of any substance abuse within the last 6 months
* use of any recreational drugs as confirmed by urine drug screen at the time of scanning
* pregnancy or lactation
* use of glucocorticoids at any time during the study
* Raynaud's disease that may interfere with the cold-pressor
* contraindications for MRI
* MMSE score \<28
* Regular smoker as self-reported

Where this trial is running

Atlanta, Georgia

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Major Depressive DisorderNeuroscienceStress response
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.