Understanding the Role of the Kappa Opioid Receptor in Ketamine's Attenuation of Suicidal Thoughts

March 23, 2026 updated by: Elizabeth Bartlett, New York State Psychiatric Institute

Dynorphin/Kappa Opioid Receptor Signaling Role in Ketamine's Anti-suicidal Ideation Effect

This study explores how stress, suicidal thoughts, and ketamine's effects are connected in people with major depressive disorder. Stress increases the risk for suicidal thoughts, but the biological basis is unclear. Ketamine may help reduce suicidal thoughts by affecting stress-linked brain systems. This study will use smartphone tracking to monitor real-time responses to stress and positron emission tomography (PET) brain scans to study how ketamine affects brain pathways related to stress and suicidal thoughts in depressed individuals.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

12

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10032
        • New York State Psychiatric Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • DSM5 unipolar major depressive episode
  • Persons of child-bearing potential must agree to use an acceptable method of birth control throughout the study.

Exclusion Criteria:

  • Current or past ketamine abuse or dependence ever (lifetime)
  • Any medical contraindication to ketamine, including prior ineffective trial of or medically significant adverse reaction to ketamine.
  • Clinically significant EKG abnormality in terms of ketamine administration (e.g., Ventricular tachycardia, evidence of myocardial ischemia, symptomatic bradycardia, unstable tachycardia, second degree (or greater) AV block).
  • Lifetime schizophrenia, schizoaffective illness, bipolar disorder, current psychotic depression; mild drug or alcohol use disorder in past 2 months; moderate or severe drug or alcohol use disorder in past 6 months; suicidal ideation with plan and/or intent within 6 months; suicide attempt in the past month.
  • A first-degree family history of schizophrenia if the subject is less than 33 years old (mean age of onset for schizophrenia plus two standard deviations).
  • Current or recent use of antidepressants within 14 days or benzodiazepines within 1 day. Use of fluoxetine or other long-acting antidepressant within 6 weeks.
  • Current or recent use of medications known to affect brain biology of interest such as competing for binding sites of PET tracer within 1 month.
  • Uncontrolled moderate or severe hypertension (≥160 mmHg systolic or ≥100 mmHg diastolic[41]), history of Raynaud's phenomenon, seizures, an open cut, sore, or bone fracture on or near the hands to be used for the cold pressor test.
  • Use of more than incidental NSAIDs (including aspirin), anti-inflammatories, immune suppressants or other pain medications.
  • Significant active physical illness, particularly if it may affect the brain biology being studied; including chronic pain syndrome and medically compromising eating disorders or epilepsy.
  • Lacks capacity to consent
  • Aggressive behavior that is a significant threat to others such as physically assaultive behavior (in the last month).
  • Pregnancy, abortion or miscarriage in the previous two months or plans to conceive during the course of study participation.
  • Currently lactating
  • Previous head injury with evidence of cognitive impairment. Subjects who endorse a history of prior head trauma and score 1.5 standard deviations below the mean on Trail-making A or B will be excluded from study participation.
  • Any condition or material in the body that is a contraindication for MRI procedures.
  • Current, past or anticipated exposure to radiation except if the exposure was at our PET center where the precise exposure is known
  • ECT within past 6 months
  • For A-Line Subjects: Unstable relevant medical condition (i.e., condition not adequately stabilized for 3 months). Including bleeding disorders, the need to take medications that affect blood clotting, and certain platelet and hemoglobin cutoffs
  • Blind or with visual impairment that cannot be corrected with corrective lenses (glasses or contact lenses)
  • No emergency contact

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ketamine
single racemic ketamine hydrochloride 0.5 mg/kg infusion
Drug: Ketamine hydrochloride infusion
single racemic ketamine hydrochloride 0.5 mg/kg infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Scale for Suicidal Ideation (SSI)
Time Frame: 24 hours post-treatment
Beck Scale for Suicidal Ideation clinician-rated version. Minimum score = 0, Maximum score = 38. Higher scores mean a worse outcome.
24 hours post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New York State Psychiatric Institute

Collaborators

American Foundation for Suicide Prevention

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

May 1, 2028

Study Completion (Estimated)

May 1, 2028

Study Registration Dates

First Submitted

August 18, 2025

First Submitted That Met QC Criteria

August 18, 2025

First Posted (Actual)

August 24, 2025

Study Record Updates

Last Update Posted (Actual)

March 24, 2026

Last Update Submitted That Met QC Criteria

March 23, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00089428
  • ECR-0-013-24 (Other Grant/Funding Number: American Foundation for Suicide Prevention)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All associated research findings published will be made readily available for research purposes to qualified individuals within the scientific community. All data will be made anonymous (de-identified) and available after written requests for data are submitted by such qualified individuals to the PI.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Major Depressive Disorder (MDD)

Clinical Trials on Ketamine hydrochloride infusion

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Luxembourg

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe