Developing Anesthesia as Post Traumatic Stress Disorder (PTSD) Therapy

Study Overview
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Brief Summary
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This preclinical phase 1 development study in healthy volunteers seeks to identify if low doses of commonly used non-triggering anesthetic agents might have clinical utility for modulating emotional memory processing and to understand the nature of the brain mechanisms of drug action. Optimally, a drug, dose and brain mechanism of action will be identified that will form the foundation for future use in clinical studies of patients with PTSD.

Official Title
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Developing Anesthesia as PTSD Therapy

Conditions
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Healthy

Intervention / Treatment
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* Drug: Dexmedetomidine
* Drug: Propofol
* Drug: Ketamine
* Drug: Nitrous Oxide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults. Between the ages of 18 and 35. Exclusion Criteria: Pregnancy. Left-handed. Unusual facial anatomy. History of esophageal reflux. Respiratory problems. Central nervous system disorders. Cardiovascular problems. Kidney disease. Diabetes. History of Substance abuse. History of adverse anesthetic reactions. Hepatitis. Failure to pass MRI screening questionnaire. Fear of small-enclosed spaces. Mental illness. Non-native English speakers.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo | Drug: Dexmedetomidine<br>* A low dose of dexmedetomidine is used during scanning after dose piloting outside the scanner for memory effects and tolerability.<br>Drug: Propofol<br>* A low dose of propofol is used during scanning after dose piloting outside the scanner for memory effects and tolerability.<br>Drug: Ketamine<br>* A low dose of ketamine is used during scanning after dose piloting outside the scanner for memory effects and tolerability.<br>Drug: Nitrous Oxide<br>* A low dose of nitrous oxide is used during scanning after dose piloting outside the scanner for memory effects and tolerability.<br>Drug: Placebo<br>* Placebo<br>|
| Experimental: Dexmedetomidine<br>Dexmedetomidine intravenous infusion during scan. | Drug: Dexmedetomidine<br>* A low dose of dexmedetomidine is used during scanning after dose piloting outside the scanner for memory effects and tolerability.<br>|
| Experimental: Propofol<br>Propofol intravenous infusion during scan. | Drug: Propofol<br>* A low dose of propofol is used during scanning after dose piloting outside the scanner for memory effects and tolerability.<br>|
| Experimental: Ketamine<br>Ketamine intravenous infusion during scan. | Drug: Ketamine<br>* A low dose of ketamine is used during scanning after dose piloting outside the scanner for memory effects and tolerability.<br>|
| Experimental: Nitrous Oxide<br>Nitrous Oxide inhalation during scan. | Drug: Nitrous Oxide<br>* A low dose of nitrous oxide is used during scanning after dose piloting outside the scanner for memory effects and tolerability.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of events remembered | The proportion of items remembered in long-term memory 4 days after viewing emotional or neutral pictures. | Day 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-related fMRI BOLD signals | Evoked fMRI responses to emotional and neutral pictures are measured and later correlated with subsequent memory performance. | Baseline |