Nitrous Oxide Neuroimaging Study for Pain and Memory

This study aims to understand how low-dose nitrous oxide (laughing gas) affects your brain's response to pain and how you form memories. Researchers will use a nerve stimulator to create a mild, temporary pain sensation while you inhale nitrous oxide through a face mask. Brain scans (functional magnetic resonance imaging or fMRI) will be used to see how your brain activity changes with and without nitrous oxide during painful stimulation. The study is looking for 60 healthy volunteers between 18 and 59 years old who do not have certain medical conditions like chronic pain or sleep apnea. Success will be measured by observing differences in brain activation and connections when experiencing pain with and without nitrous oxide. The current recruitment status is unclear.

Study design
This is an interventional, non-randomized clinical trial involving 60 healthy volunteers. It compares brain activity during pain with and without nitrous oxide.
What's involved
You will participate in two visits. During these visits, you will inhale nitrous oxide and receive mild painful shocks while undergoing fMRI brain scans.
Compensation
Not stated in the trial record.
Follow-up
There is no long-term follow-up after the two study visits.

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NCT06702631

Nitrous Oxide Neuroimaging

Completed
EARLY_PHASE1Ages 18–59InterventionalBasic science
Keith M Vogt
~34 participants
Updated 2026-08-19 on ClinicalTrials.gov
What's tested:Nitrous oxidePeripheral Nerve Stimulation

At a glance

Recruiting sites
0 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Brain activation to painful stimulation difference: Drug-free condition minus nitrous oxide condition
Measured over Visit 1: Immediate; average activity, calculated from each task scan
+1 more outcome measured
Anesthesia
Pain
Amnesia
1 sites across 1 states
Pennsylvania1

This trial hasn't published a contact. View it on ClinicalTrials.gov

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Eligibility criteria

Exclusion

have a valid email address and valid phone number throughout the study
free from any non-MRI compatible implants
are pregnant or attempting to conceive
body mass index (BMI) \> 35
significant memory impairment or hearing loss
sleep apnea
chronic pain or frequently taking pain medication (including tramadol)
any severe or poorly-controlled medical problem (hypertension, diabetes)
neurologic or psychiatric disease, including anxiety, and depression
severe cardiac disease
history of methylenetetrahydrofolate reductase (MTHFR) deficiency or variant mutation, as assessed by personal report
recent ear or eye surgery
being claustrophobic
have metal implants or non-removable metal piercings
having a history of adverse reaction to anesthetics
daily alcohol or heavy alcohol use; history of alcohol abuse
current daily smoker
regular or recent marijuana use (including prescribed/medical marijuana)
illicit drug use, i.e., street drugs
regularly taking: antiepileptics, antidepressants, anti-psychotics, antihistamines, anti-anxiety medication, stimulants, or sleep-aids
  • Brain activation to painful stimulation difference: Drug-free condition minus nitrous oxide conditionVisit 1: Immediate; average activity, calculated from each task scan

    Event-related blood-oxygen level dependent Magnetic Resonance Imaging (MRI) responses will be determined. Z-scores will be calculated by linear regression of the task timing against the MRI signal time-course (MRI data is in arbitrary units with no maximum or minimum) at each voxel (single data point in brain). Primary outcome will be for the right insula. Z-score of 0 indicates no task-related changes. Z-scores further from zero indicate stronger correlation between functional MRI signal change and the task timing, with positive values indicating increases in functional MRI signal and negative Z-scores indicating decreases. Practically, higher positive Z-scores would indicate increased brain activity and larger negative Z-scores would indicate decreased brain activity.

  • Resting-state functional connectivity difference: Drug-free minus nitrous oxide conditionVisit 1: Immediate; brain activity captured in data acquired across entire 6-8 minute scan.

    Functional connectivity (FC) will be calculated as the correlation between the time-series of MRI signal (MRI data is in arbitrary units with no maximum or minimum) on a pair-wise basis between every atlas-defined region in the brain. Strength of temporal correlation is reflective of brain regions that are working together, and changes in FC reflect differences in brain state, in this case between the drug-free and nitrous oxide conditions. The reported value will be for FC change between insula and anterior cingulate. T-score of 0 would indicate no condition-related changes in connectivity between the two brain regions. T-scores further from zero indicate stronger connectivity change: positive T-score reflects drug-free \> nitrous oxide; negative T-scores indicate nitrous oxide \> drug-free.