Nitrous Oxide and EMOtional Cognition

NCT06557642 | Recruiting

• 1 other identifier: NEMO_Study
• Study Type: interventional
• Target: 88
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to uncover the underlying neuropsychological mechanisms of nitrous oxide, which may be relevant to its reported antidepressant effects. In particular, the study is designed to determine whether nitrous oxide changes the way in which healthy volunteers aged 18-40 years remember negative autobiographical memories. The main question the study aims to answer is:

• Does nitrous oxide interfere with the emotional aspects of negative autobiographical memories? Other neuropsychological effects will also be assessed (e.g., emotional processing, emotional memory, response inhibition, and cognitive flexibility). Researchers will compare ENTONOX (50% nitrous oxide: 50% oxygen) with medical air. Participants will:
• Attend three research visits (screening, inhalation, follow-up)
• Take part in a 30 minute inhalation session of ENTONOX or medical air
• Complete a series of cognitive tasks
• Finish a series of self-report questionnaires

Conditions

Depression

Keywords

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Changes in Emotional Ratings of Personal Memories (Memory Reconsolidation)

  Negative/positive valence ratings associated with personal memories. A series of positive and negative adjectives will be presented to participants and they will have to rate on a scale of 1(not at all) to 10 (extremely) to what extent these words apply to how they feel when recalling the memory.

  2 days before and 1 day after treatment

Secondary Outcomes (3)

• Performance on Emotional Processing Tasks

  Immediately before and after treatment and 1 day after treatment

• Performance on Cognitive Flexibility Task

  1 day after treatment

• Performance on Response Inhibition Task

  1 day after treatment

Study Arms (2)

ENTONOX (50% nitrous oxide:50% oxygen)

EXPERIMENTAL

ENTONOX to be administered for 30 minutes.

Drug: Entonox

Medical Air

PLACEBO COMPARATOR

Medical Air to be administered for 30 minutes.

Drug: Medical Air

Interventions

Entonox DRUG

30 minute inhalation using demand valve and mouthpiece

ENTONOX (50% nitrous oxide:50% oxygen)

Medical Air DRUG

30 minute inhalation using demand valve and mouthpiece

Medical Air

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18-40 years
• Good vision and hearing
• Willing and able to give informed consent
• Body mass index (BMI) within the range of 18-35kg/m2 (This is to ensure we exclude underweight individuals who might have more substantial reactions to the nitrous oxide).
• Sufficiently fluent in English to understand tasks
• Willing to avoid drinking any alcohol from 3 days prior to Visit One until the end of Visit Three
• Willing to avoid using recreational drugs for 3 months prior to Visit One and throughout the duration of the study

You may not qualify if:

• Receiving or seeking treatment for any mental health condition (covered in Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-5 (SCID) assessment in screening procedures)
• History of any mental health condition (covered in SCID assessment in screening procedures)
• Attention deficit hyperactivity disorder (ADHD) requiring treatment with stimulant or other centrally-acting drugs
• A positive drug test for any of the following: amphetamine, barbiturates, benzodiazepines, buprenorphine, cocaine, marijuana, methadone, methamphetamine, methylenedioxymethamphetamine (MDMA), morphine, methaqualone, opiates, phencyclidine, propoxyphene, tricyclic antidepressants, tramadol, ketamine, oxycodone, cotinine, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), fentanyl, synthetic marijuana, 6-mono-acetyl-morphine (6-MAM).
• Regularly drink 14 or more units of alcohol a week
• Any eye, throat or ear surgery or a medical procedure requiring intravenous injection or line into a vein in the last 6 months
• A head injury causing concussion or unconsciousness in the past 6 months
• A collapsed lung or lung surgery (e.g., pneumothorax)
• A history of cardiac arrhythmias
• Current injuries of the face or mouth (including ulcers or dental problems)
• Dental surgery in the past month
• Deep diving or scuba diving (which has a risk of decompression sickness) in past month
• Pregnancy / intention to become pregnant during the study
• Breastfeeding during the study
• Asthma, emphysema or any medical condition that affects the lungs or breathing

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Psychiatry Department

Oxford, OX3 7JX, United Kingdom

RECRUITING

MeSH Terms

Conditions

Depression

Interventions

Entonox; Air

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Atmosphere; Environment; Ecological and Environmental Phenomena; Biological Phenomena; Meteorological Concepts; Environment and Public Health

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 19, 2024
• First Posted: August 16, 2024
• Study Start: July 10, 2024
• Primary Completion: August 15, 2025
• Study Completion: October 1, 2025
• Last Updated: July 31, 2025

Record last verified: 2025-07

Locations

GB (1)