DepressionNEMONCT06557642
Nitrous Oxide and EMOtional Cognition
A study testing Entonox and Medical Air in people with Depression, run by University of Oxford at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Depression
- What is being tested?
- Entonox and Medical Air
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 10 Jul 2024to 1 Oct 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 23Show fewer
- 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
- Diagnosed vitamin B12 deficiency
- Any use of recreational drugs in the last three months
- Participation in any other drug study in the last three months
- Participation in any other study with the same tasks in the last year
- OPTIONAL SLEEP STUDY ADD-ON Exclusion Criteria:
- Unable to undergo cardiac monitoring
- Unable to wear the sleep patch device for full monitoring period
- Implanted neurostimulator
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site, 1 recruiting
- Recruiting
Psychiatry Department
Oxford, OX3 7JX
Catherine Harmer, 01865 618200, catherine.harmer@psych.ox.ac.uk
About this study
Official title: Investigating the Neuropsychological Effects of Nitrous Oxide
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:
Read more
- 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
Read the detailed description
Questions regarding the mechanisms of nitrous oxide and its effects on the brain and behaviour in the context of its reported antidepressant effects remain largely unanswered. Thus, in the present study, the investigators aim to elucidate the more general effects that nitrous oxide might have on a series of neurocognitive processes which may be relevant to the treatment of depression. Namely, the study will investigate: 1) reconsolidation of autobiographical memories, 2) measures of emotional processing and emotional memory, 3) response inhibition, 4) cognitive flexibility and 5) sleep stages.
- Conditions
- Depression
- Being tested
- Entonox, Medical Air
- Keywords
- Healthy Volunteers
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EntonoxDrug
30 minute inhalation using demand valve and mouthpiece
Medical AirDrug
30 minute inhalation using demand valve and mouthpiece
| Study group | Role | What they receive |
|---|---|---|
| ENTONOX (50% nitrous oxide:50% oxygen) | Experimental | ENTONOX to be administered for 30 minutes. Receives: Drug: Entonox |
| Medical Air | Placebo comparator | Medical Air to be administered for 30 minutes. Receives: Drug: Medical Air |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 days before and 1 day after treatment
Secondary outcomes (3)
Performance on Emotional Processing Tasks
Performance on the Emotional Testing Battery (ETB), which contains an emotional word categorisation task, an emotional facial recognition task, and two emotional memory tasks.
Measured: Immediately before and after treatment and 1 day after treatment
Performance on Cognitive Flexibility Task
Performance on a probabilistic reversal learning task in which participants have to learn which strategy on a computer-task leads to a reward.
Measured: 1 day after treatment
Performance on Response Inhibition Task
Performance on an emotional go/no-go task in which participants have to inhibit their responses to certain stimuli based on rules given at the start of each block of the task.
Measured: 1 day after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2024
- Study start10 Jul 2024
- Primary completion15 Aug 2025 (estimated)
- Study completion1 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 88 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06557642
- Sponsor's protocol ID
- NEMO_Study
- Acronym
- NEMO
- Status last verified
- Jul 2025
- First submitted
- 19 Jul 2024
- Last updated
- 31 Jul 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Neuropsychological Effects of Nitrous Oxide
- ClinicalTrials.gov ID
- NCT06557642
- Acronym / sponsor ID
- NEMO / NEMO_Study
- Conditions
- Depression
- Keywords
- Healthy Volunteers
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 88 participants (estimated)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 10 Jul 2024 (actual)
- Primary completion
- 15 Aug 2025 (estimated)
- Study completion
- 1 Oct 2025 (estimated)
- First posted
- 16 Aug 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Questions regarding the mechanisms of nitrous oxide and its effects on the brain and behaviour in the context of its reported antidepressant effects remain largely unanswered. Thus, in the present study, the investigators aim to elucidate the more general effects that nitrous oxide might have on a series of neurocognitive processes which may be relevant to the treatment of depression. Namely, the study will investigate: 1) reconsolidation of autobiographical memories, 2) measures of emotional processing and emotional memory, 3) response inhibition, 4) cognitive flexibility and 5) sleep stages.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ENTONOX (50% nitrous oxide:50% oxygen) | Experimental | Drug: EntonoxENTONOX to be administered for 30 minutes. |
| Medical Air | Placebo comparator | Drug: Medical AirMedical Air to be administered for 30 minutes. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Entonox30 minute inhalation using demand valve and mouthpiece | Drug | ENTONOX (50% nitrous oxide:50% oxygen) |
| Medical Air30 minute inhalation using demand valve and mouthpiece | Drug | Medical Air |
Primary outcome
Changes in Emotional Ratings of Personal Memories (Memory Reconsolidation)
Time frame: 2 days before and 1 day after treatment
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.
3 secondary outcomes
Performance on Emotional Processing Tasks
Time frame: Immediately before and after treatment and 1 day after treatment
Performance on Cognitive Flexibility Task
Time frame: 1 day after treatment
Performance on Response Inhibition Task
Time frame: 1 day after treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Entonox and Medical Air in people with Depression, run by University of Oxford at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Emotional Ratings of Personal Memories (Memory Reconsolidation) (time frame: 2 days before and 1 day after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2025.