The effects of nitrous oxide (‘laughing gas’) on thoughts and feelings in healthy people
| ISRCTN | ISRCTN16259778 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16259778 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Protocol serial number | V1 |
| Sponsor | University College London |
| Funder | Find a Better Way |
- Submission date
- 27/08/2019
- Registration date
- 28/08/2019
- Last edited
- 13/08/2021
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Other
Plain English summary of protocol
Background and study aims
Nitrous oxide (‘laughing gas’) has a variety of effects on mood and thinking. In this study we are looking at whether nitrous oxide produces some of the same effects as ketamine and alcohol. Both of these drugs interact with a brain neurotransmitter receptor called the NMDA receptor, blocking its usual functioning. Nitrous oxide is also thought to have its effects via this receptor, and as such we expect that it will produce similar effects to both alcohol and ketamine.
For example, ketamine produces disturbances in thinking that resemble psychosis, and nitrous oxide may produce some similar (temporary) disturbances in experience. Ketamine also produces effects that resemble alcohol intoxication, so nitrous oxide is expected to share this property with ketamine as well.
Some of these effects might depend on certain personality characteristics or family background, so we are testing this possibility in the current study by asking participants to complete questionnaires about their traits and general moods.
Who can participate?
Women and men aged between 18 and 40, who are healthy and have no psychiatric or physical health conditions that could make nitrous oxide inhalation unsafe.
What does the study involve?
The study involves attending a single session at University College London.
Before arriving at this session, participants will need to complete a screening questionnaire and interview to ensure they are suitable. We will ask about their physical and mental health and their typical (alcohol) drinking habits.
Participants will be randomly assigned to receive either medical air, which is the same as the air we usually breathe, or Entonox, which is the commercial name for nitrous oxide, and contains 50 % nitrous oxide mixed with 50% oxygen. Before inhaling either gas, participants will complete a series of questionnaires about their typical thoughts and feelings, as well as their current thoughts and feelings. They will also be asked questions about whether any of their family members have a history of problems with alcohol use. They will then start inhaling the gas and repeat some of these questionnaires. After completing all of the questionnaires, participants stop inhaling the gas and sit quietly for 15 minutes. They then repeat a final set of questionnaires. They will be able to leave the lab when at least 30 min has elapsed since they stopped gas inhalation.
What are the possible benefits and risks of participating?
Participants are reimbursed, but there are no personal health benefits associated with taking part. However, by taking part, participants will be helping us understand how nitrous oxide and similar drugs work, and how these might eventually be used to treat people with psychological disorders. As such, participants usually find this kind of study interesting and rewarding.
The research is considered to be low risk. However, as with any study involving the use of medications, it is not possible to eliminate all risks. There are no known long-term risks associated with the study, however, in the short-term, participants who receive nitrous oxide gas might experience some acute side effects such as dry mouth, numbness, nausea and vomiting and dizziness. Because nitrous oxide leaves the body quickly after inhalation stops, these effects reverse quickly. Participants will remain in the department for at least 30 min after the inhalation stops to ensure all effects have worn off.
Where is the study run from?
The study is run from the research department of the Clinical Psychopharmacology Unit, University College London, which is located at 1-19 Torrington Place, London.
When is the study starting and how long is it expected to run for?
The approximate start date for the study is 4th Sept 2019. We expect the study to run for about 5 months.
Who is funding the study?
The study is funded by the UK registered charity Find a Better Way.
Who is the main contact?
Professor Sunjeev Kamboj, sunjeev.kamboj@ucl.ac.uk
Contact information
Scientific
Research Dept Clinical, Educational and Health Psychology
UCL
London
WC1E 6BT
United Kingdom
 ORCID ID |
0000-0003-2197-0826 |
|---|---|
| Phone | 0207 679 2000 |
| sunjeev.kamboj@ucl.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomised (non-clinical), single blind, placebo-controlled experiment |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | The effects of nitrous oxide on psychosis-like and psychedelic experiences in healthy volunteers: a single-blind randomized experimental study |
| Study acronym | N/A |
| Study objectives | 1. We hypothesise that due to its NMDA receptor antagonist properties, inhalation of 50% nitrous oxide (N2O; ‘Entonox’) will produce a temporary psychosis-like state in healthy individuals, reflected in elevated scores on the Psychotomimetic States Inventory (PSI; Mason et al, 2008) during N2O inhalation relative to baseline, with no appreciable ‘pre-to-during inhalation’ change in the medical air group. In addition, we predict a pattern of responding on an adapted version of the Questionnaire of Altered States of Consciousness during inhalation of N2O (but not medical air) that resembles the pattern seen during ketamine infusions (Studerus et al, 2010). These psychedelic effects will only be measured once (during gas inhalation) and compared descriptively to previously published findings (Studerus et al, 2010). Both psychosis-like and psychedelic effects are expected to reverse rapidly (return to baseline) upon termination of inhalation of N2O (by the 15 min post-inhalation time-point). 2. We hypothesise that subjective effects of N2O will resemble those produced by alcohol. We predict that participants will rate their experiences of N2O as similar to alcohol (Krystal et al, 1998). Those with experience of alcohol as well as cannabis (a psychotomimetic) and/or cocaine (a stimulant) will rate the similarity between the effects of N2O and alcohol higher than the similarity between the effects of N2O and cannabis or cocaine. Only participants in the N2O group will also show increased sedative and stimulant effects on the Biphasic Alcohol Effects Scale (BAES-brief) during inhalation relative to pre-inhalation. 3. We hypothesise that bipolar phenotype will moderate the subjective response to N2O in a similar manner to the phenotypic moderation of the response to alcohol (Yip et al, 2012). Specifically, we predict that participants expressing a bipolar phenotype (high scores on the Mood Disorders Questionnaire; Hirschfeld et al, 2000) will show lower sensitivity to the subjective effects of N2O during inhalation than participants with the ‘no-bipolar’ phenotype. |
| Ethics approval(s) | Approved 30/01/2019, University College London Research Ethics Committee (Research Ethics Office, Office of the Vice-Provost (Research), University College London, 2 Taviton St, London WC1E 6BT; 020 7679 8717 extension 28717; ethics@ucl.ac.uk), ref: 3901/001. |
| Health condition(s) or problem(s) studied | Psychosis-like, psychedelic and alcohol-like states induced by nitrous oxide in healthy volunteers |
| Intervention | Medical air (placebo, BOC, UK) or Entonox (BOC, UK), which is a premixed gas containing 50% N20 and 50% oxygen. For hypothesis 1 (psychosis-like and psychedelic effects) and hypothesis 2 (alcohol-like effects), the primary between-subjects factor is Group, with two levels (N2O; medical air). The within-subjects factor (Time) has three levels (pre-inhalation, on-gas, post-inhalation). Fifty participants will be equally and randomly assigned to Group using a random number generation procedure (using a combination of RAND(), RANK(), RANK/n and CEILING.MATH functions in Excel). These ‘non-purposively’ recruited participants will be assigned to Group (medical air placebo: n=25; N2O: n=25) without reference to scores on trait measures and will form the sample used to address hypothesis 1 (psychosis-like and psychedelic effects) and hypothesis 2 (alcohol-like effects). An additional n=30 participants will be purposively recruited to examine hypothesis 3, based on high ‘trait’ scores (>= 7) on the Mood Disorders Questionnaire (MDQ). These n=30 high-scoring participants will contribute to one level (‘bipolar’) of an additional between-subjects factor: ‘Phenotype’, and will also be equally and randomly assigned to N2O and medical air using the same randomization procedure as above (medical air: n=15; N2O: n=15). ‘Non-bipolar’ participants (the other level of the Phenotype factor) will be the n=30 (medical air: n=15; N2O: n=15) lowest scoring participants from the initial n=50, non-purposively recruited sample. |
| Intervention type | Drug |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Medical air (placebo, BOC, UK) Entonox (BOC, UK; premixed as 50% N20 : 50% oxygen) |
| Primary outcome measure(s) |
Psychosis-like/Psychedelic effects of N2O |
| Key secondary outcome measure(s) |
Additional measures below are potentially important covariates/moderators (especially the MDQ scores) or cofounding factors (rather than ‘outcomes’ per se) that we wish to assess for similarity between groups at baseline or test in exploratory analyses: |
| Completion date | 06/12/2019 |
Eligibility
| Participant type(s) | Healthy volunteer |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 40 Years |
| Sex | All |
| Target sample size at registration | 80 |
| Total final enrolment | 80 |
| Key inclusion criteria | 1. Age: 18-40 2. Fluency in written and spoken English 3. Consumes alcohol as social drinker 4. For hypothesis related to moderation of subjective effects by bipolar phenotype, participants will be high scores (>=7) on the Mood Disorder Questionnaire |
| Key exclusion criteria | 1. Are pregnant or are likely to become pregnant during the study or breastfeeding. 2. Suffer from any major physical health disorder 3. Are currently seeking/receiving treatment for any psychiatric condition 4. Have asthma or any breathing difficulty (including sleep apnoea) 5. Have a cardiovascular condition or a fitted pacemaker 6. Have any liver or kidney disorder 7. Have had a ‘collapsed lung’ 8. Have difficulties metabolising vitamin B12 9. Have anaemia 10. Have history of stomach ulcers 11. Have high or low blood pressure 12. Have a current ear or sinus infection or a bad cold 13. Have epilepsy 14. Have ever had neurosurgery 15. Are diabetic 16. Have had any recent dental work or dental infection/inflammation 17. Have had any adverse reaction to nitrous oxide in the past 18. Use recreational drugs more than once a week 19. Are unable/unwilling to abstain from drugs and alcohol for 24 hours prior to the study |
| Date of first enrolment | 04/09/2019 |
| Date of final enrolment | 02/12/2019 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centre
Research Dept Clinical, Educational and Health Psychology
Univerity College London
Gower Street
London
WC1E 6BT
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | Yes |
|---|---|
| IPD sharing plan summary | Available on request |
| IPD sharing plan | The datasets generated during the current study will be available upon reasonable request from Professor Sunjeev Kamboj (sunjeev.kamboj@ucl.ac.uk), Principal Investigator. The data will be available from approximately Jan 2021. Data will include relevant group allocations and outcome variables and will be anonymised. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 23/07/2021 | 13/08/2021 | Yes | No | |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
Editorial Notes
13/08/2021: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
01/12/2020: The intention to publish date was changed from 01/09/2020 to 01/03/2021.
18/12/2019: The following changes have been made:
1. The recruitment end date has been changed from 04/01/2020 to 02/12/2019.
2. The overall trial end date has been changed from 01/02/2020 to 06/12/2019.
28/08/2019: Trial's existence confirmed by the University College London Research Ethics Committee.
