The Subjective Response to Nitrous Oxide is a Potential Pharmaco-Endophenotype for Alcohol Use Disorder: A Preliminary Study with Heavy Drinkers.
Katie Walsh, Ravi Das, Sunjeev K. Kamboj
The International Journal of Neuropsychopharmacology April 1, 2017 DOI: 10.1093/ijnp/pyw063 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 60 |
| Population | Heavy drinkers who were otherwise healthy |
| Dose | 50% |
| Topics | Addiction |
| Keywords | Nmda receptor Endophenotype Nitrous oxide |
| Key findings | Participants with a family history of alcohol-use disorders showed an enhanced stimulation-to-sedation ratio during N2O inhalation compared to those without such familial risk. |
Abstract
Healthy people with a family history of alcohol problems show a pattern of subjective responses to alcohol that resemble those of affected probands. Studies on ketamine suggest that up-regulation of N-methyl-D-aspartate receptors (NMDARs) underlies these effects, and point to a pharmacologically-responsive endophenotype reflecting enhanced risk for alcohol-use disorders. Subjective stimulant and sedative effects were assessed before and during nitrous oxide (N2O; 50%) inhalation in heavy drinkers who were otherwise healthy. Participants with an ostensible family history of alcohol-use disorders (n = 23) were distinguishable from those without such familial risk (n = 37) by an enhanced stimulation-to-sedation ratio during N2O inhalation. The pattern of subjective effects of N2O according to familial risk is remarkably similar to that previously seen with ketamine, supporting the idea of a common, NMDAR-mediated mechanism of action. N2O may prove to be a safe and accessible alternative to ketamine for probing heritable NMDAR dysregulation in neuropsychiatric disorders.
Comparable studies
Other observational and cohort studies on addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population | 2013 | Observational study | |
| Dynamic coupling of whole-brain neuronal and neurotransmitter systems Healthy humans | 2020 | Observational study | |
| Psychedelics not linked to mental health problems or suicidal behavior: A population study Randomly selected United States adults | 2015 | Observational cohort | n = 135,095 |
| Breakdown of long-range temporal dependence in default mode and attention networks during deep sleep Human participants across the nonrapid eye movement sleep cycle | 2013 | Observational cohort | |
| Assessment of addiction severity among ritual users of ayahuasca Regular ayahuasca users (jungle-based and urban-based) and matched controls | 2010 | Observational cohort | n = 127 |
Citations in the library
Cited by 8
- Ultra-Brief Mindfulness Training Reduces Alcohol Consumption in At-Risk Drinkers: A Randomized Double-Blind Active-Controlled Experiment The International Journal of Neuropsychopharmacology July 28, 2017
- Examining memory reconsolidation as a mechanism of nitrous oxide's antidepressant action. Neuropsychopharmacology March 1, 2025
- Novel and emerging anesthetic drugs for the treatments of major depression: a comprehensive review of efficacy, mechanism, and outlook. Frontiers in Psychiatry 2025
- Nitrous Oxide Abuse: Clinical Outcomes, Pharmacology, Pharmacokinetics, Toxicity and Impact on Metabolism. Toxics November 28, 2023
- What is better for psychiatry: Titrated or fixed concentrations of nitrous oxide? Frontiers in Psychiatry 2022
and 3 more in the library
Cites 6
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- The use of ketamine as an antidepressant: a systematic review and meta‐analysis Human Psychopharmacology: Clinical and Experimental April 7, 2015
- Altered NMDA Glutamate Receptor Antagonist Response in Individuals With a Family Vulnerability to Alcoholism American Journal of Psychiatry October 1, 2004
- Nitrous oxide speeds the reduction of distressing intrusive memories in an experimental model of psychological trauma Psychological Medicine March 3, 2016
- Nitrous Oxide for Treatment-Resistant Major Depression: A Proof-of-Concept Trial. Biological Psychiatry July 1, 2015
and 1 more in the library