title: The Subjective Response to Nitrous Oxide is a Potential Pharmaco-Endophenotype for Alcohol Use Disorder: A Preliminary Study with Heavy Drinkers.
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.
authors.affiliation: Clinical Psychopharmacology Unit, Research Department of Clinical, Educational and Health Psychology, University College London, Gower Street, London.
authors.forename: Katie
authors.initials: K
authors.lastname: Walsh
authors.affiliation: Clinical Psychopharmacology Unit, Research Department of Clinical, Educational and Health Psychology, University College London, Gower Street, London.
authors.forename: Ravi K
authors.initials: RK
authors.lastname: Das
authors.affiliation: Clinical Psychopharmacology Unit, Research Department of Clinical, Educational and Health Psychology, University College London, Gower Street, London.
authors.forename: Sunjeev K
authors.initials: SK
authors.lastname: Kamboj
mesh_terms: D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000188:drug therapy* / Q000523:psychology*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000378:metabolism; D001007:Anxiety / Q000188:drug therapy / Q000209:etiology; D066249:Craving / Q000187:drug effects; D003863:Depression / Q000188:drug therapy / Q000209:etiology; D058068:Endophenotypes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009609:Nitrous Oxide / Q000008:administration & dosage* / Q000378:metabolism; D011569:Psychiatric Status Rating Scales; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D018712:Analgesics, Non-Narcotic; D009609:Nitrous Oxide
keywords: NMDA receptor; alcohol; alcohol use disorder; endophenotype; nitrous oxide