title: The effect of a clinically effective and non-effective dose of lorazepam on 7.5% CO₂-induced anxiety.
abstract: Symptoms of anxiety induced by 7.5% CO₂ inhalation can be attenuated by acute administration of GABA(A) receptor anxiolytics such as lorazepam and alprazolam. This study investigated if these effects are dose-related, by comparing a 0.5 mg dose (considered non-clinically effective) and a 2 mg dose of lorazepam (clinically effective) on 7.5% CO₂ inhalation. Eighteen healthy males (mean age 20.6 years, SD 1.29), judged physically and mentally fit, attended three visits, each one week apart, to take each treatment in a randomised double-blind crossover design. Drugs were given 60 min prior to 20 min air inhalation, followed by 20 min 7.5% CO₂ inhalation. The order of gas presentation was single blind. Subjective ratings using visual analogue scales (VAS) and questionnaires were recorded before and after each inhalation. Blood pressure (BP), heart rate (HR), respiration rate (RR) and expired CO₂ were recorded during each inhalation. Inhalation of 7.5% CO₂ significantly raised BP, HR, RR and expired CO₂. Ratings of feeling like leaving the room were significantly lower on 2 mg compared with 0.5 mg and placebo, and dose-dependent trends were seen in scores for VAS fearful, anxious, stressed, tense, and worried. Results may be indicative of dose-dependent effects of lorazepam in a CO₂ model of anxiety.
authors.affiliation: Psychopharmacology Unit, University of Bristol, Academic Unit of Psychiatry, Bristol, UK. alison_diaper@hotmail.com
authors.forename: Alison
authors.initials: A
authors.lastname: Diaper
authors.forename: Andreas
authors.initials: A
authors.lastname: Papadopoulos
authors.forename: Ann S
authors.initials: AS
authors.lastname: Rich
authors.forename: Gerry R
authors.initials: GR
authors.lastname: Dawson
authors.forename: Colin T
authors.initials: CT
authors.lastname: Dourish
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.forename: Jayne E
authors.initials: JE
authors.lastname: Bailey
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001007:Anxiety / Q000517:prevention & control*; D001237:Asphyxia / Q000209:etiology / Q000523:psychology*; D002245:Carbon Dioxide / Q000008:administration & dosage / Q000009:adverse effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D058785:GABA-A Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008140:Lorazepam / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D011569:Psychiatric Status Rating Scales; D015203:Reproducibility of Results; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D014151:Anti-Anxiety Agents; D058785:GABA-A Receptor Agonists; D002245:Carbon Dioxide; D008140:Lorazepam