title: Separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ⁹-THC in humans discriminating Δ⁹-THC.
abstract: BACKGROUND
  Our previous research suggested the involvement of γ-aminobutyric acid (GABA), in particular the GABAB receptor subtype, in the interoceptive effects of Δ(9)-tetrahydrocannabinol (Δ(9)-THC). The aim of the present study was to determine the potential involvement of the GABAA receptor subtype by assessing the separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ(9)-THC using pharmacologically selective drug-discrimination procedures.
  
  
  METHODS
  Ten cannabis users learned to discriminate 30 mg oral Δ(9)-THC from placebo and then received diazepam (5 and 10mg), Δ(9)-THC (5, 15 and 30 mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected.
  
  
  RESULTS
  Δ(9)-THC functioned as a discriminative stimulus, produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug) and elevated heart rate. Diazepam alone impaired performance on psychomotor performance tasks and increased ratings on a limited number of self-report questionnaire items (e.g., Any Effect, Sedated), but did not substitute for the Δ(9)-THC discriminative stimulus or alter the Δ(9)-THC discrimination dose-response function. Similarly, diazepam had limited impact on the other behavioral effects of Δ(9)-THC.
  
  
  CONCLUSIONS
  These results suggest that the GABAA receptor subtype has minimal involvement in the interoceptive effects of Δ(9)-THC, and by extension cannabis, in humans.
authors.affiliation: Department of Behavioral Science, University of Kentucky College of Medicine, Medical Behavioral Science Building, Lexington, KY 40536-0086, USA; Department of Psychiatry, University of Kentucky College of Medicine, 3470 Blazer Pkwy, Lexington, KY 40509-1810, USA. Electronic address: jalile2@uky.edu.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Lile
authors.affiliation: Department of Behavioral Science, University of Kentucky College of Medicine, Medical Behavioral Science Building, Lexington, KY 40536-0086, USA; Department of Psychology, University of Kentucky College of Arts and Sciences, 106-B Kastle Hall, Lexington, KY 40506-0044, USA; Department of Psychiatry, University of Kentucky College of Medicine, 3470 Blazer Pkwy, Lexington, KY 40509-1810, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Kelly
authors.affiliation: Department of Psychiatry, University of Kentucky College of Medicine, 3470 Blazer Pkwy, Lexington, KY 40509-1810, USA; Department of Internal Medicine, University of Kentucky College of Medicine, 740 South Limestone St., J525 Kentucky Clinic, Lexington, KY 40536-0284, USA.
authors.forename: Lon R
authors.initials: LR
authors.lastname: Hays
mesh_terms: D000293:Adolescent; D000328:Adult; D000494:Allosteric Regulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D018757:GABA Modulators / Q000494:pharmacology*; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000523:psychology; D011597:Psychomotor Performance / Q000187:drug effects; D011963:Receptors, GABA-A / Q000378:metabolism*; D055815:Young Adult
chemical_list: D063386:Cannabinoid Receptor Agonists; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D013759:Dronabinol; D003975:Diazepam
keywords: Cardiovascular; Digit-symbol-substitution task; Drug discrimination; Marijuana; Repeated acquisition task; Subjective effects