• Joshua A Lile, Thomas H Kelly, and Lon R Hays.
• 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.
• Drug Alcohol Depend. 2014 Oct 1; 143: 141-8.

BackgroundOur 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.MethodsTen 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.ResultsΔ(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.ConclusionsThese results suggest that the GABAA receptor subtype has minimal involvement in the interoceptive effects of Δ(9)-THC, and by extension cannabis, in humans.Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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