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Separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ⁹-THC in humans discriminating Δ⁹-THC.
Drug Alcohol Depend. 2014 Oct 01; 143:141-8.DA

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+Show Affiliations

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.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.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.

Pub Type(s)

Controlled Clinical Trial
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25124305

Citation

Lile, Joshua A., et al. "Separate and Combined Effects of the GABAA Positive Allosteric Modulator Diazepam and Δ⁹-THC in Humans Discriminating Δ⁹-THC." Drug and Alcohol Dependence, vol. 143, 2014, pp. 141-8.
Lile JA, Kelly TH, Hays LR. Separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ⁹-THC in humans discriminating Δ⁹-THC. Drug Alcohol Depend. 2014;143:141-8.
Lile, J. A., Kelly, T. H., & Hays, L. R. (2014). Separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ⁹-THC in humans discriminating Δ⁹-THC. Drug and Alcohol Dependence, 143, 141-8. https://doi.org/10.1016/j.drugalcdep.2014.07.016
Lile JA, Kelly TH, Hays LR. Separate and Combined Effects of the GABAA Positive Allosteric Modulator Diazepam and Δ⁹-THC in Humans Discriminating Δ⁹-THC. Drug Alcohol Depend. 2014 Oct 1;143:141-8. PubMed PMID: 25124305.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ⁹-THC in humans discriminating Δ⁹-THC. AU - Lile,Joshua A, AU - Kelly,Thomas H, AU - Hays,Lon R, Y1 - 2014/07/29/ PY - 2014/05/22/received PY - 2014/07/10/revised PY - 2014/07/14/accepted PY - 2014/8/16/entrez PY - 2014/8/16/pubmed PY - 2015/9/17/medline KW - Cardiovascular KW - Digit-symbol-substitution task KW - Drug discrimination KW - Marijuana KW - Repeated acquisition task KW - Subjective effects SP - 141 EP - 8 JF - Drug and alcohol dependence JO - Drug Alcohol Depend VL - 143 N2 - 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. SN - 1879-0046 UR - https://www.unboundmedicine.com/medline/citation/25124305/Separate_and_combined_effects_of_the_GABAA_positive_allosteric_modulator_diazepam_and_Δ⁹_THC_in_humans_discriminating_Δ⁹_THC_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0376-8716(14)00988-0 DB - PRIME DP - Unbound Medicine ER -