Separate and combined effects of the GABAA positive allosteric modulator diazepam and δ9-THC in humans discriminating δ9-THC

Joshua A. Lile; Thomas H. Kelly; Lon R. Hays

doi:10.1016/j.drugalcdep.2014.07.016

Separate and combined effects of the GABA_A positive allosteric modulator diazepam and δ⁹-THC in humans discriminating δ⁹-THC

Joshua A. Lile, Thomas H. Kelly, Lon R. Hays

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Background: Our previous research suggested the involvement of γ-aminobutyric acid (GABA), in particular the GABA_B receptor subtype, in the interoceptive effects of δ⁹-tetrahydrocannabinol (δ⁹-THC). The aim of the present study was to determine the potential involvement of the GABA_A receptor subtype by assessing the separate and combined effects of the GABA_A positive allosteric modulator diazepam and δ⁹-THC using pharmacologically selective drug-discrimination procedures. Methods: Ten cannabis users learned to discriminate 30mg oral δ⁹-THC from placebo and then received diazepam (5 and 10mg), δ⁹-THC (5, 15 and 30mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected. Results: δ⁹-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 δ⁹-THC discriminative stimulus or alter the δ⁹-THC discrimination dose-response function. Similarly, diazepam had limited impact on the other behavioral effects of δ⁹-THC. Conclusions: These results suggest that the GABA_A receptor subtype has minimal involvement in the interoceptive effects of δ⁹-THC, and by extension cannabis, in humans.

Original language	English
Pages (from-to)	141-148
Number of pages	8
Journal	Drug and Alcohol Dependence
Volume	143
Issue number	1
DOIs	https://doi.org/10.1016/j.drugalcdep.2014.07.016
State	Published - 2014

Bibliographical note

Funding Information:
This research and the preparation of this manuscript were supported by grants awarded to Dr. Joshua Lile ( National Institute on Drug Abuse grants K02 DA031766 and R01 DA025605 ) as well as the University of Kentucky Center for Clinical and Translational Science UL1TR000117 ( National Center for Advancing Translational Sciences grant UL1TR000117 ). These funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

Publisher Copyright:
© 2014 Elsevier Ireland Ltd.

Keywords

Cardiovascular
Digit-symbol-substitution task
Drug discrimination
Marijuana
Repeated acquisition task
Subjective effects

ASJC Scopus subject areas

Toxicology
Pharmacology
Psychiatry and Mental health
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.drugalcdep.2014.07.016

Cite this

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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 δ9-tetrahydrocannabinol (δ9-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 δ9-THC using pharmacologically selective drug-discrimination procedures. Methods: Ten cannabis users learned to discriminate 30mg oral δ9-THC from placebo and then received diazepam (5 and 10mg), δ9-THC (5, 15 and 30mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected. Results: δ9-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 δ9-THC discriminative stimulus or alter the δ9-THC discrimination dose-response function. Similarly, diazepam had limited impact on the other behavioral effects of δ9-THC. Conclusions: These results suggest that the GABAA receptor subtype has minimal involvement in the interoceptive effects of δ9-THC, and by extension cannabis, in humans.",

keywords = "Cardiovascular, Digit-symbol-substitution task, Drug discrimination, Marijuana, Repeated acquisition task, Subjective effects",

author = "Lile, {Joshua A.} and Kelly, {Thomas H.} and Hays, {Lon R.}",

note = "Funding Information: This research and the preparation of this manuscript were supported by grants awarded to Dr. Joshua Lile ( National Institute on Drug Abuse grants K02 DA031766 and R01 DA025605 ) as well as the University of Kentucky Center for Clinical and Translational Science UL1TR000117 ( National Center for Advancing Translational Sciences grant UL1TR000117 ). These funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. Publisher Copyright: {\textcopyright} 2014 Elsevier Ireland Ltd.",

year = "2014",

doi = "10.1016/j.drugalcdep.2014.07.016",

language = "English",

volume = "143",

pages = "141--148",

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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.

N1 - Funding Information: This research and the preparation of this manuscript were supported by grants awarded to Dr. Joshua Lile ( National Institute on Drug Abuse grants K02 DA031766 and R01 DA025605 ) as well as the University of Kentucky Center for Clinical and Translational Science UL1TR000117 ( National Center for Advancing Translational Sciences grant UL1TR000117 ). These funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. Publisher Copyright: © 2014 Elsevier Ireland Ltd.

PY - 2014

Y1 - 2014

N2 - Background: Our previous research suggested the involvement of γ-aminobutyric acid (GABA), in particular the GABAB receptor subtype, in the interoceptive effects of δ9-tetrahydrocannabinol (δ9-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 δ9-THC using pharmacologically selective drug-discrimination procedures. Methods: Ten cannabis users learned to discriminate 30mg oral δ9-THC from placebo and then received diazepam (5 and 10mg), δ9-THC (5, 15 and 30mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected. Results: δ9-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 δ9-THC discriminative stimulus or alter the δ9-THC discrimination dose-response function. Similarly, diazepam had limited impact on the other behavioral effects of δ9-THC. Conclusions: These results suggest that the GABAA receptor subtype has minimal involvement in the interoceptive effects of δ9-THC, and by extension cannabis, in humans.

AB - Background: Our previous research suggested the involvement of γ-aminobutyric acid (GABA), in particular the GABAB receptor subtype, in the interoceptive effects of δ9-tetrahydrocannabinol (δ9-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 δ9-THC using pharmacologically selective drug-discrimination procedures. Methods: Ten cannabis users learned to discriminate 30mg oral δ9-THC from placebo and then received diazepam (5 and 10mg), δ9-THC (5, 15 and 30mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected. Results: δ9-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 δ9-THC discriminative stimulus or alter the δ9-THC discrimination dose-response function. Similarly, diazepam had limited impact on the other behavioral effects of δ9-THC. Conclusions: These results suggest that the GABAA receptor subtype has minimal involvement in the interoceptive effects of δ9-THC, and by extension cannabis, in humans.

KW - Cardiovascular

KW - Digit-symbol-substitution task

KW - Drug discrimination

KW - Marijuana

KW - Repeated acquisition task

KW - Subjective effects

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