Tags

Type your tag names separated by a space and hit enter

Separate and combined effects of the GABA reuptake inhibitor tiagabine and Δ9-THC in humans discriminating Δ9-THC.
Drug Alcohol Depend. 2012 Apr 01; 122(1-2):61-9.DA

Abstract

BACKGROUND

The involvement of non-cannabinoid neurotransmitter systems in the abuse-related behavioral effects of cannabis has not been well characterized in humans. GABAergic drugs have overlapping effects with cannabis and Δ(9)-tetrahydrocannabinol (Δ(9)-THC) on certain behavioral measures, but those measures lack the specificity to draw conclusions regarding the involvement of GABA in cannabinoid effects. The aim of this study was to assess the separate and combined effects of the GABA reuptake inhibitor tiagabine and Δ(9)-THC using more pharmacologically specific drug-discrimination procedures.

METHODS

Eight cannabis users learned to discriminate 30 mg oral Δ(9)-THC from placebo and then received tiagabine (6 and 12 mg), 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 produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug), elevated heart rate and impaired rate and accuracy on psychomotor performance tasks. The higher tiagabine dose substituted for the Δ(9)-THC discriminative stimulus and engendered subjective and performance-impairing effects that overlapped with those of Δ(9)-THC when administered alone. In combination, tiagabine shifted the discriminative-stimulus effects of Δ(9)-THC leftward/upward and enhanced Δ(9)-THC effects on other outcomes.

CONCLUSIONS

These results indicate that GABA is involved in the clinical effects of Δ(9)-THC, and by extension, cannabis. Future studies should test selective GABAergic compounds to determine which receptor subtype(s) are responsible for the effects observed when combined with cannabinoids.

Authors+Show Affiliations

Department of Behavioral Science, University of Kentucky College of Medicine, United States.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21975195

Citation

Lile, Joshua A., et al. "Separate and Combined Effects of the GABA Reuptake Inhibitor Tiagabine and Δ9-THC in Humans Discriminating Δ9-THC." Drug and Alcohol Dependence, vol. 122, no. 1-2, 2012, pp. 61-9.
Lile JA, Kelly TH, Hays LR. Separate and combined effects of the GABA reuptake inhibitor tiagabine and Δ9-THC in humans discriminating Δ9-THC. Drug Alcohol Depend. 2012;122(1-2):61-9.
Lile, J. A., Kelly, T. H., & Hays, L. R. (2012). Separate and combined effects of the GABA reuptake inhibitor tiagabine and Δ9-THC in humans discriminating Δ9-THC. Drug and Alcohol Dependence, 122(1-2), 61-9. https://doi.org/10.1016/j.drugalcdep.2011.09.010
Lile JA, Kelly TH, Hays LR. Separate and Combined Effects of the GABA Reuptake Inhibitor Tiagabine and Δ9-THC in Humans Discriminating Δ9-THC. Drug Alcohol Depend. 2012 Apr 1;122(1-2):61-9. PubMed PMID: 21975195.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Separate and combined effects of the GABA reuptake inhibitor tiagabine and Δ9-THC in humans discriminating Δ9-THC. AU - Lile,Joshua A, AU - Kelly,Thomas H, AU - Hays,Lon R, Y1 - 2011/10/04/ PY - 2011/04/18/received PY - 2011/08/11/revised PY - 2011/09/07/accepted PY - 2011/10/7/entrez PY - 2011/10/7/pubmed PY - 2012/7/21/medline SP - 61 EP - 9 JF - Drug and alcohol dependence JO - Drug Alcohol Depend VL - 122 IS - 1-2 N2 - BACKGROUND: The involvement of non-cannabinoid neurotransmitter systems in the abuse-related behavioral effects of cannabis has not been well characterized in humans. GABAergic drugs have overlapping effects with cannabis and Δ(9)-tetrahydrocannabinol (Δ(9)-THC) on certain behavioral measures, but those measures lack the specificity to draw conclusions regarding the involvement of GABA in cannabinoid effects. The aim of this study was to assess the separate and combined effects of the GABA reuptake inhibitor tiagabine and Δ(9)-THC using more pharmacologically specific drug-discrimination procedures. METHODS: Eight cannabis users learned to discriminate 30 mg oral Δ(9)-THC from placebo and then received tiagabine (6 and 12 mg), 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 produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug), elevated heart rate and impaired rate and accuracy on psychomotor performance tasks. The higher tiagabine dose substituted for the Δ(9)-THC discriminative stimulus and engendered subjective and performance-impairing effects that overlapped with those of Δ(9)-THC when administered alone. In combination, tiagabine shifted the discriminative-stimulus effects of Δ(9)-THC leftward/upward and enhanced Δ(9)-THC effects on other outcomes. CONCLUSIONS: These results indicate that GABA is involved in the clinical effects of Δ(9)-THC, and by extension, cannabis. Future studies should test selective GABAergic compounds to determine which receptor subtype(s) are responsible for the effects observed when combined with cannabinoids. SN - 1879-0046 UR - https://www.unboundmedicine.com/medline/citation/21975195/Separate_and_combined_effects_of_the_GABA_reuptake_inhibitor_tiagabine_and_Δ9_THC_in_humans_discriminating_Δ9_THC_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0376-8716(11)00398-X DB - PRIME DP - Unbound Medicine ER -