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Separate and combined effects of the GABA(B) agonist baclofen and Δ9-THC in humans discriminating Δ9-THC.
Drug Alcohol Depend. 2012 Nov 01; 126(1-2):216-23.DA

Abstract

BACKGROUND

Our previous research with the GABA reuptake inhibitor tiagabine suggested the involvement GABA in the interoceptive effects of Δ9-THC. The aim of the present study was to determine the potential involvement of the GABA(B) receptor subtype by assessing the separate and combined effects of the GABA(B)-selective agonist baclofen and Δ9-THC using pharmacologically specific drug-discrimination procedures.

METHODS

Eight cannabis users learned to discriminate 30 mg oral Δ9-THC from placebo and then received baclofen (25 and 50mg), Δ9-THC (5, 15 and 30 mg) 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), elevated heart rate and impaired rate and accuracy on a psychomotor performance task. Baclofen alone (50 mg) substituted for the Δ9-THC discriminative stimulus, and both baclofen doses shifted the discriminative-stimulus effects of Δ9-THC leftward/upward. Similar results were observed on other cannabinoid-sensitive outcomes, although baclofen generally did not engender Δ9-THC-like subjective responses when administered alone.

CONCLUSIONS

These results suggest that the GABA(B) receptor subtype is involved in the abuse-related effects of Δ9-THC, and that GABA(B) receptors were responsible, at least in part, for the effects of tiagabine-induced elevated GABA on cannabinoid-related behaviors in our previous study. Future research should test GABAergic compounds selective for other GABA receptor subtypes (i.e., GABA(A)) to determine the contribution of the different GABA receptors in the effects of Δ9-THC, and by extension cannabis, in humans.

Authors+Show Affiliations

Department of Behavioral Science, University of Kentucky, College of Medicine, Medical Behavioral Sciences Building, Lexington, KY 40536-0086, USA. jalile2@email.uky.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22699093

Citation

Lile, Joshua A., et al. "Separate and Combined Effects of the GABA(B) Agonist Baclofen and Δ9-THC in Humans Discriminating Δ9-THC." Drug and Alcohol Dependence, vol. 126, no. 1-2, 2012, pp. 216-23.
Lile JA, Kelly TH, Hays LR. Separate and combined effects of the GABA(B) agonist baclofen and Δ9-THC in humans discriminating Δ9-THC. Drug Alcohol Depend. 2012;126(1-2):216-23.
Lile, J. A., Kelly, T. H., & Hays, L. R. (2012). Separate and combined effects of the GABA(B) agonist baclofen and Δ9-THC in humans discriminating Δ9-THC. Drug and Alcohol Dependence, 126(1-2), 216-23. https://doi.org/10.1016/j.drugalcdep.2012.05.023
Lile JA, Kelly TH, Hays LR. Separate and Combined Effects of the GABA(B) Agonist Baclofen and Δ9-THC in Humans Discriminating Δ9-THC. Drug Alcohol Depend. 2012 Nov 1;126(1-2):216-23. PubMed PMID: 22699093.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Separate and combined effects of the GABA(B) agonist baclofen and Δ9-THC in humans discriminating Δ9-THC. AU - Lile,Joshua A, AU - Kelly,Thomas H, AU - Hays,Lon R, Y1 - 2012/06/13/ PY - 2012/04/11/received PY - 2012/05/14/revised PY - 2012/05/17/accepted PY - 2012/6/16/entrez PY - 2012/6/16/pubmed PY - 2013/4/9/medline SP - 216 EP - 23 JF - Drug and alcohol dependence JO - Drug Alcohol Depend VL - 126 IS - 1-2 N2 - BACKGROUND: Our previous research with the GABA reuptake inhibitor tiagabine suggested the involvement GABA in the interoceptive effects of Δ9-THC. The aim of the present study was to determine the potential involvement of the GABA(B) receptor subtype by assessing the separate and combined effects of the GABA(B)-selective agonist baclofen and Δ9-THC using pharmacologically specific drug-discrimination procedures. METHODS: Eight cannabis users learned to discriminate 30 mg oral Δ9-THC from placebo and then received baclofen (25 and 50mg), Δ9-THC (5, 15 and 30 mg) 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), elevated heart rate and impaired rate and accuracy on a psychomotor performance task. Baclofen alone (50 mg) substituted for the Δ9-THC discriminative stimulus, and both baclofen doses shifted the discriminative-stimulus effects of Δ9-THC leftward/upward. Similar results were observed on other cannabinoid-sensitive outcomes, although baclofen generally did not engender Δ9-THC-like subjective responses when administered alone. CONCLUSIONS: These results suggest that the GABA(B) receptor subtype is involved in the abuse-related effects of Δ9-THC, and that GABA(B) receptors were responsible, at least in part, for the effects of tiagabine-induced elevated GABA on cannabinoid-related behaviors in our previous study. Future research should test GABAergic compounds selective for other GABA receptor subtypes (i.e., GABA(A)) to determine the contribution of the different GABA receptors in the effects of Δ9-THC, and by extension cannabis, in humans. SN - 1879-0046 UR - https://www.unboundmedicine.com/medline/citation/22699093/Separate_and_combined_effects_of_the_GABA_B__agonist_baclofen_and_Δ9_THC_in_humans_discriminating_Δ9_THC_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0376-8716(12)00186-X DB - PRIME DP - Unbound Medicine ER -