Separate and combined effects of the GABA B agonist baclofen and Δ 9-THC in humans discriminating Δ 9-THC

摘要

Background: Our previous research with the GABA reuptake inhibitor tiagabine suggested the involvement GABA in the interoceptive effects of Δ 9-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 Δ 9-THC using pharmacologically specific drug-discrimination procedures. Methods: Eight cannabis users learned to discriminate 30mg oral Δ 9-THC from placebo and then received baclofen (25 and 50mg), Δ 9-THC (5, 15 and 30mg) 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), elevated heart rate and impaired rate and accuracy on a psychomotor performance task. Baclofen alone (50mg) substituted for the Δ 9-THC discriminative stimulus, and both baclofen doses shifted the discriminative-stimulus effects of Δ 9-THC leftward/upward. Similar results were observed on other cannabinoid-sensitive outcomes, although baclofen generally did not engender Δ 9-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 Δ 9-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 Δ 9-THC, and by extension cannabis, in humans.