Separate and combined effects of the GABAB agonist baclofen and Δ9 -THC in humans discriminating Δ9 -THC

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 GABAB receptor subtype by assessing the separate and combined effects of the GABAB -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 50 mg), 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 GABAB receptor subtype is involved in the abuse-related effects of Δ9 -THC, and that GABAB 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., GABAA ) to determine the contribution of the different GABA receptors in the effects of Δ9 -THC, and by extension cannabis, in humans.