Separate and combined effects of the GABA reuptake inhibitor tiagabine and Δ9-THC in humans discriminating Δ9-THC.

Abstract

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. 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. 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. 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.