Influence of tiagabine maintenance on cannabis effects and related behaviors in daily cannabis users

No medications are approved for cannabis use disorder (CUD). Gamma-aminobutyric acid (GABA) reuptake is modulated by cannabinoid (CB) receptor agonists, and there are shared effects between CB agonists and the GABA reuptake inhibitor tiagabine. This overlapping neuropharmacology suggested that tiagabine might be useful for CUD. The study determined the ability of tiagabine maintenance to reduce cannabis selfadministration using a placebo-controlled, double-blind, counterbalanced, within-subjects design. Nontreatment-seeking daily cannabis users (N = 12; 3 female, 9 male) completed two 12-day outpatient maintenance phases (0 or 12 mg of tiagabine/day). Each phase consisted of a safety session, 7 maintenance days, and 4 experimental sessions. During experimental sessions, maintenance continued and participants completed two 2-day blocks of sampling and self-administration sessions to determine the reinforcing effects of smoked cannabis (0% and 5.9% Δ9-tetrahydrocannabinol). Naturalistic cannabis use, the subjective, performance and physiological response to cannabis, as well as side effects, sleep quality, craving, other self-reported substance use, and observer ratings were also measured. Cannabis functioned as a reinforcer and produced prototypical effects (e.g., increased heart rate and ratings of "high"), but tiagabine generally did not impact the effects of cannabis, or alter naturalistic use. Furthermore, tiagabine produced small, but significant, increases on 2 subscales of a Marijuana Craving Questionnaire, and reductions in both the amount of time slept in the past 24 hr and ratings of positive mood upon awakening. These human laboratory results from a sample of nontreatment-seeking cannabis users do not support the potential efficacy of 12 mg of tiagabine as a stand-alone pharmacotherapy for CUD.