Wesley Michael J, Westgate Philip M, Stoops William W, Kelly Thomas H, Hays Lon R, Lile Joshua A
Department of Behavioral Science.
Department of Biostatistics, University of Kentucky College of Public Health.
Exp Clin Psychopharmacol. 2018 Jun;26(3):310-319. doi: 10.1037/pha0000180.
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 self-administration 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. (PsycINFO Database Record
目前尚无药物被批准用于治疗大麻使用障碍（CUD）。γ-氨基丁酸（GABA）再摄取受大麻素（CB）受体激动剂调节，且CB激动剂与GABA再摄取抑制剂噻加宾之间存在共同作用。这种重叠的神经药理学表明噻加宾可能对CUD有用。该研究采用安慰剂对照、双盲、平衡、受试者内设计，确定了噻加宾维持治疗减少大麻自我给药的能力。不寻求治疗的每日大麻使用者（N = 12；3名女性，9名男性）完成了两个为期12天的门诊维持阶段（每天0或12毫克噻加宾）。每个阶段包括一个安全环节、7天的维持期和4个实验环节。在实验环节中，维持治疗继续进行，参与者完成两个为期2天的采样和自我给药环节，以确定吸食大麻（0%和5.9% Δ9-四氢大麻酚）的强化作用。还测量了自然状态下的大麻使用情况、对大麻的主观、行为表现和生理反应，以及副作用、睡眠质量、渴望程度、其他自我报告的物质使用情况和观察者评分。大麻起到了强化物的作用，并产生了典型效果（如心率加快和“兴奋”评分增加），但噻加宾一般不影响大麻的效果，也不改变自然状态下的使用情况。此外，噻加宾在大麻渴望问卷的两个子量表上产生了小但显著的增加，并减少了过去24小时的睡眠时间和醒来时的积极情绪评分。这些来自不寻求治疗的大麻使用者样本的人体实验室结果不支持12毫克噻加宾作为CUD单一药物疗法的潜在疗效。（PsycINFO数据库记录）
