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A human laboratory pilot study with baclofen in alcoholic individuals

机译：用酒精个体中的Baclofen进行人力实验室试验研究

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Preclinical and clinical studies show that the GABAB receptor agonist baclofen may represent a pharmacotherapy for alcohol dependence (AD). However, the mechanisms by which baclofen affects drinking are not well characterized; thus this pilot study investigated possible baclofen's biobehavioral mechanisms. The design was a double-blind controlled randomized human laboratory pilot study. Fourteen non-treatment seeking alcohol-dependent heavy drinking subjects received either baclofen 10 mg t.i.d. or an active placebo (cyproheptadine 2 mg t.i.d., to control for sedation) for a 7-day period. At day 8, participants performed an alcohol cue-reactivity (CR) followed by an alcohol self-administration (ASA). Additionally, we explored possible moderators that might guide future larger studies, i.e. anxiety, family history and onset of alcoholism, and D4 dopamine receptor (DRD4) and 5-HTTLPR polymorphisms. The main results were a significant effect of baclofen for increasing stimulation (p =.001) and sedation (p .01). Furthermore, when drinking during the ASA and the 2 days before was analyzed as a composite variable, there was a significant effect of baclofen to reduce alcohol consumption (p .01). As for the exploratory analyses, baclofen's effects to increase alcohol sedation and to reduce alcohol consumption were limited to those individuals with DRD4 ?? 7 repeats (DRD4L). Yet, baclofen's effects on alcohol consumption were also moderated by 5-HTTLPR LL genotype. In conclusion, baclofen's ability to reduce alcohol drinking may be related to its effects on the biphasic effects of alcohol, but larger studies are needed to confirm these preliminary findings. ? 2012 Elsevier Inc.
机译：临床前和临床研究表明，纳布夫受体激动剂Baclofen可以代表醇依赖（AD）的药物疗法。然而，Baclofen影响饮酒的机制并不具备很好的表征;因此，该试点研究调查了可能的Baclofen的生物侵入机制。该设计是一项双盲控制随机人力实验室试验研究。 44个非治疗饲料依赖酒精依赖性的重饮用受试者，接受Baclofen 10 mg T.I.D。或者活性安慰剂（Cyproheptaine 2 mg T.I.D.，用于控制镇静）7天。在第8天，参与者进行了酒精提示反应性（CR），然后进行酒精自我给药（ASA）。此外，我们还探讨了可能导致未来更大研究的可能主持人，即焦虑，家族史和酗酒，D4多巴胺受体（DRD4）和5-HTTLPR多态性。主要结果是Baclofen用于增加刺激（P = .001）和镇静（P <.01）的显着效果。此外，当在ASA期间饮用和在2天之前被分析为复合变量时，Baclofen患有显着的效果以降低醇消耗（P <.01）。至于探索性分析，Baclofen对增加酒精镇静和减少酒精消费的影响仅限于DRD4的人7重复（DRD4L）。然而，Baclofen对醇消耗的影响也受到5-HTTLPR LL基因型的调节。总之，Baclofen减少酒精饮酒的能力可能与其对酒精双色效应的影响有关，但需要更大的研究来确认这些初步结果。还2012年elsevier公司

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