Tiagabine for Cocaine Dependence in Methadone Treatment

噻加宾治疗美沙酮治疗中的可卡因依赖

• 批准号: 7228946
• 负责人: Gerardo Gonzalez
• 金额: $ 30.52万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-15 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7228946
• 关键词: 4-Aminobutyrate aminotransferase; Abstinence; Age; Animals; Anxiety; Attenuated; Baclofen; Behavior; Behavior Therapy; Clinical Trials; Cocaine; Cocaine Abuse; Cocaine Dependence; Cognitive Therapy; Consumption; Data; Dopamine; Dose; Double-Blind Method; GABA transporter; GABA-B Receptor; HIV; Hepatitis C; Heroin; Hour; Individual; Institution; Intervention; Label; Methadone; Numbers; Opiate Addiction; Opiates; Opioid; Outcome; Participant; Patient Self-Report; Patients; Personal Satisfaction; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Pilot Projects; Placebo Control; Placebos; Population; Positioning Attribute; Psychotherapy; Randomized; Randomized Clinical Trials; Rate; Relapse; Relative (related person); Reporting; Research; Risk; Role; Safety; Serotonin; Substance abuse problem; Supervision; Symptoms; System; Testing; Training; Treatment Efficacy; Treatment outcome; Urinalysis; Vigabatrin; Week; Withdrawal Symptom; Work; base; day; design; experience; follow-up; gabapentin; gamma-Aminobutyric Acid; inhibitor/antagonist; neurotransmission; preclinical study; psychosocial; reuptake; tiagabine; treatment duration; uptake

DESCRIPTION (provided by applicant): No effective pharmacological treatment for cocaine dependence has yet been developed. Comorbid cocaine dependence among methadone maintained patients interferes with treatment outcomes, and increases the risk of relapse to IV use, which is associated with increased risk for HIV and Hepatitis C. Enhanced GABA eurotransmission appears to attenuate cocaine's reinforcing effects. The objective of this proposal is to examine to what extend will enhancing the GABA system modify cocaine-using behavior and attenuate opiate withdrawal symptoms among newly admitted methadone treated patients. The primary hypothesis is that enhancing the GABA system with a GABA transporter blocker tiagabine we expect to reduce cocaine use and to promote abstinence in cocaine abusing methadone treated patients. The secondary hypothesis is that enhancing the GABA system with a GABA transporter blocker tiagabine we expect to attenuate early opiate withdrawal symptoms in newly admitted methadone treated patients. These hypotheses are formulated based on our pilot studies using the selective GABA re-uptake inhibitor tiagabine. This 14-week double-blind, placebo controlled randomized clinical trial will provide treatment for 120 cocaine and opioid dependent patients. Participants, aged 18-65 years, will be randomized to receive tiagabine 32mg/day, tiagabine 20mg/day or placebo while concurrently receiving treatment with methadone. All participants receive weekly 1-hour individual psychotherapy (Cognitive Behavioral Therapy) with experienced clinicians specifically trained to deliver the therapy and who will receive ongoing supervision. A follow-up at 3 months will allow us to evaluate opioid and cocaine use, and changes in psychosocial adjustment. The primary outcomes will be abstinence rates and reduction in opioid and cocaine use, as assessed by self-report and thrice-weekly urinalyses. The proposed study is expected to provide a better understanding of the role of the selective GABA re-uptake inhibitor tiagabine on cocaine using behavior and treatment of opiate withdrawal symptoms, and will provide valuable information to develop new pharmacological interventions for comorbid cocaine dependence among methadone treated patients.

描述（由申请人提供）：尚未开发出针对可卡因依赖的有效药物治疗方法。美沙酮患者中共存的可卡因依赖会干扰治疗结果，并增加静脉注射复发的风险，这与艾滋病毒和丙型肝炎的风险增加有关。增强的 GABA 欧洲传输似乎会减弱可卡因的增强作用。该提案的目的是研究增强 GABA 系统能在多大程度上改变新入院的美沙酮治疗患者的可卡因使用行为并减轻阿片戒断症状。主要假设是，用 GABA 转运蛋白阻滞剂噻加宾增强 GABA 系统，我们期望减少可卡因的使用并促进可卡因滥用美沙酮治疗患者的戒断。第二个假设是，用 GABA 转运蛋白阻滞剂噻加宾增强 GABA 系统，我们预计可以减轻新入院的美沙酮治疗患者的早期阿片戒断症状。这些假设是根据我们使用选择性 GABA 再摄取抑制剂噻加宾的初步研究制定的。 这项为期 14 周的双盲、安慰剂对照随机临床试验将为 120 名可卡因和阿片类药物依赖患者提供治疗。年龄 18-65 岁的参与者将随机接受噻加宾 32 毫克/天、噻加宾 20 毫克/天或安慰剂，同时接受美沙酮治疗。 所有参与者每周接受 1 小时的个人心理治疗（认知行为治疗），由经过专门培训的经验丰富的临床医生提供治疗，并将接受持续的监督。 3 个月的随访将使我们能够评估阿片类药物和可卡因的使用以及心理社会调整的变化。主要结果将是戒断率以及阿片类药物和可卡因使用的减少，通过自我报告和每周三次的尿液分析进行评估。拟议的研究有望更好地了解选择性 GABA 再摄取抑制剂 tiagabine 对可卡因使用行为和阿片戒断症状治疗的作用，并将为开发新的药物干预措施以治疗美沙酮治疗患者的共病可卡因依赖提供有价值的信息。