Effects of baclofen on cocaine self-administration: Opioid- and nonopioid-dependent volunteers
Effects of baclofen on cocaine self-administration: Opioid- and nonopioid-dependent volunteers
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DOI：
10.1038/sj.npp.1300999
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发表时间：
2006-08-01
影响因子：
7.6
通讯作者：
Foltin, Richard W.
中科院分区：
文献类型：
--
作者：
Haney, Margaret;Hart, Carl L.;Foltin, Richard W.
临床前和临床研究表明，GABA(B)受体激动剂选择性地减少可卡因的使用。人类巴氯芬和可卡因相互作用的行为机制尚不清楚，其对可卡因和美沙酮同时依赖的个体的影响也尚未确定。本研究的目的是确定维持巴氯芬对可卡因的强化效应、主观效应、情绪和可卡因渴望在可卡因依赖志愿者开始使用可卡因前后的影响，这些志愿者同时存在阿片类药物依赖。非寻求治疗的志愿者（10名非阿片类药物依赖者，7名维持美沙酮），在住院研究单位居住21天，每剂量巴氯芬（0、30、60 mg / po）维持7天。分别在每一种巴氯芬维持状态的第3-4天和第6-7天测定两次吸食可卡因的剂量-反应曲线（0、12、25、50 mg）。可卡因疗程从一个样本试验开始，参与者吸食该疗程可用剂量的可卡因，然后进行五个选择试验，参与者在吸食可用剂量的可卡因或获得一张5美元的商品代金券之间做出选择。结果显示，在非美沙酮组中，巴氯芬（60毫克）减少了低剂量可卡因（12毫克）的自我给药。在美沙酮组，巴氯芬减少了对可卡因的渴望。在两组中，巴氯芬都降低了可卡因对心率的影响。巴氯芬并没有改变两组可卡因强烈的主观效应（如“高”、“刺激”）。这项实验室研究的结果与临床证据一致，表明巴氯芬减少了寻求可卡因依赖治疗的非阿片类药物依赖患者的可卡因使用。在美沙酮维持的参与者中不同的效果模式表明巴氯芬可能对阿片类药物依赖的可卡因使用者无效。
Preclinical and clinical studies suggest that GABA(B) receptor agonists selectively decrease cocaine use. The behavioral mechanism for the interaction between baclofen and cocaine in humans is not known, nor have its effects been characterized in individuals dependent on both cocaine and methadone, The objective of this study is to determine how maintenance on baclofen influences smoked cocaine's reinforcing and subjective effects, mood and cocaine craving prior to and after the initiation of cocaine use in cocaine-dependent volunteers with and without concurrent opioid dependence, Nontreatment-seeking volunteers (10 nonopioid dependent; seven methadone maintained), residing on an in-patient research unit for 2 1 days, were maintained on each baclofen dose (0, 30, 60 mg po) for 7 days. A smoked cocaine dose-response curve (0, 12, 25, 50 mg) was determined twice: on days 3-4 and days 6-7 of each baclofen maintenance condition. Cocaine sessions began with a sample trial, when participants smoked the cocaine dose available that session, and five choice trials, when participants chose between smoking the available cocaine dose or receiving one $5 merchandise voucher. The results show that in the nonmethadone group, baclofen (60 mg) decreased self-administration of a low cocaine dose (12 mg). In the methadone group, baclofen decreased craving for cocaine. In both groups, baclofen decreased cocaine's effects on heart rate. Baclofen did not alter cocaine's robust subjective effects (eg 'High,' 'Stimulated') for either group, The results from this laboratory study appear consistent with clinical evidence showing that baclofen decreases cocaine use in nonopioid-dependent patients seeking treatment for cocaine dependence. The distinct pattern of effects in methadone-maintained participants suggests baclofen may not be effective in opioid-dependent cocaine users.