AMLODIPINE TREATMENT FOR COCAINE DEPENDENCE

药物疗法尚未被证明在临床上有效。 可卡因依赖的治疗。有两种研究表明 钙通道拮抗剂有望用于可卡因的治疗 依赖。1)慢性可卡因使用的临床研究有 PET、SPECT和MRI显示多种神经血管改变 大脑的一部分。这些研究表明，糖尿病患者存在功能异常 能量利用和局部脑血流量的减少。一些人 随着赤字的延长，这些赤字的改善已被注意到 戒除可卡因；然而，最近的研究表明，一些人 局部血流变化持续数月。它是 这些神经血管异常可能会降低认知能力 能力，从而减少康复治疗的好处 可卡因依赖，如认知行为疗法(CBT)。钙 经络拮抗剂拮抗脑血管收缩，增强 局部脑血流，并可能导致认知 进步。2)临床前研究表明二氢吡啶型 通道拮抗剂在大鼠脑内有特定的结合部位并发挥作用 在调节多巴胺能强化中的作用。钙通道 拮抗剂可以减少与可卡因相关的行为。一次人体试验 表明钙通道拮抗剂降低了主观性 可卡因的激增和可卡因的快感特性降低。因此，在那里 是动物和人类的证据表明钙通道拮抗剂可能 改善大脑循环，增强认知功能，改变 可卡因的主观有益体验。该协议提出了 评估上市的二氢吡啶钙通道氨氯地平 具有良好安全性的拮抗剂，并已 增强局部脑血流量的作用。与 CBT、氨氯地平和安慰剂的疗效将在160名男性中进行测试 女性，高加索人和非裔美国人。经过筛选和 知情同意后，可卡因依赖者将进入为期两周的 安慰剂期，随后随机至氨氯地平联合治疗12周 CBT或安慰剂加CBT。后续调查将在三个月后进行 治疗结束了。治疗结果将每周两次进行评估 定量尿液药物筛查可卡因和可卡因代谢物， 治疗中的滞留、主观的可卡因渴求和心理测量 认知功能测试。对该代理的评估 有效性和安全性提供了检查 理由是局部脑血流的改善或 钙通道拮抗作用对多巴胺调节机制的影响 将促进可卡因依赖的恢复。

Pharmacotherapies have not proven to be clinically useful in the treatment of cocaine dependence. Two lines of research indicate that calcium channel antagonists are promising in the treatment of cocaine dependence. 1) Clinical studies of chronic cocaine use have demonstrated multiple neurovascular changes on PET, SPECT and MRI scans of the brain. These studies demonstrate functional abnormalities in energy utilization and reductions in regional cerebral blood flow. Some improvement in these deficits have been noted with lengthening abstinence from cocaine; however, recent work indicates that some regional blood flow changes are persistent over many months. It is possible that these neurovascular abnormalities decrease cognitive abilities and thus reduce the benefits of rehabilitative treatment for cocaine dependence such as cognitive-behavioral therapy (CBT). Calcium channel antagonists antagonize cerebral vasoconstriction, enhance regional cerebral blood flow and possibly could lead to cognitive improvement. 2) Preclinical studies indicate that dihydropyridine type channel antagonists have specific binding sites in rat brains and play a role in modulating dopaminergic reinforcement. Calcium channel antagonists reduce cocaine- related behaviors. One human trial demonstrated that a calcium channel antagonist decreased the subjective rush of cocaine and reduced euphoric properties of cocaine. Thus, there is animal and human evidence that calcium channel antagonists may improve cerebral circulation, enhancing cognitive functioning, and alter the subjective rewarding experience of cocaine. This protocol proposes to evaluate amlodipine, a marketed dihydropyridine calcium channel antagonist which has a well-established safety profile and has known effects of enhancing regional cerebral blood flow. In conjunction with CBT, amlodipine versus placebo will be tested for efficacy in 160 males and females, Caucasians and African-Americans. After screening and informed consent, cocaine dependent individuals will enter a two week placebo period followed by randomization to 12 weeks of amlodipine plus CBT or placebo plus CBT. Follow-up will occur three months after treatment ends. Treatment outcome will be measured with twice weekly quantitative urine drug screens for cocaine and cocaine metabolites, retention in treatment,subjective cocaine craving, and psychometric testing of cognitive functions. Evaluation of this agent for effectiveness and safety provides the opportunity to examine the rationale that improvements in regional cerebral blood flow or modulation of dopamine mechanisms through calcium channel antagonism will enhance recovery from cocaine dependence.