AMLODIPINE TREATMENT FOR COCAINE DEPENDENCE

药物疗法尚未被证明在临床上有用， 治疗可卡因依赖。 两条研究线索表明， 钙通道拮抗剂在可卡因的治疗中是有希望的 依赖 1)长期使用可卡因的临床研究 在PET、SPECT和MRI扫描上显示出多种神经血管改变 的大脑。 这些研究表明， 能量利用和局部脑血流量减少。 一些 随着时间延长， 但最近的研究表明， 局部血流变化持续数月。 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 通道拮抗剂拮抗脑血管收缩，增强 局部脑血流量可能会导致认知障碍 改进. 2)临床前研究表明，二氢吡啶型 通道拮抗剂在大鼠脑中具有特异性结合位点， 调节多巴胺能强化的作用。 钙通道 拮抗剂减少可卡因相关行为。 一次人体试验 表明钙通道拮抗剂降低了主观的 可卡因的快感和减少可卡因的欣快特性。 因此 动物和人类证据表明钙通道拮抗剂可以 改善脑循环，增强认知功能，并改变 可卡因的主观奖励体验。 该协议建议 为了评价市售的二氢吡啶钙通道 拮抗剂，具有明确的安全性特征， 增强局部脑血流量的作用。 结合 将在160名男性中测试CBT、安慰剂与安慰剂的疗效 女性、白人和非裔美国人。 经过筛选和 在知情同意的情况下，可卡因依赖者将进入为期两周的 安慰剂期，随后随机分配至12周的安慰剂+ CBT或安慰剂加CBT。 随访将在三个月后进行 治疗结束。 每周两次测量治疗结局 可卡因和可卡因代谢物的定量尿液药物筛查， 保留治疗，主观可卡因渴望，和心理测量 认知功能测试。 评价该试剂用于 有效性和安全性提供了检查 局部脑血流改善或 通过钙通道拮抗作用调节多巴胺机制 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.