Adaptive Clinical Trial of Adenosine A2a Antagonist in Cocaine Dependence

腺苷 A2a 拮抗剂治疗可卡因依赖的适应性临床试验

• 批准号: 8004209
• 负责人: JOY Marie SCHMITZ
• 金额: --
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8004209
• 关键词: Acute; Address; Adenosine; Adenosine A2A Receptor; Affect; Affective; Agonist; Alcohols; Anterior; Attention; Attenuated; Behavior Control; Behavioral; Behavioral inhibition; Biochemical; Brain region; CNR1 gene; Cannabinoids; Cardiovascular system; Chronic; Clinical Trials; Cocaine; Cocaine Dependence; Cocaine Users; Cognitive; Conflict (Psychology); Data; Decision Making; Development; Dextroamphetamine; Dopamine; Dopamine Agonists; Dopamine D2 Receptor; Dopamine Receptor; Dose; Functional disorder; Hippocampus (Brain); Homeostasis; Human; Impairment; Impulsivity; Individual; Intoxication; Marijuana; Marijuana Smoking; Measurable; Measures; Mediating; Methods; Midbrain structure; Modeling; Monitor; Neurologic Manifestations; Nucleus Accumbens; Patients; Performance; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physiological; Physiological Processes; Placebo Effect; Placebos; Play; Process; Property; Psychological reinforcement; Psychopharmacology; Receptor Activation; Regulation; Relapse; Relative (related person); Research; Reversal Learning; Role; Short-Term Memory; Structure; Substance abuse problem; System; Tachycardia; Task Performances; Techniques; Therapeutic Intervention; Training; Treatment Efficacy; Urine; Withdrawal; Work; addiction; allostasis; base; behavioral deficiency; cocaine use; cognitive control; design; dopamine system; drug discrimination; flexibility; improved; marijuana abuser; marijuana user; monoamine; neurotransmission; novel; psychopharmacologic; receptor; relating to nervous system; research study; response; reward processing

Chronic cocaine use may produce disruption of monoamine systems (including dopamine). This may in turn contribute to measurable dysfunction in important cognitive and behavioral processes. Pharmacotherapy with stimulants that enhance dopamine (DA) function has shown efficacy in treating cocaine dependence and improving behavioral function ~ supporting the notion that these processes are related. In the development of novel pharmacotherapies for cocaine dependence, an important step is a full understanding of the.psychopharmacological properties of potential medications for cocaine dependence, including subjective, physiological, discriminative and behavioral effects. Selective adenosine (A2A) receptor antagonists may play a key role in the modulation of DA neurotransmission by indirectly enhancing DA receptor activation. Additionally, A2A antagonists inhibit cannabinoid CBI receptor activation, suggesting a potential mechanism for reducing concurrent marijuana use in cocaine dependent patients. A2A antagonists may provide additional benefit on concurrent marijuana use in cocaine dependence, as dual cocaine-marijuana users present unique treatment challenges. This project proposes to evaluate the novel A2A antagonist SYN 115. Its stimulant-like effects may help with affective and behavioral deficiencies related to (a) DA depletion and (b) DA-CB1 interactions. Accordingly, the project aims to characterize the psychopharmacology of SYN115 in individuals with cocaine dependence, cocaine dependence with concurrent marijuana use, and controls. Employing both acute and chronic dosing designs, three experiments will be conducted using well-established psychopharmacological methods in order to characterize dose-response relationships. A mixed-model strategy will be utilized to (a) leverage the power of within-subject, repeated measures designs, and (b) compare cocaine dependent and healthy matched-control subjects. Measures will include drug discrimination, subjective effects, cardiovascular effects, behavioral inhibition (impulsivity), working memory, reversal learning, and decision making. These data will compliment and provide valuable information to our parallel clinical trials using these agents to treat cocaine dependence

慢性可卡因使用可能会导致单胺系统（包括多巴胺）的破坏。反过来可能 在重要的认知和行为过程中有助于可测量的功能障碍。药物治疗 增强多巴胺功能（DA）功能的兴奋剂显示出在治疗可卡因依赖性方面的功效 并改善行为函数〜支持这些过程相关的观念。在 开发可卡因依赖的新型药物疗法，一个重要的步骤是完全理解 潜在药物可卡因依赖性药物的精神病学特性，包括 主观，生理，歧视和行为影响。 Selective adenosine (A2A) receptor antagonists may play a key role in the modulation of DA 通过间接增强DA受体激活的神经传递。另外，A2A拮抗剂抑制 大麻素CBI受体激活，提出了减少并发大麻的潜在机制 用于可卡因依赖患者。 A2A拮抗剂可能会给并发大麻提供额外的好处 在可卡因依赖性中使用，作为双可卡因 - 马里瓜娜（Marijuana）的使用者提出了独特的治疗挑战。 该项目建议评估新型A2A拮抗剂SYN 115。其刺激性效果可能有助于 与（a）DA耗竭和（b）DA-CB1相互作用有关的情感和行为缺陷。因此， 该项目旨在表征可卡因个体中Syn115的心理药理学 依赖性，可卡因与并发大麻的使用和控制。同时使用急性和 长期剂量设计，将使用良好的心理药理学进行三个实验 为了表征剂量反应关系的方法。混合模型策略将用于（a） 利用受试者内部的功能，重复的措施设计以及（b）比较可卡因依赖性和 健康匹配的控制受试者。措施将包括药物歧视，主观影响， 心血管效应，行为抑制（冲动），工作记忆，逆转学习和决策 制作。这些数据将使用 这些药物治疗可卡因依赖性