EXPERIMENTAL ANALYSIS OF SEDATIVE/STIMULANT ABUSE

镇静/兴奋剂滥用的实验分析

• 批准号: 3208674
• 负责人: Roland R Griffiths
• 金额: $ 38.78万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1997-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3208674
• 关键词: behavior test; benzodiazepine receptor; benzodiazepines; buspirone; central nervous system stimulants; diphenylhydramine; dosage; drug abuse; drug tolerance; human subject; lorazepam; psychopharmacology; reinforcer; sedative /hypnotic; tranquilizer

Research is proposed in subjects with histories of drug abuse and in normal subjects to investigate performance impairments, subjective effects and reinforcing effects of anxiolytic-sedative drugs. One series of experiments will assess the effects of anxiolytic-sedative drugs in volunteers with histories of sedative drug abuse who will reside on an inpatient research ward. These studies will provide detailed dose-effect, time-course and relative potency data across a wide range of measures. Subjective scales and behavioral choice comparisons will also provide information about differences in reinforcing effects. Specifically, four experiments will compare the effects of a range of doses of lorazepam with a range of doses of methyprylon, midazolam, flunitrazepam and several novel anxiolytics. Four additional experiments will extend previous dose-effect studies with pentobarbital, diphenhydramine, methocarbamol and buspirone by examining the relationship between subjective measures of abuse liability (e.g. rating of liking) and drug choice (relative to placebo and lorazepam) and, furthermore, will examine how repeated exposure to the drug conditions affect ratings of liking and choice. A concurrent series of nonresidential experiments will examine the discriminative and reinforcing effects of low and moderate doses of benzodiazepines. One set of studies will be conducted in subjects without histories of drug abuse to examine discriminative effects of benzodiazepines. These studies will determine thresholds for discriminative sensitivity, examine pharmacological specificity, and cross-generalization with buspirone, characterize the effects of chronic benzodiazepine administration (tolerance) on discrimination, and determine the effects of discrimination training on the reinforcing and other effects of benzodiazepines. A final set of studies will manipulate benzodiazepine dose and degree of task difficulty to extend previous research showing that benzodiazepine reinforcement can be modulated by background behavioral contingencies. There is concern about the misuse and abuse of benzodiazepine anxiolytic-sedative drugs, which are widely prescribed psychotropic medications. Recent research developments in benzodiazepine pharmacology raise the possibility of dissociating the abuse and dependence activity of these drugs from other behavioral and therapeutic actions. this research will provide information about behavioral and pharmacological mechanisms of action and relative abuse liability of these compounds. This should contribute to efforts to develop new classes of anxiolytic-sedative compounds which have reduced potential for performance impairment and abuse. More generally, the data will contribute to an understanding of anziolytic-sedative drug abuse and will ultimately contribute to development of improved prevention, control and treatment procedures.

建议在有药物滥用史的受试者和正常受试者中进行研究。 受试者调查性能障碍，主观影响和 抗焦虑镇静药物的强化作用。 一个系列的 实验将评估抗焦虑镇静药物在 有镇静剂滥用史的志愿者， 住院研究病房 这些研究将提供详细的剂量效应， 时间进程和相对效力数据在广泛的措施。 主观尺度和行为选择比较也将提供 关于强化效果差异的信息。 具体来说，四 实验将比较一系列剂量的劳拉西泮与 一系列剂量的甲基普仑、咪达唑仑、氟硝西泮和几种新的 抗焦虑药 四个额外的实验将扩展先前的剂量效应 戊巴比妥、苯海拉明、美索巴莫和丁螺环酮的研究， 审查滥用责任的主观衡量标准之间的关系 (e.g.喜欢程度）和药物选择（相对于安慰剂和劳拉西泮） 此外，还将研究重复暴露于药物条件下 影响喜好和选择的评分。 一个并行的系列非住宅 实验将检查低的区分和加强效果， 和中等剂量的苯二氮卓类药物 一组研究将是 在没有药物滥用史的受试者中进行检查 苯二氮卓类药物的辨别作用。 这些研究将决定 辨别灵敏度的阈值，检查药理学 特异性，并与丁螺环酮交叉概括，表征了 慢性苯二氮卓类给药（耐受性）对 歧视，并确定歧视培训对 苯二氮卓类药物的强化和其他作用。 最后一组研究 将操纵苯二氮卓类药物的剂量和任务难度程度延长 以前的研究表明，苯二氮卓类药物的强化作用可以 由背景行为偶然性调节。 人们担心 苯二氮卓类抗焦虑镇静药物的误用和滥用， 广泛使用的精神药物 最近的研究动态 在苯二氮卓药理学中， 这些药物的滥用和依赖活动， 治疗作用。 这项研究将提供有关 行为和药理作用机制及相对滥用 这些化合物的责任。 这应有助于努力发展 具有降低的潜力的新型抗焦虑-镇静化合物 因绩效受损和滥用而受到处罚。 更一般地说，数据将 有助于了解抗焦虑镇静药物滥用，并将 最终有助于改进预防、控制和 治疗程序。