EXPERIMENTAL ANALYSIS OF SEDATIVE/STIMULANT ABUSE

镇静/兴奋剂滥用的实验分析

• 批准号: 3208667
• 负责人: Roland R Griffiths
• 金额: $ 38.52万
• 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/3208667
• 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.

建议对有吸毒史和正常情况的受试者进行研究。 受试者调查表现障碍、主观影响和 抗焦虑镇静药物的强化作用。一系列 实验将评估抗焦虑-镇静药物在 有镇静剂滥用史的志愿者将居住在 住院研究病房。这些研究将提供详细的剂量效应， 一系列衡量标准中的时间进程和相对效力数据。 主观量表和行为选择比较也将提供 关于增强效果差异的信息。具体地说，四个 实验将比较一系列剂量的劳拉西潘和 一系列剂量的甲基普兰、咪达唑仑、氟硝西潘和几种新的 抗焦虑药。另外四项实验将延长先前的剂量效应 戊巴比妥、苯海拉明、甲氨基甲酚和丁螺环酮的研究 论滥用责任主观衡量标准之间的关系 (例如对喜好的评分)和药物选择(相对于安慰剂和劳拉西潘) 此外，还将研究反复接触毒品的情况 影响喜好和选择的评分。同时推出的一系列非住宅类 实验将检验Low的区分和强化作用。 以及中等剂量的苯二氮卓类药物。其中一组研究将是 在没有吸毒史的受试者中进行检查 苯二氮类药物的鉴别作用。这些研究将确定 鉴别敏感度阈值，药理学检查 特异性，以及丁螺环酮的交叉泛化，表征了 慢性服用苯二氮卓类药物(耐受性)的影响 歧视，并确定歧视培训对 苯二氮类药物的增强和其他作用。最后一组研究 将操作苯二氮卓类药物的剂量和任务难度扩大 先前的研究表明，苯二氮卓类药物可以增强 受背景行为偶发事件的影响。人们对……感到担忧 滥用和滥用苯二氮卓类抗焦虑镇静药物，即 广泛开出的精神药物。最新研究进展 在苯二氮卓类药理学中提高解离的可能性 这些药物的滥用和依赖活性与其他行为和 治疗行动。这项研究将提供关于 行为和药理学作用机制及相关滥用 这些化合物的责任。这应该有助于努力发展 潜力降低的新型抗焦虑镇静化合物 对于性能损害和滥用。更广泛地说，数据将 有助于理解安非他明-镇静剂药物滥用和意志 最终有助于发展改进的预防、控制和 治疗程序。