Effect of rate of administration on subjective and physiologica effects of intravenous cocaine in humans
Effect of rate of administration on subjective and physiologica effects of intravenous cocaine in humans
复制标题
DOI：
10.1016/j.drugalcdep.2005.08.004
复制
发表时间：
2006-03-15
影响因子：
4.2
通讯作者：
Gorelick, DA
中科院分区：
文献类型：
--
作者：
Nelson, RA;Boyd, SJ;Gorelick, DA
精神药物作用速率假说认为，药物到达大脑并开始起作用的速度越快，其强化效应和滥用可能性就越大。先前一项使用单一剂量可卡因的人体研究证实了主观反应的速率假设，但没有发现心血管反应的速率效应。我们采用双盲、安慰剂对照、剂量递增设计，对17名有经验的可卡因使用者（7名[所有男性]提供了完整的数据；6名只参加了1-2次治疗）分别在3次服药时间（10、25、50 mg）和注射时间（10、30、60 s）中给予静脉注射可卡因，评估了速率假设。给药后测量I - It的主观效应（100毫米视觉模拟量表），心率、血压、阳性（如：急促、高）和阴性（如：感觉不好、焦虑）。通过重复测量混合线性回归分析评估从基线到峰值的峰值变化，以及时间-反应曲线下的面积，允许使用所有受试者的所有会话的数据，包括未完成的数据。浓度（mg）和输注速率（mg/s）对大多数主观和心血管变量均有显著影响。相互作用分析表明，剂量的影响大于速率的影响。速率对积极主观效应的影响大于对消极主观效应或心血管变量的影响。这些发现为速率假说提供了支持，因为它适用于人类静脉注射可卡因的主观和心血管效应。2005爱思唯尔爱尔兰有限公司版权所有。
The rate hypothesis of psychoactive drug action holds that the faster a drug reaches the brain and starts to act, the greater its reinforcing effects and abuse liability. A previous human study using a single cocaine dose confirmed the rate hypothesis for subjective responses, but found no rate effect on cardiovascular responses. We evaluated the rate hypothesis in 17 experienced cocaine users (7 [all men] provided complete data; 6 participated in only 1-2 sessions) by administering IV cocaine at each of three closes (10, 25, 50 mg) and injection durations (10, 30, 60 s) in a double-blind, placebo-controlled, escalating dose design. Heart rate, blood pressure, and Positive (e.g., rush, high) and negative (e.g., feel bad, anxious) Subjective effects (100-mm visual analogue scales) were measured for I It after dosing. Peak change from baseline, time to peak, and area under the time-response curve were evaluated with repeated measures mixed linear regression analyses, allowing use of data from all sessions for all subjects, including non-completers. Both close (mg) and infusion rate (mg/s) significantly influenced most subjective and cardiovascular variables. Analysis of the interaction suggested that dose had a stronger impact than rate. Rate had a stronger influence on positive subjective effects than on negative Subjective effects or cardiovascular variables. These findings provide Support for the rate hypothesis as it applies to both subjective and cardiovascular effects of IV cocaine administration in humans. (C) 2005 Elsevier Ireland Ltd. All rights reserved.