de Wit H, Johanson C E, Uhlenhuth E H
Curr Med Res Opin. 1984;8 Suppl 4:48-59. doi: 10.1185/03007998409109544.
A series of studies has been carried out using a choice procedure to investigate the reinforcing properties of benzodiazepines in adult volunteer subjects. Amphetamine and other drugs with undisputed dependence potential are clearly preferred by the majority of subjects using this procedure. However, diazepam has not been found to be an effective reinforcer across a range of doses, using various subject populations and under different experimental conditions. In the present study, lorazepam, a benzodiazepine with a shorter half-life than diazepam, was tested. Twelve normal volunteer subjects were tested in 4 separate experiments in which three doses of lorazepam (0.5, 1.0 and 2.0 mg) were each compared to placebo, and in a separate experiment, 1.0 mg lorazepam was compared to 5.0 mg diazepam. Subjects showed no preference between 0.5 mg lorazepam and placebo or between 1.0 mg lorazepam and 5.0 mg diazepam, but at the 1.0 and 2.0 mg doses of lorazepam they showed a clear preference for placebo. Subjective effects of the drugs were also monitored, and showed changes consistent with the anxiolytic and sedative effects of the drugs. The duration of the effects of lorazepam was unexpectedly long (as long as 6 hours), so the question whether a shorter-acting benzodiazepine would be a more effective reinforcer in this situation remains unanswered.
已经开展了一系列研究，采用选择程序来调查苯二氮䓬类药物在成年志愿者中的强化特性。使用该程序时，大多数受试者明显更倾向于苯丙胺和其他具有无可争议成瘾潜力的药物。然而，在使用不同受试者群体并在不同实验条件下，未发现地西泮在一系列剂量下是一种有效的强化物。在本研究中，对一种半衰期比地西泮短的苯二氮䓬类药物劳拉西泮进行了测试。12名正常志愿者受试者在4个独立实验中接受了测试，在这些实验中，将三种剂量的劳拉西泮（0.5、1.0和2.0毫克）分别与安慰剂进行比较，并且在一个单独实验中，将1.0毫克劳拉西泮与5.0毫克地西泮进行比较。受试者在0.5毫克劳拉西泮与安慰剂之间或1.0毫克劳拉西泮与5.0毫克地西泮之间没有表现出偏好，但在1.0毫克和2.0毫克剂量的劳拉西泮下，他们明显更倾向于安慰剂。还监测了药物的主观效应，其显示出与药物的抗焦虑和镇静作用一致的变化。劳拉西泮的效应持续时间出人意料地长（长达6小时），因此在这种情况下作用时间更短的苯二氮䓬类药物是否会是一种更有效的强化物这一问题仍未得到解答。
