Clinical pharmacology of drugs of abuse and of potential treatment medications

本节研究的是 滥用药物和潜在的治疗药物作为我们的一部分， 评估新疗法的计划。潜在治疗 药物被测试滥用的可能性，并筛选 与滥用药物的相互作用可能具有疗效和/或 安全隐患。研究的第一阶段评估了 丁丙诺啡，一种部分阿片激动剂， 开发用于治疗阿片类药物依赖， 完成尽管SL丁丙诺啡在经验丰富的患者中的安全性 据报道，没有身体依赖的阿片类药物使用者， 剂量高达32毫克，人们对潜在的 丁丙诺啡的急性健康风险，如果转移和使用的IV 给药途径，剂量相当于维持给药所用剂量。 丁丙诺啡采用单盲、双模拟设计 剂量高达16 mg IV和12 mg SL。生命体征和氧 饱和度以及主观和行为效应被监测， 长达72小时。氧含量没有明显变化 饱和，对血压仅有轻微影响。丁丙 积极的主观评价增加， 安慰剂，但这些影响并没有增加，在一个有序的剂量相关 方式结果与天花板效应和部分 激动剂活性静脉注射丁丙诺啡的滥用可能性 似乎随着剂量增加，也没有出现 IV和SL之间滥用潜力的实质性差异 丁丙诺啡在测试剂量。丁丙诺啡似乎也 对心肺影响有上限，安全系数高 当在没有其他药物的情况下通过IV途径给药时。 本节中的其他研究考察了 对人类反应的指导和期望， 精神药物指示和期望已经显示 影响消费水平，药物发挥作用的能力， 它的主观影响，以及其他生理影响， 方面的影响.进一步考察药品说明书的影响 作为回应，娱乐性毒品使用者接受了区分 在两个实验中，75 mg曲哌那明和安慰剂之间 在标准的药物辨别中， 范例参与者被告知，两种药物之一 比其他药物更像镇静剂， 两种药物中的一种更像兴奋剂。 地西泮和安非他明的区别，然后测试， 每个实验。结果表明，设计用于 让参与者对他们会使用的药物类型有预期， 对歧视没有任何影响， 主观效果的显著变化很少。另一方面，在一项研究中， 当参与者被要求命名（标签）他们认为 他们的回答反映了 实验这项研究对药物歧视有启示 方法学和影响人类吸毒的因素。

The section is studying the clinical pharmacology of drug of abuse and potential treatment medications as part of our program to evaluate new treatments. Potential treatment medications are tested for abuse potential and screened for interactions with drug of abuse that might have efficacy and/or safety implications. The first phase of a study evaluating the safety and abuse potential of buprenorphine, a partial opioid agonist under development for treatment of opioid dependence, has been completed. Although the safety of SL buprenorphine in experienced opioid users without physical dependence has been reported at doses up to 32 mg, concerns have been raised about the potential acute health risk of buprenorphine if diverted and used by the IV route at doses equivalent to those used for maintenance. Buprenorphine was tested in a single-blind, double-dummy design in doses up to 16 mg IV and 12 mg SL. Vital signs and oxygen saturation and subjective and behavioral effects were monitored for up to 72 hours. There were no significant changes in oxygen saturation and only mild effects on blood pressure. Buprenorphine produced increases in positive subjective measures compared to placebo, but these effects did not increase in an orderly dose-related manner. The results are consistent with a ceiling effect and partial agonist activity. The abuse potential of IV buprenorphine does not appear to increase with dose, nor does there appear to be a substantial difference in abuse potential between IV and SL buprenorphine at the doses tested. Buprenorphine also appears to have a ceiling for cardio-respiratory effects and a high safety margin when administered by the IV route in the absence of other drugs. Other studies in the section have examined the influence of instructions and expectations on the reactions of humans to psychoactive drugs. Instructions and expectations have been shown to influence consumption levels, the ability of a drug to function as a reinforcer, its subjective effects, as well as other physiological effects. To further examine the influence of instructions of drug response, recreational drug users were trained to discriminate between 75 mg tripelennamine and placebo in two experiments differing in instructional set in a standard drug discrimination paradigm. Participants were instructed that one of the two drugs was more sedative-like than the other drug and during the other experiment one of the two drugs was more stimulant-like. Discrimination of diazepam and amphetamine was then tested in each experiment. The results indicated that instructions designed to give participants expectations as to the types of drugs they would be administered produced no effect on discrimination and only a few significant changes in subjective effects. On the other hand, when participants were asked to name (label) the drug they believed they received, their answers reflected the instructional set of the experiment. The study has implications for drug discrimination methology and for the factors that influence drug taking in humans.