Characterization of the Response to the Kappa Opiate Agonist Salvinorin A in Heal

描述(申请人提供)：健康人对kappa阿片激动剂salvinorin A的反应特征背景：salvinorin A(SA)是从致幻植物丹参的叶子中提取的活性化合物，在墨西哥传统仪式中已使用了几个世纪。最近，SA的致幻作用在娱乐上的使用在年轻人中越来越受欢迎。然而，目前还没有关于SA对人类影响的受控数据。SA的独特之处在于它是一种仅在kappa阿片受体(KOR)上具有高度选择性的激动剂，并可能通过在该受体上的激动剂来产生其拟精神分裂效应。虽然人们越来越多地认识和关注SA的娱乐性使用，但还没有系统地描述其对人类影响的对照研究。目的：研究吸入SA对健康人体的行为、主观、强化、认知、生理、神经内分泌和心理生理等方面的剂量相关效应。研究设计与方法：从社区招募33名健康受试者，征得同意后仔细筛选参与。受试者将在3个不同的测试日以双盲方式接受安慰剂或两种有效SA剂量(20,005克或30,005克)中的一种。每个测试日将收集行为、主观、认知和生理数据。闭眼吸气3分钟后立即进行静息脑电检查。行为测量将包括临床医生用药分离症状量表、精神分裂状态问卷、迷幻剂评定量表和阳性和阴性症状量表。主观效果将在视觉模拟标尺(VAS)上进行测量。认知测量将包括向前数字、向后数字和字母数字排序任务。将测量生理参数(血压、脉率、脉搏血氧饱和度)和瞳孔大小。将经常采集血液样本，以分析SA和血浆催乳素水平。影响/意义：在过去几年中，萨尔维诺林A的娱乐性使用率一直在迅速增加，尽管没有受到联邦政府的控制，但越来越多的州已经通过立法控制其使用。然而，关于SA对人类产生的影响的公开数据非常有限。因此，人们对SA使用的日益关注，加上该领域研究的匮乏，迫切需要从公共卫生和监管的角度系统地表征其在人类中与剂量相关的主观、行为、认知和生理影响。

DESCRIPTION (provided by applicant): Characterization of the response to kappa opiate agonist Salvinorin A in healthy humans Background: Salvinorin A (SA) is the active compound derived from the leaves of the hallucinogenic plant Salvia divinorum, which has been used for centuries in traditional Mexican rituals. More recently, the recreational use of SA for its hallucinogenic effects is increasingly popular amongst young adults. However, there are no controlled data on the effects of SA in humans. SA is unique in being a highly selective agonist solely at the kappa opioid receptor (KOR) and presumably produces its psychotomimetic effects by agonism at this receptor. While there is increasing recognition and concern about the recreational use of SA, there are no controlled studies systematically characterizing its effects in humans. Aims: To characterize the dose-related behavioral, subjective, reinforcing, cognitive, physiological, neuroendocrine and psycho-physiological effects of inhaled SA in healthy humans. Research Design and Methods: 33 healthy subjects will be recruited from the community and after obtaining consent will be carefully screened for participation. Subjects will receive, on 3 separate test days, either placebo or one of two active SA doses (20,005g or 30,005g) through an inhaled route, in a double blind manner. Behavioral, subjective, cognitive and physiological data will be collected throughout each test day. Resting EEG will be obtained immediately after inhalation for 3 minutes with eyes closed. Behavioral measures will include the Clinician Administered Dissociative Symptoms Scale, the Psychotomimetic States Inventory, the Hallucinogen Rating Scale, and the Positive and Negative Syndrome Scale. Subjective effects will be measured on a Visual Analog Scale (VAS). Cognitive measures will include digits forward, digits backward and the letter number sequencing task. Physiological parameters (blood pressure, pulse rate, pulse oximetry) and pupil size will be measured. Blood will be sampled frequently for analysis of SA and plasma prolactin levels. Impact/Significance: The rates of recreational use of Salvinorin A have been rapidly increasing over the last few years and although not federally controlled, a growing number of states have passed legislation controlling its use. However, there is very limited published data on the effects induced by SA in humans. Thus, the growing concern about SA use coupled with the paucity of research in this area presents an urgent need to systematically characterize its dose related subjective, behavioral, cognitive and physiological effects in humans both from a public health as well as regulatory perspective.