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

背景：Salvinorin A （SA）是从致幻植物鼠尾草（Salvia divinorum）的叶子中提取的活性化合物，在墨西哥传统仪式中使用了几个世纪。最近，SA的致幻剂的娱乐性使用在年轻人中越来越流行。然而，还没有关于SA对人类影响的对照数据。SA是一种独特的高度选择性激动剂，仅在kappa阿片受体（KOR）上，可能通过对该受体的激动作用产生拟精神作用。虽然人们对SA的娱乐性使用的认识和关注越来越多，但还没有系统地描述其对人类影响的对照研究。目的：探讨健康人体吸入SA的剂量相关行为、主观、强化、认知、生理、神经内分泌和心理生理效应。研究设计与方法：从社区招募33名健康受试者，征得同意后进行仔细筛选。受试者将在3个独立的测试日以双盲方式，通过吸入途径接受安慰剂或两种活性SA剂量（20005g或30005g）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分钟后立即静息脑电图。行为测量将包括临床医生管理的分离症状量表、拟精神状态量表、致幻剂评定量表和阳性和阴性综合征量表。主观效果将在视觉模拟量表（VAS）上进行测量。认知测试将包括数字向前，数字向后和字母数字排序任务。将测量生理参数（血压、脉搏率、脉搏血氧仪）和瞳孔大小。经常抽血分析SA和血浆催乳素水平。影响/意义：在过去几年中，娱乐性使用Salvinorin A的比率迅速增加，尽管没有联邦管制，但越来越多的州已经通过立法控制其使用。然而，关于SA对人类的影响，发表的数据非常有限。因此，对SA使用的日益关注，加上这一领域研究的缺乏，迫切需要从公共卫生和监管的角度系统地描述其剂量对人类的主观、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.