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

描述（由申请人提供）：健康人对κ阿片激动剂鼠尾草素A的反应的表征背景：鼠尾草素A（SA）是衍生自致幻植物鼠尾草（Salvia divinorum）的叶的活性化合物，其已在传统墨西哥仪式中使用了几个世纪。最近，SA的致幻作用在年轻人中越来越受欢迎。然而，没有关于SA对人体影响的对照数据。SA的独特之处在于其仅在κ阿片受体（KOR）上是高度选择性激动剂，并且推测其通过激动该受体而产生拟精神病作用。虽然人们越来越认识到和关注SA的娱乐用途，但没有系统地描述其对人类影响的对照研究。目的：描述吸入SA对健康人的剂量相关行为、主观、强化、认知、生理、神经内分泌和心理生理效应。研究设计和方法：将从社区招募33名健康受试者，在获得知情同意后，将仔细筛选是否参与研究。受试者将在3个单独的试验日以双盲方式通过吸入途径接受安慰剂或两种活性SA剂量之一（20，005 g或30，005 g）。将在每个测试日收集行为、主观、认知和生理数据。在闭眼吸入3分钟后立即获取静息EEG。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。将采用视觉模拟量表（VAS）测量主观效应。认知测量将包括数字向前，数字向后和字母数字排序任务。将测量生理参数（血压、脉率、脉搏血氧饱和度）和瞳孔大小。将经常采集血液样本，用于分析SA和血浆催乳素水平。影响/意义：在过去几年中，Salvinorin A的娱乐使用率迅速增加，尽管不受联邦政府控制，但越来越多的州已经通过立法控制其使用。然而，关于SA在人体中诱导的影响的已发表数据非常有限。因此，越来越多的关注SA的使用加上在这一领域的研究的缺乏，提出了一个迫切需要系统地表征其剂量相关的主观，行为，认知和生理影响在人类从公共卫生以及监管的角度。 公共卫生相关性：越来越多的人关注致幻药物Salvinorin A（SA）的娱乐用途，该药物在年轻人中迅速流行。关于SA在人体中引起的范围效应的文献极其有限，主要由SA使用者的轶事报告组成。因此，由于缺乏这方面的数据，迫切需要系统地表征该药物在人体中的广泛剂量相关效应。

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. PUBLIC HEALTH RELEVANCE: There is increasing concern about the recreational use of the hallucinogenic drug Salvinorin A (SA) that is rapidly gaining popularity amongst young adults. The literature on the range effects induced by SA in humans is extremely limited and consists mainly of anecdotal reports from SA users. The lack of data in this area thus presents a compelling need to systematically characterize a wide range of dose related effects of this drug in humans.