Effects of MDMA ("ecstasy") and THC on Social Processing

描述（由申请人提供）：社会信息的处理，如社会奖励（例如，积极的情绪表达）和社会威胁（例如，愤怒或恐惧的表情）刺激，在一系列原发性精神障碍中发生改变。这种改变越来越被认为是精神病理学的重要功能组成部分。然而，尽管使用药物的动机与社会背景密切相关，但人们对药物滥用是否会严重或长期影响社会处理知之甚少。有趣的是，许多使用者报告说，药物增强了社会体验，使互动更容易或更愉快;这些所谓的效果似乎激发了一些药物的使用。因此，社会过程的急剧变化可能构成某些（如果不是全部）滥用药物的强化效应的一个方面。如果这是真的，这种新的机制可能有助于启动和/或维持药物使用和个人对某些药物的偏好。很少有对照研究调查药物对人类社会过程的影响。因此，在很大程度上仍然不清楚吸毒者关于毒品对社会的促进作用的信念是基于误解还是事实。这项试点研究采用了功能成像，急性药物管理和社会神经科学任务的强大组合，以收集初步数据，表征两种滥用药物，13，4-亚甲二氧基甲基苯丙胺（MDMA;“摇头丸”）和D9四氢大麻酚（THC，大麻的主要精神活性成分）对人类社会奖励和社会威胁处理的影响。健康的男性和女性志愿者（N=16），娱乐性摇头丸和大麻暴露，将经历3个会议，其中他们将被管理口服MDMA（1.5毫克/公斤），THC（10毫克），或安慰剂，在完成实验室为基础的社会处理措施。措施将包括在药理学功能磁共振成像（phMRI）协议中的社会奖励和社会威胁的标准化探针，以评估药物对社会食欲和厌恶物质的神经和行为处理的影响。我们还将测量主观药物效应，重点是社交能力和社交不适。我们假设MDMA将1）增加社会奖励反应和主观社交性; 2）减少社会威胁反应和社会不适。我们假设THC将1）减少社会威胁反应和社会不适;但将2）对积极的社会材料的反应没有影响。根据I/START的目标，获得的试验数据将用于启动一系列药物和剂量对社会处理影响的更大（R 01）成像调查。项目结果将有助于科学地理解研究不足的急性药物效应，这种效应可能影响：1）在药物影响下的人际行为，包括危险行为; 2）个人对某些药物的偏好; 3）开始和/或维持药物使用。因此，这一项目将全面评估药物对社会进程的急性影响，有可能产生重大影响。 公共卫生相关性：尽管一些吸毒者报告说，他们使用毒品使社会交往更容易和更愉快，但人们对毒品对社会经验的影响知之甚少。这个试点项目使用一种新颖的，多维度的，基于成像的方法来研究两种在社会环境中常用的药物，MDMA（“摇头丸”）和THC（在大麻中发现）对人类社会信息处理的影响。我们预计，研究结果将提高对吸毒社会动机的科学认识，最终有助于更好地预防和治疗吸毒。

DESCRIPTION (provided by applicant): Processing of social information, such as socially rewarding (e.g., positive emotional expressions) and socially threatening (e.g., angry or fearful expressions) stimuli, is altered in a range of primary psychiatric disorders. Such alterations are increasingly recognized as important functional components of psychopathology. However, despite the fact that motivations to use drugs are closely linked with social context, little is known about whether drugs of abuse affect social processing, either acutely or longer-term. Anecdotally, many users report that drugs enhance social experiences, making interactions easier or more pleasurable; these purported effects appear to motivate some drug use. Acute alterations to social processing may, therefore, constitute an aspect of the reinforcing effects of certain, if not all, abused drugs. If this is true, this novel mechanism likely contributes to the initiation and/or maintenance of drug use and to individuals' preferences for certain drugs. Little controlled research has investigated the effects of drugs on social processing in humans. It thus remains largely unclear whether drug users' beliefs about socially enhancing drug effects are based in misperception or fact. This pilot study employs a powerful combination of functional imaging, acute drug administration and social neuroscience tasks to collect preliminary data characterizing the effects of two abused drugs, 13,4-methylenedioxymethamphetamine (MDMA; 'ecstasy') and D9tetrahydrocannabinol (THC, the primary psychoactive component of marijuana), on social reward and social threat processing in humans. Healthy male and female volunteers (N=16), with recreational ecstasy and marijuana exposure, will undergo 3 sessions in which they will be administered oral MDMA (1.5 mg/kg), THC (10 mg), or placebo, before completing laboratory-based social processing measures. Measures will include standardized probes of social reward and social threat in a pharmacological functional Magnetic Resonance Imaging (phMRI) protocol, to assess drug effects on neural and behavioral processing of socially appetitive and aversive material. We will also measure subjective drug effects, focusing on sociability and social discomfort. We hypothesize that MDMA will 1) increase social reward responses and subjective sociability; and 2) reduce social threat responses and social discomfort. We hypothesize that THC will 1) reduce social threat responses and social discomfort; but will 2) have no effect on response to positive social material. Pilot data obtained will, in keeping with I/START aims, be employed to initiate a larger (R01) imaging investigation of the effects of a range of drugs, and doses, on social processing. Project results will contribute to scientific understandings of an under-researched acute drug effect that may affect: 1) interpersonal behavior, including risky behavior, while under the influence of drugs; 2) individuals' preferences for certain drugs; and 3) initiation and/or maintenance of drug use. Thus, this project, which will initiate a comprehensive assessment of acute drug effects on social processing, has the potential for substantial impact. PUBLIC HEALTH RELEVANCE: Although some drug users report that they use drugs to make social interactions easier and more pleasurable, little is understood about the effects of drugs on social experiences. This pilot project uses a novel, multidimensional, imaging-based approach to study the effects of two drugs commonly used in social settings, MDMA ('ecstasy') and THC (found in marijuana), on social information processing in humans. We anticipate that results will improve scientific knowledge about social motivations to use drugs, ultimately contributing to better prevention and treatment for drug use.