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（如积极的情绪表达）和社会威胁（如愤怒或恐惧的表达）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，尽管吸毒的动机与社会环境密切相关，但对于滥用毒品是否会影响社会处理，无论是短期的还是长期的，我们知之甚少。有趣的是，许多吸毒者报告说，药物增强了社交体验，使互动更容易或更愉快；这些所谓的影响似乎激发了一些药物的使用。因此，社会处理的急剧变化可能构成某些（如果不是全部的话）滥用药物的强化作用的一个方面。如果这是真的，这种新机制可能有助于开始和/或维持药物使用，以及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处理的影响。因此，目前仍不清楚吸毒者关于增强药物社会效应的信念是基于误解还是基于事实。这项初步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，收集了两种滥用药物——13,4-亚甲基二氧甲基苯丙胺（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的初步数据。健康的男性和女性志愿者（N=16），有娱乐性的摇头丸和大麻暴露，在完成基于实验室的社会处理测量之前，他们将接受3个疗程的口服MDMA (1.5 mg/kg), THC （10 mg）或安慰剂。措施将包括药理学功能磁共振成像（phMRI）协议中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，重点关注社交能力和社交不适。我们假设MDMA会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。我们假设四氢大麻酚会降低社会威胁反应和社会不适；但对对积极的社会材料的反应没有影响。根据I/START的目标，获得的试点数据将用于开展更大规模的（R01）成像调查，研究一系列药物和剂量对社会处理的影响。项目成果将有助于科学理解一种尚未得到充分研究的急性药物效应，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)个体对某些药物的偏好；3)开始和/或维持药物使用。因此，这个项目将开始全面评估药物对社会处理的严重影响，有可能产生重大影响。

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.