Marijuana Use and Schizophrenia

大麻使用和精神分裂症

• 批准号: 7989463
• 负责人: Daniel S. O Leary
• 金额: $ 20.96万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7989463
• 关键词: Acute; Age; Aphasia; Area; Blood flow; Brain; Brain region; Cannabis; Cerebellum; Cerebrovascular Circulation; Cigarette; Clinical; Clinical Data; Cognition; Cognitive; Corpus striatum structure; Data; Delusions; Disease; Epidemiology; Gender; Hallucinations; Impaired cognition; Incidence; Individual; Injection of therapeutic agent; Lead; Link; Location; MRI Scans; Magnetic Resonance Imaging; Marijuana; Marijuana Smoking; Measures; Mediating; Moods; Patients; Pattern; Performance; Placebos; Positron-Emission Tomography; Protocols documentation; Psychotic Disorders; Publishing; Recording of previous events; Reporting; Research; Resolution; Rewards; Scanning; Schizophrenia; Smoke; Smoking; Smoking History; Structure; Substance abuse problem; Symptoms; System; Testing; Water; base; blind; brain behavior; cannabinoid receptor; clinical effect; design; experience; frontal lobe; healthy volunteer; indexing; marijuana user; neuropsychological; programs; public health relevance; response; reward processing; volunteer

DESCRIPTION (provided by applicant): This is the final resubmission of a project designed to investigate differences between schizophrenic individuals and healthy volunteers in the effects of marijuana on the brain and behavior. The overall aim is to determine whether schizophrenia confers an increased liability to the cognitive and clinical effects of cannabis use. There is epidemiological evidence linking marijuana use with a higher incidence of schizophrenia. There is also evidence that acute psychosis can be induced by heavy marijuana use, as well as evidence that prolonged marijuana use can lead to the onset of schizophrenia in susceptible individuals. Additionally, injection of THC has been found to cause increased schizophrenia-like symptoms in healthy volunteers and to increase symptoms in patients with schizophrenia. Our research team has extensive expertise in assessing differences between schizophrenics and normal volunteers using cognitive and clinical indices, as well as sophisticated measures of brain structure and function. We are also experienced in assessing the effects of acute marijuana use on regional cerebral blood flow (rCBF) and cognition in non-schizophrenic users of marijuana. This R21 application proposes a study that links these two research programs. We propose acquiring PET and MR imaging data and clinical symptom ratings on 10 schizophrenic subjects and 10 matched normal volunteers who are regular users of marijuana. PET imaging with [15O]water will be used to measure rCBF data during a monetary reward protocol. Subjects will be scanned using PET with [15O]water on one occasion, before and after smoking a placebo cigarette, and before and after smoking an active marijuana cigarette. During PET imaging the subjects will perform a monetary reward task that was found to activate reward-related brain regions in other studies. The PET images will be co-registered to a high resolution structural MRI scan for analysis. The subjects will also be assessed on a separate occasion with a neuropsychological battery. The schizophrenic subjects will be matched by age, gender, parental SES, and smoking history to the normal volunteer subjects. We hypothesize that the effects of smoking marijuana on rCBF in schizophrenics will differ significantly from that seen in our normal volunteers. More specifically, we hypothesize that rCBF will be lower in brain reward systems in schizophrenic subjects at baseline (i.e., after smoking placebo), but will show a normal pattern of activation to reward after smoking marijuana. PUBLIC HEALTH RELEVANCE: There is increasing evidence that there is a link between marijuana use and schizophrenia, as well as evidence that schizophrenic individuals may have abnormalities in their brain reward systems. This study will use PET imaging during a reward task to compare blood flow changes in the brains of schizophrenics and healthy volunteers who regularly use marijuana after they smoke either a placebo or an active marijuana cigarette. Results of the study will further our understanding of the underlying causes of schizophrenia and could suggest new possibilities for treatment of this disorder.

描述（由申请人提供）：这是一个项目的最终重新提交，该项目旨在研究精神分裂症患者和健康志愿者在大麻对大脑和行为的影响方面的差异。总体目的是确定精神分裂症是否承担对大麻使用的认知和临床影响的责任。有流行病学的证据将大麻使用与精神分裂症的发病率更高。也有证据表明，大麻使用大麻可以引起急性精神病，并证明长时间使用大麻可以导致易感人群的精神分裂症发作。此外，已经发现注射THC会导致健康志愿者的精神分裂症样症状增加，并增加精神分裂症患者的症状。我们的研究团队在使用认知和临床指数以及对大脑结构和功能的复杂衡量标准评估精神分裂症和正常志愿者之间的差异方面具有广泛的专业知识。我们还经验丰富，可以评估急性大麻对大麻非静态使用者对脑血流（RCBF）和认知的影响。该R21应用程序提出了一项将这两个研究计划联系起来的研究。我们建议对10名精神分裂症受试者以及10名匹配的正常志愿者获得PET和MR成像数据和临床症状等级，这些志愿者是大麻的常规使用者。在货币奖励方案中，使用[15o]水的PET成像用于测量RCBF数据。在抽烟之前和之后，将使用宠物和[15o]水的宠物扫描受试者，并在吸烟之前和之后抽大麻。在PET成像期间，受试者将执行一项货币奖励任务，该任务被发现在其他研究中激活与奖励相关的大脑区域。 PET图像将被共同注册到高分辨率的结构MRI扫描以进行分析。这些受试者还将在神经心理电池的不同场合进行评估。精神分裂症受试者将以年龄，性别，父母SES和吸烟史与正常的志愿者受试者相匹配。我们假设吸烟大麻对精神分裂症患者RCBF的影响与我们正常志愿者中的影响有很大差异。更具体地说，我们假设RCBF在基线时（即吸烟安慰剂后）的精神分裂症受试者的大脑奖励系统中的RCBF将较低，但在吸烟大麻后将显示出正常的激活模式以奖励。 公共卫生相关性：越来越多的证据表明大麻使用与精神分裂症之间存在联系，以及精神分裂症患者可能在其大脑奖励系统中有异常的证据。这项研究将在奖励任务期间使用PET成像，以比较精神分裂症患者大脑的血流变化和健康的志愿者，他们在吸烟或活跃的大麻香烟后会定期使用大麻。该研究的结果将进一步了解精神分裂症的根本原因，并可能提出治疗这种疾病的新可能性。