Marijuana Use and Schizophrenia

描述（由申请人提供）：这是一个旨在调查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的项目的最后一次重新提交。总体目标是确定精神分裂症是否会增加大麻使用的认知和临床影响。有流行病学证据表明大麻的使用与精神分裂症的高发病率有关。也有证据表明，重度吸食大麻会诱发急性精神病，同时也有证据表明，长期吸食大麻会导致易感人群患上精神分裂症。此外，已发现注射四氢大麻酚会导致健康志愿者的精神分裂症样症状增加，并会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标以及复杂的大脑结构和功能测量来评估精神分裂症患者和正常志愿者之间的差异方面拥有广泛的专业知识。我们在评估急性大麻使用对非精神分裂症大麻使用者的区域脑血流量（rCBF）和认知的影响方面也有经验。本R21申请提出了一项将这两个研究项目联系起来的研究。我们建议获取10名精神分裂症患者和10名经常吸食大麻的正常志愿者的PET和MR成像数据和临床症状评分。在货币奖励方案中，将使用[15O]水的PET成像来测量rCBF数据。受试者将在抽安慰剂香烟前后，以及抽活性大麻香烟前后，分别用[15O]水进行一次PET扫描。在PET成像过程中，受试者将执行一项金钱奖励任务，这项任务在其他研究中被发现会激活与奖励相关的大脑区域。PET图像将与高分辨率结构MRI扫描共同注册以进行分析。受试者还将在单独的场合接受神经心理学测试。精神分裂症受试者将根据年龄、性别、父母的社会经济地位和吸烟史与正常志愿者受试者相匹配。我们假设，吸食大麻对精神分裂症患者rCBF的影响将与我们在正常志愿者中看到的显著不同。更具体地说，我们假设精神分裂症受试者的rCBF在基线时（即吸烟安慰剂后）的大脑奖励系统较低，但在吸食大麻后会显示出正常的奖励激活模式。

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.