Marijuana Use and Schizophrenia

大麻使用和精神分裂症

• 批准号: 8144919
• 负责人: Daniel S. O Leary
• 金额: $ 17.8万
• 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 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8144919
• 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，该项目旨在调查精神分裂症患者和健康志愿者之间在大麻对大脑和行为的影响方面的差异。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吸食大麻与精神分裂症发病率较高有关。还有证据表明，大量吸食大麻可能会诱发急性精神病，也有证据表明，长期吸食大麻可能会导致易感人群出现精神分裂症。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大脑结构和功能的复杂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丰富的专业知识。我们在评估急性大麻使用对非精神分裂症大麻使用者的局部脑血流 (rCBF) 和认知的影响方面也拥有丰富的经验。该 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 名精神分裂症受试者和 10 名经常吸食大麻的匹配正常志愿者的 PET 和 MR 成像数据以及临床症状评级。使用[15O]水进行 PET 成像将用于在货币奖励协议期间测量 rCBF 数据。受试者将在吸食安慰剂香烟之前和之后以及吸食活性大麻香烟之前和之后使用 PET 和 [15O] 水进行一次扫描。在 PET 成像过程中，受试者将执行一项金钱奖励任务，其他研究发现该任务可以激活与奖励相关的大脑区域。 PET 图像将与高分辨率结构 MRI 扫描共同配准以进行分析。受试者还将在单独的场合用神经心理学电池进行评估。精神分裂症受试者将根据年龄、性别、父母社会经济地位和吸烟史与正常志愿者受试者进行匹配。我们假设吸食大麻对精神分裂症患者 rCBF 的影响将与我们正常志愿者中观察到的显着不同。更具体地说，我们假设精神分裂症受试者的大脑奖励系统中的 rCBF 在基线时（即吸食安慰剂后）较低，但在吸食大麻后会表现出正常的奖励激活模式。 公共卫生相关性：越来越多的证据表明吸食大麻与精神分裂症之间存在联系，并且有证据表明精神分裂症患者的大脑奖励系统可能存在异常。这项研究将在奖励任务中使用 PET 成像来比较精神分裂症患者和经常吸食大麻的健康志愿者在吸食安慰剂或活性大麻香烟后大脑中的血流变化。该研究结果将进一步加深我们对精神分裂症根本原因的理解，并可能为治疗这种疾病提供新的可能性。