Effects of heavy adolescent cannabis use on brain morphology in aging

青少年大量使用大麻对衰老过程中大脑形态的影响

基本信息

批准号：
8985674
负责人：
ALISON CLEMENTS BURGGREN
金额：
$ 15.53万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-01-01 至 2017-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8985674
关键词：
Address Adolescence Adolescent Affect Age Age-associated memory impairment Aging Alcohol consumption Alzheimer&apos s Disease American Animals Anisotropy Area Biological Brain Brain imaging Brain region Cannabis Cannabis sativa plant Categories Chronic Cognition Cognitive Cognitive deficits Data Delayed Memory Dementia Dependence Development Diffusion Magnetic Resonance Imaging Dose Drug abuse Education Educational workshop Elderly Enrollment Family Fostering Frequencies Gender Generations Genes Genetic Genetic Risk Genetic Status Genotype Growth Health Hippocampus (Brain)Impaired cognition Length Life Light London Long-Term Effects Magnetic Resonance Imaging Marijuana Measures Memory Memory Loss Memory impairment Mentors Mentorship Morphology Neurobiology Neuropsychological Tests Outcome Performance Persons Predisposition Prefrontal Cortex Public Health Qualifying Recording of previous events Regression Analysis Reporting Research Research Personnel Resolution Risk Series Smoking Source Structure Surveys Tetrahydrocannabinol Thick Time Tobacco Training Training Programs Translating Variant Width addiction age related aging brain aging population base brain morphology cannabinoid receptor cognitive performance cognitive testing executive function gray matter high risk illicit drug use marijuana use marijuana user meetings memory encoding neuroimaging neurotoxic pre-clinical risk variant white matter

项目摘要

DESCRIPTION (provided by applicant): Marijuana (Cannabis sativa) is the most widely used illicit drug worldwide, with 17.4 million Americans reporting past month use in 2010 and 4.6 million meeting criteria for dependence, underscoring the public health importance of understanding the biological implications of use. How heavy cannabis use affects brain structure and cognitive performance in late life is unknown. The ongoing maturation in the adolescent brain, including the developmental circuitry underlying memory performance and executive control puts the adolescent brain at high risk for detrimental effects of heavy cannabis use. With the aging of the 'baby boomer' generation, many people who used cannabis heavily as adolescents are now entering their senior years when age-related cognitive decline may begin. Cannabis use doubled in less than a decade during the 1970's when 38% of those surveyed in the U.S. Survey on Drug Abuse reported using cannabis and 12% of those users reported using cannabis more than 20 times a month. Understanding how heavy, early cannabis use may affect neurobiological and cognitive outcomes is of high importance for this aging population, which is already at risk for memory and cognitive deficits in aging. Because cannabis use appears to have a primary effect within the hippocampus, the main structure for memory and the structure affected most by age-related memory impairments and pre-clinical Alzheimer's disease, we expect that the effects of chronic cannabis use may be greatest during aging. To our knowledge, no study has investigated the long-term effects of adolescent cannabis use on hippocampal morphology and cognitive performance in an aging population. We will investigate hippocampal integrity and cognitive performance using high-resolution magnetic resonance imaging (MRI), diffusion tensor imaging (DTI) and neuropsychological testing in an aging population of subjects (55-70 years old) who used cannabis more than 20 times a month for at least a year during adolescence. Of the 30 subjects we propose to enroll in this heavy use category, we have already identified 9 subjects, and collected MRI, DTI and cognitive testing data for these subjects. We will compare data collected from heavy cannabis users to subjects who did not use cannabis but are matched for age, gender, education, light tobacco and light alcohol use. Finally, because family history and genetic risk are known to accelerate hippocampal morphology and memory decline in aging, we will investigate whether possession of the APOE ¿4 variant in heavy cannabis users is synergistically related to thinner hippocampal cortex and white matter deficits. This project advances the Candidate's training by building on the strengths of her previous research in neuroimaging of the aging brain while providing new training and mentorship in addiction research. The training program combines formal coursework, one-on-one mentoring with Dr. Edythe London, an established investigator in addiction research, and a series of meeting and workshops to foster the Candidate's growth in addiction research.

描述（由申请人提供）：大麻 (Cannabis sativa) 是全世界使用最广泛的非法药物，2010 年有 1,740 万美国人报告上个月使用过大麻，其中 460 万美国人达到依赖标准，这强调了了解大麻的生物学影响对公共卫生的重要性。大量使用大麻对晚年大脑结构和认知表现的影响尚不清楚，青少年大脑的持续成熟，包括记忆表现和执行控制的发育回路。青少年大脑因大量使用大麻而出现疼痛的风险很高。随着“婴儿潮一代”的老龄化，许多在青少年时期大量使用大麻的人现在正进入老年，与年龄相关的认知能力可能会开始下降。在 1970 年代不到十年的时间内翻了一番，美国药物滥用调查中 38% 的受访者报告使用大麻，其中 12% 的使用者报告每月使用大麻超过 20 次。早期使用大麻可能会影响神经生物学和认知结果，这对于老年人群来说非常重要，因为大麻的使用似乎对海马体（记忆和认知的主要结构）产生主要影响，因此老年人已经面临着记忆和认知缺陷的风险。由于受年龄相关记忆障碍和临床前阿尔茨海默病影响最大的结构，我们预计长期使用大麻的影响可能在衰老过程中最大，据我们所知，没有研究调查青少年使用大麻对身体的长期影响。海马形态和认知我们将使用高分辨率磁共振成像 (MRI)、扩散张量成像 (DTI) 和神经心理学测试来研究使用大麻的老年人群（55-70 岁）的海马完整性和认知表现。在青春期期间至少一年内每月超过 20 次，在我们建议加入这一重度使用类别的 30 名受试者中，我们已经确定了 9 名受试者，并收集了这些受试者的 MRI、DTI 和认知测试数据。将比较从大量大麻使用者和不使用大麻但年龄、性别、教育程度、轻度吸烟和轻度饮酒的受试者中收集的数据，因为已知家族史和遗传风险会加速海马形态和记忆力的下降。老化时，我们会调查是否拥有APOE ¿重度大麻使用者的 4 变异与海马皮层变薄和白质缺陷具有协同作用，该项目通过利用她之前在衰老大脑神经影像学方面的研究优势，同时提供成瘾研究方面的新培训和指导，来推进候选人的培训。该项目结合了正式的课程作业、与成瘾研究领域知名研究者 Edythe London 博士的一对一指导，以及一系列会议和研讨会，以促进候选人在成瘾研究方面的发展。