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

• 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
• 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' 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

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（大麻）是全世界使用最广泛的非法药物，2010年有1740万美国人报告上个月使用大麻，460万人符合依赖标准，这强调了了解使用的生物学影响对公共卫生的重要性。大量使用大麻如何影响晚年的大脑结构和认知能力尚不清楚。青少年大脑的持续成熟，包括记忆表现和执行控制背后的发育回路，使青少年大脑处于大量使用大麻的有害影响的高风险之中。随着“婴儿潮”一代的老龄化，许多青少年时期大量吸食大麻的人现在进入老年，与年龄相关的认知能力下降可能开始。在20世纪70年代，大麻的使用量在不到十年的时间里翻了一番，当时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。了解早期大量使用大麻对神经生物学和认知结果的影响对老龄化人口来说非常重要，因为他们已经面临着衰老导致记忆和认知缺陷的风险。由于大麻使用似乎主要影响海马，海马是记忆的主要结构，也是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，我们预计慢性大麻使用的影响可能在衰老期间最大。据我们所知，没有研究调查了青少年大麻使用对老年人群海马形态和认知表现的长期影响。我们将使用高分辨率磁共振成像（MRI）、弥散张量成像（DTI）和神经心理测试来研究海马完整性和认知表现，研究对象是年龄在55-70岁之间的老年人，他们在青少年时期每月使用大麻超过20次，持续至少一年。在我们拟纳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。我们将把从重度大麻使用者收集的数据与不使用大麻但在年龄、性别、教育程度、轻度烟草和轻度酒精使用方面相匹配的受试者进行比较。最后，由于已知家族史和遗传风险会加速衰老过程中的海马形态和记忆衰退，我们将研究重度大麻使用者携带APOE¿4变异是否与海马皮质变薄和白质缺陷有协同关系。该项目通过建立候选人之前在衰老大脑神经成像方面的研究优势，同时在成瘾研究方面提供新的培训和指导，从而推进候选人的培训。培训计划结合了正式的课程，与Edythe London博士进行一对一的指导，Edythe London博士是一位知名的成瘾研究研究者，以及一系列的会议和研讨会，以促进候选人在成瘾研究方面的成长。