Effects of heavy adolescent cannabis use on brain morphology in aging

大麻（Cannabis sativa）是全球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，460万人符合依赖标准，强调了了解使用的生物学影响的公共卫生重要性。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的发展电路，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，许多在青少年时期大量使用大麻的人现在进入了老年，与年龄相关的认知能力下降可能开始。在20世纪70年代，大麻的使用在不到十年的时间里翻了一番，当时美国药物滥用调查中有38%的受访者报告使用大麻，其中12%的用户报告每月使用大麻超过20次。了解早期使用大麻如何影响神经生物学和认知结果对于这个老龄化人口非常重要，因为他们已经面临衰老中记忆和认知缺陷的风险。由于大麻的使用似乎对海马体有主要影响，海马体是记忆的主要结构，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过程中最大。据我们所知，没有研究调查青少年使用大麻对老龄化人群海马形态和认知能力的长期影响。 我们将使用高分辨率磁共振成像（MRI），扩散张量成像（DTI）和神经心理学测试研究海马的完整性和认知能力，这些测试是在青春期每月使用大麻超过20次至少一年的老年人群（55 - 70岁）中进行的。在我们建议入组该重度使用类别的30例受试者中，我们已经确定了9例受试者，并收集了这些受试者的MRI、DTI和认知测试数据。我们将从重度大麻使用者收集的数据与未使用大麻但年龄，性别，教育，轻度烟草和轻度酒精使用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海马形态和衰老中的记忆衰退，我们将调查重度大麻使用者中APOE 4变体的拥有是否与海马皮质变薄和白质缺陷协同相关。 该项目通过建立她以前在衰老大脑神经成像方面的研究优势，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。该培训计划结合了正式的课程，一对一的指导与博士Edythe伦敦，在成瘾研究的既定调查员，以及一系列的会议和研讨会，以促进候选人在成瘾研究的增长。

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.