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.
This proposal focuses on the effects of heavy cannabis use during adolescence on brain morphology and cognitive performance in an aging population. We will use high-resolution magnetic resonance imaging, white matter metrics, and neuropsychological testing to investigate gray matter, white matter and cognition in heavy cannabis users, and non-users. Additionally, we will investigate whether morphological brain differences are synergistically related to APOE ?4, the variant that increases risk for late life cognitive decline.
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