Effects of Heavy Adolescent Cannabis Use on Brain Morphology in Aging

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.

Investigators 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. Investigators 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, the investigators will investigate whether possession of the APOE ε4 variant in heavy cannabis users is synergistically related to thinner hippocampal cortex and white matter deficits.