Cannabis Toxicology in Relation to Neurocognitive Outcomes in Adolescents

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PROJECT SUMMARY/ABSTRACT. While significant changes in cannabis potency, methods of use (e.g., flower, edibles) and policy have occurred, high levels of use by youth remain relatively constant. In addition, rates of secondhand cannabis exposure in children is increasing. The cannabis plant contains over 120 cannabinoid constituents, with delta-9-tetrahydrocannabinol (THC), a psychoactive constituent, most associated with deficits in verbal memory, attention, and working memory; however, the persistence of these effects remains controvertible. Differences in frequency, method of use, and potency may produce variation in measures of cannabis metabolized. Research to-date has primarily relied on self-report, despite potential mis- reporting by participants and reliance on episodic (rather than dose or patterns) of cannabis use, and almost no research investigating secondhand exposure. Such limitations may explain prior inconsistencies in the cannabis-cognition literature. The primary aim of this K08 proposal is to facilitate interdisciplinary expertise in toxicology to examine cannabinoid analyte levels using a robust biosample (hair) to assess cognitive correlates. The use of hair allows for improved methodological investigation of the relationship between cannabis use, secondhand smoke exposure, and potential cognitive impact. Expansion of hair analysis in the Adolescent Brain Cognitive Development (ABCD) study will add novel and important knowledge to the scientific body of literature regarding the cannabis-cognition link, clarifying prior discrepant results of both negative and null cognitive function changes associated with cannabis using adolescents, and examining the influence of second-hand cannabis smoke. Causal inference models will be used to determine the influence of THC and its metabolite levels from hair on cross-sectional and longitudinal cognitive function among a subsample of the ABCD cohort. Cognition and substance use will be measured annually for the length of the proposed project, when ABCD participants are between the ages of 13-14 and 17-18 years. The aims of this project are consistent with NIDA's strategic funding plans, as this work would measure behavioral sequelae of environmental and direct exposure of cannabis in a vulnerable, young population. The additional training afforded to Dr. Wade, particularly in cannabis toxicology, secondhand smoke exposure, early adolescence, and statistics, would complement her prior experience in substance use, neurocognition, and emerging adults. A mentorship team of experts will bridge these unique fields to improve our understanding of the effects of THC exposure (personal use or environmental exposure) on adolescent cognitive development. At the conclusion of this award, Dr. Wade will meet her goal of career independence as an interdisciplinary clinical scientist with expertise in cannabis toxicology and cognition, exemplified by submission of an R01. Finally, the funding of analysis of additional hair samples will also benefit the open-science model of ABCD, as all data collected will be available to researchers worldwide through the annual curated ABCD data release.