Cannabis, Depression and Neurobiological Function in Transition-Age Youth

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Project Summary This application for a Mentored Patient-Oriented Career Development Award (K23) will allow the candidate to obtain specialized training and research expertise in new areas that will enable her to become an independent physician scientist. Dr. Fischer details a five year research plan aimed at characterizing the effects of cannabis exposure on neurobiological functioning and the evolution of depressive symptoms in transition age youth (TAY). The specific aims are to prospectively examine the impact of cannabis exposure on reward and stress system functioning, and to develop a preliminary integrative biomarker-guided model of the effects of cannabis exposure on symptoms of reward impairment and depression in TAY. Forty regular cannabis-users and 30 non-cannabis- using controls will be recruited and prospectively followed for 12 months. Participants will complete clinical and substance use assessments, perform reward and stress tests utilizing functional neuroimaging and cortisol bioassays, and provide hair samples to quantify aggregate delta-9-tetrahydrocannabinol (THC) exposure. Findings from this work will advance our understanding of the neurobiological and psychiatric consequences of cannabis exposure in TAY. The application builds on the candidate’s prior research experience in characterizing the acute effects of cannabis in dual-disorder patients and examining functional connectivity biomarkers of risk, resilience and treatment response in depression. Over the course of the K23, Dr. Fischer will receive in-depth mentored-training in new areas that are essential to her career development: (1) the multidimensional characterization of reward processing and impairment; (2) the neurobiology of phyto/endo-cannabinoids and the hypothalamic-pituitary-adrenal (HPA) stress axis; and (3) the longitudinal investigation and analysis of translational cannabis and depression research in TAY. An interdisciplinary team of mentors who are experts in the characterization of reward function and impairment in relation to substance abuse (Dr. Knutson), phyto/endo- cannabinoid pharmacology and physiology (Dr. Piomelli), HPA stress-axis physiology and pathophysiology in depression (Dr. Schatzberg), adolescent cannabis research (Dr. Tapert), and statistical methods for analyzing longitudinal data (Dr. Jo) will help the candidate meet her training and research objectives. This program of research and training directly aligns with NIDA and NIMH Strategic Plans and Priorities by rigorously characterizing the neurobiological and psychiatric impact of cannabis exposure during an understudied period of brain development using quantitative, multivariate, and longitudinal assessments. Dr. Fischer’s research and training will take place at Stanford University. This K23 Career Development Award will provide a fundamental foundation for the candidate to achieve her career goals of characterizing the longitudinal effects of cannabis exposure on neurobiological function in relation to clinical symptoms, thereby informing public poloicy and assisting in the development of neurobiologically-guided interventions for cannabis use and depressive disorders.