Project Grant F31DA067202

TRANSLATIONAL INVESTIGATION OF CANNABIS-INDUCED COGNITIVE FLEXIBILITY IMPAIRMENT - PROJECT SUMMARY/ABSTRACT RAPID CHANGES IN STATEWIDE LEGISLATION HAVE DRAMATICALLY EXPANDED PUBLIC ACCESS TO RECREATIONAL CANNABIS, THEREBY INCREASING RATES OF DAILY USE. YET, THE ACUTE EFFECTS OF CANNABIS INTOXICATION ON COGNITIVE AND NEUROBIOLOGICAL OUTCOMES REMAIN POORLY UNDERSTOOD. THERE IS SOME EVIDENCE SUGGESTING HIGHER-ORDER COGNITIVE SKILLS INCLUDING EXECUTIVE FUNCTIONS SUCH AS COGNITIVE FLEXIBILITY MAY BE SENSITIVE TO ACUTE CANNABIS INTOXICATION, BUT EXISTING RESEARCH IS LIMITED, INCONSISTENT, AND OFFERS LITTLE MECHANISTIC INSIGHT. PREFRONTAL CORTEX (PFC) GAMMA OSCILLATIONS, INFLUENCED BY PARVALBUMIN-POSITIVE INTERNEURONS (PV), ARE CRITICAL MODULATORS OF COGNITIVE FLEXIBILITY, YET NO STUDIES TO DATE HAVE EXAMINED HOW ACUTE CANNABIS INTOXICATION AFFECTS THESE PROCESSES. OUR PRELIMINARY DATA INDICATE THAT ACUTE CANNABIS VAPOR EXPOSURE REDUCES PFC GAMMA POWER, AND THAT INTRINSIC PV PROPERTIES ARE ALTERED DURING COGNITIVE FLEXIBILITY TASK PERFORMANCE IN RATS WITH A HISTORY OF CANNABIS EXPOSURE. THE PROPOSED RESEARCH WILL BE THE FIRST TO USE PARALLEL CLINICAL AND PRECLINICAL AIMS TO CLARIFY HOW CANNABIS INFLUENCES COGNITIVE FLEXIBILITY BY INTERROGATING ITS NEUROBIOLOGICAL UNDERPINNINGS USING TRANSLATIONALLY RELEVANT APPROACHES. AIM 1 WILL ASSESS THE EFFECTS OF VAPORIZED CANNABIS ON COGNITIVE FLEXIBILITY (WISCONSIN CARD SORTING TASK [WCST]) AND OTHER EXECUTIVE FUNCTIONS IN HUMANS. FRONTAL EEG RECORDINGS WILL BE USED TO QUANTIFY CORTICAL OSCILLATIONS DURING TASK PERFORMANCE, AND I WILL EXAMINE WHETHER OBSERVED EFFECTS ARE MODERATED BY SEX AND CANNABIS USE HISTORY. AIM 2 WILL USE A RODENT ATTENTIONAL SET-SHIFTING TASK THAT PARALLELS THE WCST USED IN AIM 1, ALONG WITH PV CELL-SPECIFIC FIBER PHOTOMETRY TO DETERMINE HOW ACUTE CANNABIS VAPOR EXPOSURE ALTERS PV ACTIVITY IN THE MEDIAL PFC DURING TASK PERFORMANCE. A MULTIPLE GROUP DESIGN WILL ALLOW ME TO TEST POTENTIAL MODERATING ROLES OF SEX AND CANNABIS EXPOSURE HISTORY. THIS WORK WILL PROVIDE CRITICAL PUBLIC HEALTH INSIGHT AS CANNABIS POLICY CONTINUES TO EVOLVE. BEYOND ADVANCING SCIENTIFIC KNOWLEDGE, THIS FELLOWSHIP INVOLVES AN INTEGRATED TRAINING PLAN SPECIFICALLY TAILORED TO DEVELOP MY SKILLS AND EXPERTISE AS A TRANSLATIONAL COGNITIVE NEUROSCIENTIST. I WILL RECEIVE ADVANCED TECHNICAL TRAINING, COMPLETE COURSEWORK IN QUANTITATIVE ANALYSES, AND ENGAGE IN SPECIFIC PROFESSIONAL DEVELOPMENT OPPORTUNITIES TO ENHANCE MY SCIENCE COMMUNICATION AND MENTORSHIP ABILITIES. I WILL CONDUCT THIS WORK WITHIN A HIGHLY COLLABORATIVE AND WELL-EQUIPPED RESEARCH ENVIRONMENT AT WASHINGTON STATE UNIVERSITY. ADDITIONALLY, I HAVE THE PRIVILEGE OF COMPLETING THIS RESEARCH IN A HIGHLY UNIQUE TRAINING ENVIRONMENT, WHERE I WILL RECEIVE DETAILED MENTORSHIP FROM DR. CUTTLER AND DR. MCLAUGHLIN IN RIGOROUS CLINICAL AND PRECLINICAL METHODOLOGIES. COLLECTIVELY, THE PROPOSED RESEARCH AIMS, TRAINING ACTIVITIES, AND ENVIRONMENT WILL PROVIDE THE HOLISTIC PREPARATION AND GUIDANCE NEEDED FOR MY DEVELOPMENT INTO A SUCCESSFUL INDEPENDENT RESEARCHER CAPABLE OF BRIDGING MECHANISTIC AND APPLIED APPROACHES TO UNDERSTANDING COGNITION.