Impact of Cannabinoid Across the Lifespan (ICAL)

ICAL ANALYTICAL CORE: SUMMARY The NIDA Center of Excellence Impact of Cannabinoids Across the Lifespan (ICAL), whose renewal is proposed in this revised application, tests the hypothesis that non-physiological activation of the endocannabinoid system during adolescence – caused by exposure to D9-tetrahydrocannabinol (THC) – initiates a reprogramming of the genetic and epigenetic processes that govern this system’s molecular structure, neuroanatomical architecture, and synaptic functions, ultimately producing persistent abnormalities in cognition and motivated behavior. In the first funding period, which lasted 4 years, the Analytical Core conducted nine studies which (1) systematically characterized drug metabolism and pharmacokinetic properties of THC in adolescent and adult mice and rats of both sexes; and (2) provided pharmacokinetic and pharmacodynamic evidence that ICAL’s treatment protocol is a realistic surrogate for daily cannabis use in teenagers. The studies have produced eight publications and two articles in preparation. In this resubmission of ICAL’s renewal application, the Analytical Core has two specific aims. Aim 1: Provide bioanalytical support to ICAL activities. As in the previous funding period, the Core will continue to fulfill requests for endocannabinoid and THC analysis made by ICAL’s Animal Core, Projects, pilot grantees, and external collaborators. Aim 2: Develop a novel highly sensitive method for endocannabinoid analysis and will apply this method to the emerging needs of ICAL’s Projects. The Core will be directed by Dr. Faizy Ahmed, who has >30 years of experience in analytical chemistry with emphasis on liquid chromatography-tandem mass spectrometry (LC-MS/MS). His primary responsibilities will be to: (i) implement LC-MS/MS methods for the quantification of THC, its metabolites, and endocannabinoid lipids in tissues; (ii) develop, validate and test an innovative LC-MS/MS assay for the quantification of trace endocannabinoid lipids in relevant biomaterials; (iii) schedule shared use and maintenance of LC-MS/MS instrumentation; (iv) supervise a Senior Staff Research Associate responsible for sample preparation; and (v) train graduate students and postdoctoral scholars in the use of LC-MS/MS equipment for THC and endocannabinoid analysis.