INVESTIGATOR: Jamie Inman, Ph.D.

STUDY LOCATION: Lawrence Berkeley National Laboratory

PROJECT TITLE: Contribution of genetic factors to individual differences in anxiety in response to the cannabinoids THC and CBD

FUNDING SOURCE: Center for Medicinal Cannabis Research

PROJECT TYPE: Pre-Clinical Study

STATUS: Active 

ABSTRACT:

The cannabis policy landscape has dramatically changed recently, and more than 20% adolescents reported using marijuana at least once in the past month. Investigating the beneficial effects of CBD during adolescence is of interest. For example, one in every ten high school seniors has had some exposure to the anxiolytic benzodiazepine and prescriptions have nearly doubled over the past two decades. CBD presents a far safer alternative. However, the mechanistic effects of CBD across the population and potential sex dependent effects needs to be further explored, especially considering that millions of Americans are already using it. The main and most potent psychoactive ingredient in cannabis is the cannabinoid ?9-tetrahydrocannabinol (THC). An additional cannabinoid present in cannabis is cannabidiol (CBD). Genetic studies show that there is a strong genetic component that contributes to the differences between individuals in their response. The underlying mechanisms that contribute to the variation in the response to cannabis and cannabinoids is not well understood. Our study fills this research gap by determining the genetic basis for interindividual response to THC and CBD using a well-controlled, genetically defined population-based mouse model system. We propose to (i) delineate genetic variation that underlies the adverse and/or beneficial effects of THC and CBD on anxiety, and (ii) mechanistically investigate the differential response to THC and CBD by analyzing CBD-altered liver and hippocampal transcript profiles. We will first investigate genetic susceptibility to adverse and/or beneficial effects on anxiety of repeated cannabinoid exposure using a genetically diverse Collaborative Cross (CC) mouse population. We will then delineate the molecular mechanisms that contribute to cannabinoid exposure mediated effects on anxiety using RNA-sequencing of hippocampal tissues from cannabinoid sensitive and resistant CC strains. In summary, in this proposal we will implement a comprehensive strategy using a mammalian population model system that has the potential to serve as a surrogate for the human cannabinoid response. The results will discover novel THC and CBD regulatory genes, and will provide additional data on the effects of THC and CBD on liver and hippocampal transcript profiles. Together these results will facilitate identification of those most likely to benefit from cannabinoid treatment.