Lost in Translation: Using Animal Models to Investigate the Effects of Developmental Cannabis Exposure
A foremost public concern regarding the recent wave of cannabis legalization has been the increased risk of potentially adverse neurodevelopmental outcomes. Daily cannabis use is becoming more prevalent among adolescents and cannabis use during pregnancy is quickly becoming a major public health concern. However, the effects of cannabis on the developing brain remain largely unknown, in part because longitudinal human studies are very cost- and labor-intensive and cross-sectional studies are plagued by confounding environmental factors that can complicate interpretation of the data. Animal models provide an opportunity to examine effects of developmental cannabis exposure in a more controlled, systematic fashion within a feasible time scale. However, current approaches fail to accurately model the drug and route of administration most common to human users, which limits the translational value of the results. In our laboratory, we have developed a novel preclinical model of response-contingent cannabis exposure that uses vaporized delivery of whole plant cannabis extracts containing high concentrations of Δ9 tetrahydrocannabinol (THC) or cannabidiol. We have recently shown that THC-rich cannabis vapor has robust reinforcing properties, supports conditioned drug-seeking behavior, and produces biologically relevant cannabinoid concentrations in rat plasma and brain tissue. In this seminar, I will discuss new data from our laboratory wherein we have used this model to investigate the long-term effects of prenatal and adolescent cannabis exposure on emotional, cognitive, and neurobiological outcomes. Our results reveal profound alterations in emotional reactivity in cannabis-exposed offspring across the lifespan and sex-dependent effects on cognitive flexibility and prefrontocortical white matter development following adolescent cannabis self-administration. Together, these studies further establish the response-contingent cannabis vapor delivery model as a viable means to assess the effects of cannabis use on the brain and behavior and indicate potentially deleterious effects of cannabis exposure on the developing brain.