Project Summary/Abstract Understanding individual differences in the vulnerability to drug abuse is an important component to developing better prevention and treatment strategies. Evidence indicates that personality traits such as “novelty-seeking” or “sensation-seeking” can influence drug use. The rodent environmental enrichment paradigm has been shown to reliably induce a behavioral phenotype that models the increased drug abuse vulnerability seen with the novelty-seeking personality trait. In this enrichment model, rats are raised in environments with either high or low levels of novelty throughout early adolescence and through adulthood. Rats exposed to high levels of novelty (enriched rats) are consistently found to be less sensitive to low doses of various drugs of abuse compared to rats exposed to low levels of novelty (impoverished rats) when tested in young adulthood. When using this model, the altered sensitivity to drugs of abuse is traditionally not tested until the animals reach adulthood. A more systematic investigation on when during adolescence exposure to high- or low-novelty environments induces these altered behavioral phenotypes is warranted. This may be particularly important as the peak of when people initiate cannabis use is during adolescence. Given the popularity of cannabinoid drugs, it is surprising that there is little to no research investigating whether environmental enrichment can alter sensitivity to marijuana. While delta-9-Tetrahydrocannabinol (delta-9-THC) is considered the major psychoactive ingredient of marijuana, the passage of the 2018 “Farm Bill” has led to the rise in the popularity of minor cannabinoids of the hemp plant including delta-8-Tetrahydrocannabinol (delta-8-THC) and cannabidiol (CBD). Products containing delta-8-THC have recently skyrocketed in popularity, particularly in states where delta-9-THC remains fully illegal. A main goal of the proposed research is to combine new research from our lab looking at the abuse liability of vaped or pulmonary administration of delta-8-THC and CBD and combinations of these compounds using a conditioned place preference (CPP) procedure and determine when and if adolescent environmental enrichment exposure can alter the sensitivity to these cannabis drugs. A second goal is to determine when and if adolescent environmental enrichment exposure may alter brain cannabinoid receptor densities in key brain structures involved in the rewarding and behavioral effects of cannabinoid drugs.