Alyssa Tollefson

Cannabis is one of the most commonly used drugs, and legalization has been on the rise in the US (40 states allow medicinal use, 24 states allow small recreational use). Though a common misconception is that cannabis is not addictive, cannabis use disorder (CUD) is recognized by the DSM-V. 10% of adults who use cannabis and over 16% of people who start using cannabis before the age of 18 develop CUD. While cannabis research is well documented, the genetic factors that contribute to CUD are complex, rodent research is highly variable, and we do not yet know what makes people vulnerable to CUD. The cannabinoid tetrad is a well established test of cannabis effects, specifically hypolocomotion, hypothermia, catalepsy, and analgesia. Our goal is to use this cannabinoid tetrad with genetically diverse heterogeneous stock (HS) rats to survey the range of physiological effects of delta-9-tetrahydrocannabinol (THC) in a way that better mimics the human population. We predicted dose-dependent decreases in locomotion and body temperature and dose-dependent increases in catalepsy and analgesia. We found significant decreases in locomotion at the 10 mg/kg THC dose, and significant decreases in catalepsy at the 30 mg/kg THC dose. Though downward trends were observed for both of these groups in these assays, the HS rats generally exhibited great variability throughout the doses and assays. This suggests that drug-naive variability may overpower some of the expected tetrad responses. This work highlights the importance of individual and genetic variation on pharmacological effects, and will inform future rodent cannabinoid research.