The Rescue Potential of Cannabidiol and β-Caryophyllene Against the Molecular Changes Induced by Early Life Stress in Mice

Early life stress (ELS) encompasses a variety of negative life events and circumstances that have persistent effects on physical and mental health in adulthood. Inaccessible and ineffective interventions make managing these symptoms a challenge, indicating the need for a different pharmacological approach with a novel pharmacodynamic. Cannabidiol (CBD), the prominent non-intoxicating component of Cannabis Sativa L., has shown therapeutic potential in addressing many of the pathologies associated with ELS, including anxiety, depression, elevated inflammation, and poor synaptic health. The addition of other compounds produced by the cannabis plant, including terpenes, is hypothesized to synergistically enhance the therapeutic benefits of CDB. In this study, I investigated the rescue potential of CBD and β-caryophyllene (BCP), a cannabis-derived terpene, on brain derived neurotrophic factor (BDNF), a protein involved in synaptic support, and tumor necrosis factor α (TNF-α), an inflammatory marker, in the prefrontal cortex (PFC) and hippocampus. Mice underwent 3 hours of maternal separation (MS) for 16 days, followed by 15 days of exposure to one of four intervention conditions (CBD, BCP, CBD + BCP, or Vehicle), administered through voluntary consumption. Mice who underwent MS followed by exposure to both CBD and BCP showed elevated BDNF and TNF-α signaling in the PFC, but not the hippocampus. In partial support of my hypothesis, the combination of CBD and BCP rescued the effects MS had on synaptic support through elevated BDNF signaling, but did not rescue the neuroinflammatory effects of MS, evidenced by elevated levels of TNF-α. These results suggest a region-dependent rescue effect of CBD and BCP on BDNF signaling, providing support for its use in addressing some, but not all effects of ELS. Additionally, these results contribute to the growing body of research evaluating the effectiveness and safety profile of CBD-based therapy on the developing brain.