CBD Reduced Depression-Like Behavior and Brain Inflammation in Female Rats Exposed to Stress and a High-Fat Diet

Female rats exposed to both a high-fat diet (2 weeks) and chronic unpredictable mild stress (4 weeks) received CBD (10 mg/kg) during the final 2 weeks. CBD promoted active coping behavior, increased locomotion, reduced freezing, and restored depressive-like behavior in the splash test. In the prefrontal cortex, CBD normalized stress-induced increases in IL-1 beta and downregulated NF-kB1 and TNF-alpha expression.

Female Wistar rats exposed to 2 weeks of high-fat diet followed by 4 weeks of unpredictable chronic mild stress. CBD (10 mg/kg, i.p.) or vehicle administered during the last 2 weeks. Behavioral testing and mRNA analysis of inflammatory markers in prefrontal cortex and hippocampal CA1.

Depression and obesity frequently co-occur and share neuroinflammatory mechanisms. This study uses female rats specifically, addressing a major gap since most preclinical depression research uses males. The finding that CBD's effects depend on stressor type has implications for understanding when CBD might be most beneficial.

The finding that CBD's efficacy depends on the type of stressor suggests it may be more helpful for certain depression subtypes than others. The focus on female subjects and the obesity-depression comorbidity addresses two major gaps in current CBD research.

Animal study in female rats only. Single CBD dose tested. Short treatment duration. Intraperitoneal injection, not oral administration. Artificial stress model may not fully capture human depression.