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Breaking the Grass Ceiling: CBD Improves Female Depression
The microbiome is highly susceptible to change in many chronic conditions. Chief among these are obesity and depression, which are often found hand-in-hand. Researchers are increasingly pointing to inflammation in the brain as a possible link between them. A new study from scientists at the University of Haifa found that cannabidiol (CBD), a non-psychoactive compound from cannabis, might help improve mood and reduce brain inflammation in females facing both a poor diet and chronic stress.
In this study, female rats were fed a high-fat diet for two weeks and then exposed to four weeks of unpredictable chronic mild stress (UCMS)—a common model of depression in animal research. The high-fat diet is interesting here, since it has been shown to severely disrupt the microbiome. During the last two weeks of stress, the rats were treated with either CBD or a placebo. The team tested the rats’ behavior using a suite of assessments for depression, anxiety, and social interaction. They also examined changes in gene expression in brain regions linked to emotional regulation: the ventromedial prefrontal cortex and a part of the hippocampus called CA1.
The results showed that CBD had meaningful behavioral effects, but they were dependent on the rats’ stress exposure. For rats facing both a high fat diet and stress, CBD helped reduce depression-like symptoms. In the forced swim test, for example, CBD-treated rats showed more active coping behaviors (like climbing) and less immobility, suggesting improved mood and resilience. In the splash test (which measures how often they groom themselves), CBD reversed the stress-induced decline in self-care. That decline is another marker of depression-like behavior.
CBD also had mixed effects on anxiety-like behavior. In groups exposed to either only a high fat diet or only stress, it increased exploratory activity and decreased freezing, a sign of reduced anxiety. However, in rats exposed to both a high fat diet and stress, CBD only restored to baseline in some cases. This suggests that CBD may be more effective for mild or single sources of stress, and that its role shifts in more complex, compounded stress conditions.
What’s happening in the brain to explain these changes? The researchers looked closely at inflammatory gene markers. In the brains of rats exposed to both stressors, CBD lowered the expression of IL-1β, NF-κB1 and TNF-α. These are molecules that normally trigger an inflammation response. CBD seemed to help “cool down” inflammation in parts of the brain responsible for emotional processing, especially under high-stress conditions. These patterns support the idea that neuroinflammation may play an active role in shaping behavior and mood.
Unlike many studies that focus on male rodents, this one was done entirely in females. This is an important step, since depression and obesity are more common in women and female animals often respond differently to stress. The researchers note that while the behavioral effects of stress-induced depression were milder in females, CBD still had significant impacts, especially when inflammation was high.
As with all animal studies, the results aren’t directly transferable to humans, but they do point toward potential applications. CBD is already being explored for anxiety and mood disorders, and this study suggests it might be especially helpful in stress-related conditions where inflammation is involved, such as depression linked to poor diet or chronic life stressors.
In the end, this research doesn’t claim CBD is a magic bullet. But it does offer strong support for its ability to improve mood and reduce brain inflammation in this particular “double-hit” model of diet and stress. For anyone studying how lifestyle, mental health, and biology intersect, this study brings us one step closer to understanding how cannabis-based therapies might fit into future treatments.
Link to the original post: Sabbag, T., Kritman, M., & Akirav, I. (2025). Cannabidiol Effects on Depressive-like Behavior and Neuroinflammation in Female Rats Exposed to High-Fat Diet and Unpredictable Chronic Mild Stress. Cells, 14(12), 938.
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Featured image: Created by the author using Canva Pro.
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