A new study published in the journal Neuropharmacology and conducted by researchers from the University of São Paulo reports that cannabidiol (CBD) may help improve the effects of antidepressant treatment and may do so more quickly than some conventional options.

The study focused on male mice subjected to chronic stress, a commonly used model for studying depression- and anxiety-related symptoms. Researchers found that CBD at a dose of 30 milligrams per kilogram produced behavioral improvements within seven days. By comparison, a high dose of escitalopram, a commonly prescribed SSRI antidepressant, took 14 days to produce similar improvement.

The researchers also found that a lower dose of CBD that was initially ineffective on its own became useful when paired with escitalopram. In stressed mice, the combination of low-dose CBD and escitalopram enhanced anti-stress effects after 10 or 21 days of chronic unpredictable stress, suggesting CBD may have value as an add-on treatment rather than just as a standalone option.

According to the study, the combination appeared to work through changes involving N-acyl phosphatidylethanolamine phospholipase, or NAPE-PLD, in the prefrontal cortex, a brain region involved in mood regulation and stress response. Chronic stress reduced expression of this enzyme, but the CBD and escitalopram combination restored it. The treatment’s effects disappeared in mice that lacked NAPE-PLD, including those genetically altered to remove it specifically from the prefrontal cortex.

Researchers also found that the combined treatment increased NAPE-PLD expression in parvalbumin interneurons in the prefrontal cortex, which they say may help restore the balance between inhibitory and excitatory brain signaling disrupted by chronic stress.

The findings add to a growing body of research indicating that CBD may have therapeutic potential in psychiatric disorders, particularly as a way to enhance existing treatments. Although the results are limited to animal models and do not prove the same effects would occur in humans, the study’s authors say CBD may eventually prove useful as an add-on therapy to improve the action of SSRI antidepressants.