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Adolescent rats exposed to chronic stress showed fewer signs of depression after receiving the herbal supplement Ashwagandha, according to new research published in Psychopharmacology. The study found that the herb not only eased behavioural symptoms but also reduced inflammation and cell damage in the brain—effects that in some cases surpassed those of the antidepressant sertraline.
Depression during adolescence is becoming increasingly common, yet treatment options remain limited and often come with side effects. Scientists have long known that chronic stress can disrupt brain function by increasing inflammation, damaging nerve cells, and lowering levels of proteins that support healthy brain activity. These biological changes are thought to contribute to the emotional and cognitive symptoms seen in depression.
Ashwagandha, a plant widely used in traditional Indian medicine, has gained attention for its stress-relieving properties. Previous studies in adults and animal models suggest it may help regulate the body’s stress response and protect brain cells. However, until now, no research had examined whether Ashwagandha could help younger individuals, whose developing brains may respond differently to both stress and treatment.
Led by Gul Sahika Gokdemir from Mardin Artuklu University, Turkey, researchers worked with 28 adolescent male rats. Most of the rats were exposed to a 17-day protocol of unpredictable mild stressors—such as wet bedding, overnight food deprivation, and brief restraint—designed to mimic the unpredictable pressures that can contribute to depression.
To properly assess the treatments, some of these stressed rats were left untreated to serve as a depressed baseline, while others received daily oral doses of either sertraline, a commonly prescribed antidepressant, or Ashwagandha. A control group experienced no stress at all.
The team then assessed the animals using standard behavioural tests. Untreated stressed rats showed classic signs of depression: they drank less sweetened water (a measure of reduced pleasure), spent more time immobile during a forced swim test (a sign of despair-like behaviour), and displayed more anxiety-like responses in a maze test. Both sertraline and Ashwagandha improved the treated rats’ performance on the pleasure and despair measures, suggesting strong antidepressant-like effects. Anxiety levels improved slightly but not significantly.
Beyond behaviour, the researchers examined the rats’ brain tissue. Stress sharply increased levels of inflammatory molecules (like TNF-α) and proteins associated with cell death (Bax and Caspase-3). It also reduced levels of BDNF, a protein essential for healthy brain function, and lowered the number of supportive glial cells, known as astrocytes.
Ashwagandha reduced the cell-death markers and inflammation much more effectively than sertraline, returning them to levels similar to the healthy controls, and successfully restored glial cell levels. However, the researchers noted that while Ashwagandha profoundly protected against cell death, its ability to restore the depleted BDNF levels was only borderline. Additionally, the herb prevented the weight loss typically seen in stressed animals, a protective effect that sertraline did not match.
Microscopic examination of the brain revealed that stressed rats showed swelling and structural disruption in the fronto-parietal cortex.
“We focused on the fronto-parietal cortex due to its role in cognitive and emotional processes. This region is involved in attention regulation, decision-making, and emotional control processes and is frequently impaired during depression,” Gokdemir and team noted.
These abnormalities were noticeably reduced in the Ashwagandha-treated group, whose brain tissue more closely resembled that of the healthy controls.
While the findings are promising, the authors caution that the study was conducted only in male adolescent rats, and results may differ in females or humans due to hormonal differences. They also note that the brain region examined was broad, and future work should look at specific subregions to better understand exactly how Ashwagandha exerts its neuroprotective effects.
The study, “Antidepressant-like effects of Ashwagandha (Withania somnifera) on chronic unpredictable mild stress-induced depression in adolescent rats,” was authored by Gul Sahika Gokdemir, Ugur Seker, Nazan Baksi, Mukadder Baylan, Berjan Demirtaş, and Mehmet Tahir Gokdemir.
