A randomized clinical trial published in JAMA Network Open found that a single 10 mg dose of oral hydrocortisone was associated with improved attention and verbal learning within hours in women with virally suppressed HIV. Four weeks of daily treatment was also linked to better delayed memory recall.
The study included 81 women with HIV, with an average age of 55. Most participants identified as Black or African American. All reported experiencing stress, a mood or anxiety disorder, or both, and showed measurable impairment in at least one area of cognitive function.
Researchers, including Leah H. Rubin, Ph.D., M.P.H., of Johns Hopkins University, focused on the hypothalamic-pituitary-adrenal (HPA) axis, the body’s main stress-response system. Chronic stress and psychiatric conditions can affect this system and may contribute to cognitive difficulties. Because hydrocortisone is chemically identical to cortisol, the researchers investigated whether a low dose could influence this pathway and improve cognitive performance.
The trial was conducted in two stages. First, participants received a single 10 mg dose of hydrocortisone or placebo and completed cognitive tests 30 minutes and four hours later. After 30 minutes, hydrocortisone did not significantly improve the main measures of verbal learning and memory, working memory or visuospatial skills. Attention, however, improved. Four hours after treatment, verbal learning showed a significant improvement, while the change in delayed recall fell just short of statistical significance. Cortisol levels reached their highest point around 75 minutes after dosing.
During the second stage, participants took hydrocortisone or placebo daily for four weeks. Those receiving hydrocortisone experienced a significant improvement in delayed recall, while the placebo group did not. However, the difference between the two groups was not statistically significant, so the researchers could not conclude that hydrocortisone was more effective than placebo.
The team also investigated several biological markers, including measures related to hormones, inflammation, glucocorticoid receptors and the HIV reservoir. None explained the cognitive changes observed.
The treatment was considered safe and well tolerated, with no serious adverse events or clinically meaningful changes in metabolic, liver or HIV-related measures.
The researchers said the findings indicate that temporarily altering HPA-axis activity may improve certain cognitive abilities, particularly attention, verbal learning and memory, in people affected by chronic stress and cognitive impairment.
They stressed that low-dose hydrocortisone is not intended to replace established non-drug approaches such as cognitive behavioral therapy, exercise, sleep improvement and stress-management strategies. Instead, the findings could help guide research into future treatments that combine different approaches.
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