A recent study published in the Journal of Affective Disorders suggests that a common blood pressure medication might help reduce anxiety and alter how people pay attention to emotional information. The research indicates that the drug losartan changes how the brain processes distractions, but it appears to affect men and women differently. These findings provide evidence that medications targeting the body’s blood pressure systems might offer new ways to manage anxiety disorders.
Flexible attention is a fundamental part of everyday life. This mental skill, known as attentional control, involves goal-directed regulation, which is the ability to intentionally focus on a specific task. It also involves stimulus-driven capture, which occurs when a sudden or emotionally intense event automatically grabs a person’s attention. A specific part of this system is inhibitory control, which is the mental ability to suppress the urge to react automatically to distractions.
People with anxiety often experience an imbalance between these two attention processes. They tend to be easily distracted by potential threats and have difficulty intentionally shifting their focus away from those stressors. Interventions that improve inhibitory control are considered potential treatments for anxiety. Traditional anxiety treatments, such as certain antidepressants and talk therapy, do not work for everyone, leading researchers to look for new options.
The body possesses a network called the renin-angiotensin system. This system is traditionally known for regulating blood pressure, but it also heavily influences brain areas responsible for emotion and cognitive regulation. The primary chemical messenger in this system acts on specific receptors in the brain. Past animal studies and early human trials suggest that temporarily blocking these receptors with losartan, a standard blood pressure medication, might reduce anxiety and improve a person’s ability to regulate fear.
“Recent animal studies and neuroimaging studies in humans have shown that targeting the angiotensin-renin system can modulate brain circuits related to fear and motivation,” said Benjamin Becker, a professor at the SRT AI, Society and Social Dynamics and the Department of Psychology at The University of Hong Kong. “These receptors can be readily blocked by common blood pressure medications (such as losartan) which specifically block the angiotensin-II type 1 (AT1) receptor.”
The researchers suspected that blocking these receptors might improve focus because they are concentrated in brain regions associated with inhibitory control. In addition, the distribution and activity of these receptors naturally differ between biological sexes, raising the possibility that treatments blocking them might produce sex-specific effects.
“We wanted to find out if the pharmacological blockade also (1) affects cognitive control in healthy humans, this is important to pave the way as new treatment for mental disorders characterized by high fear and anxiety (such as anxiety disorders, PTSD), and whether (2) the effects differ between men and women, which is important for personalized inventions and ultimately the translation into new medical treatments,” Becker said.
To explore these dynamics, the authors conducted a randomized, double-blind, placebo-controlled experiment. They recruited 79 healthy university students, including 39 women and 40 men, between the ages of 18 and 29. The researchers randomly assigned participants to take either a single 50-milligram pill of losartan or a placebo pill. Neither the participants nor the researchers knew who received which pill until the study concluded.
The scientists measured the participants’ anxiety levels using standard questionnaires before the drug was administered and again after the experiment. To measure attentional control, the researchers used an eye-tracking test called an anti-saccade task. During this 40-minute computer task, participants looked at a screen that briefly displayed either emotional faces, such as angry, sad, happy, and fearful expressions, or simple non-social shapes like ovals.
The task had two conditions. In the pro-saccade condition, participants were instructed to look toward the image as quickly as possible, which measures automatic, reflexive attention. In the anti-saccade condition, participants had to look away from the image and focus on the opposite side of the screen. This requires the brain to actively suppress the natural reflex to look at a sudden image, testing top-down inhibitory control.
Using specialized cameras, the scientists recorded exactly where and how quickly the participants moved their eyes. They measured the spatial accuracy of the eye movements in pixels and the reaction time in milliseconds. The researchers also analyzed how the participants’ performance changed from one trial to the next, such as whether they slowed down or became more accurate immediately after making a mistake. The statistical analyses controlled for the participants’ baseline anxiety levels.
The researchers found that the single dose of losartan reduced state anxiety across the entire group, regardless of sex. The losartan group experienced a moderate drop in anxiety from the beginning to the end of the experiment, compared to the placebo group. Because the participants were healthy and took only a single dose, the medication did not produce a statistically significant change in blood pressure.
“The anxiety-reducing effect had a moderate effect size, which is already notable for a single-dose study and in the context of the fact that no new medication for anxiety was approved for about 3 decades,” Becker told PsyPost. “Losartan successfully reduced anxiety across sexes, but its effects on cognitive/attentional control diverged sharply between sexes.”
When looking at the eye-tracking data, the overall rate of looking in the wrong direction did not differ between the losartan and placebo groups. Both groups made more errors when trying to look away from images compared to looking toward them, and they made more errors when looking at social faces compared to simple shapes. However, losartan altered the physical precision and speed of the eye movements in a sex-dependent manner.
For women, losartan improved performance. Women who took losartan had better spatial accuracy when looking away from non-social shapes, missing their target by an average of 108 pixels, compared to women in the placebo group who missed by 131 pixels. Women in the losartan group also exhibited faster reaction times when instructed to look toward objects, and they showed a consistent ability to avoid repeating errors.
For men, the medication had the opposite effect on execution and precision. Men who took losartan were less accurate when looking away from shapes, missing their target by about 160 pixels, compared to the placebo group’s 111 pixels. Men taking the drug also took longer to look away from shape stimuli than men taking the placebo.
This divergence highlights a need for individualized medicine. “Two key takeaways: the drug can help to reduce anxiety in men and women, and as such may be a promising new treatment for mental disorders, but the underlying cognitive effects on attentional control differed in men versus women,” Becker said. “This highlights that future treatments for anxiety and attention-related disorders cannot rely on a one-size-fits-all approach; instead, they need to be tailored to individual biological characteristics.”
Beyond overall accuracy, the research team used computational methods to examine how participants adjusted their behavior from one moment to the next. In both men and women, the medication improved how they responded right after an incorrect trial. “Our new computational analyses revealed that losartan significantly lowered error probability immediately AFTER a preceding error, meaning the drug enhanced real-time self-correction which is a quite interesting mechanism and can improve flexible adaptation,” Becker said.
This ability to adjust based on immediate past experience was not apparent when looking only at average error rates over the entire task. “This effect was entirely masked when only looking at the overall averages,” Becker added. Men taking losartan, however, were more likely to make errors immediately following a correct trial compared to men on the placebo, suggesting some behavioral rigidity mixed with this self-correction.
These moment-to-moment adjustments provide a deeper look at how the brain manages focus. “Second, we used computational methods to better understand the behavior and could show that the treatment specifically improved behavior right after making a mistake,” Becker said. “This is interesting because cognitive control isn’t just about making fewer errors, but also to rapidly adapt after mistakes and improve.”
The study’s lead author emphasized this dynamic aspect of brain function. “Cognitive improvement is not just about overall performance, it’s about learning from mistakes and adapting in real time,” said Mengfan Han, a PhD student and the study’s first author.
These findings indicate that blocking the renin-angiotensin system can reduce anxiety, but doing so alters cognitive control differently depending on biological sex. The study relied on a single dose of the medication in healthy young adults. A single dose does not reflect how the brain might adapt to taking the medication daily over weeks or months. This is an important distinction because psychiatric and cardiovascular treatments typically involve long-term use.
“From single-dose effects in healthy volunteers to actual clinical application, some work remains, including long-term safety validation, patient populations and optimal dosage determination,” Becker said. The study also did not include direct brain imaging. While the eye-tracking metrics provide precise behavioral data, the researchers could not observe the actual neural circuits firing in real time.
Future research will need to image the brain to see exactly how losartan alters the communication between the prefrontal cortex and emotional centers. To address these unknowns, the researchers are planning follow-up studies. “To determine some of these aspects we recently started a clinical trial in patients with mental disorders and hope to move closer to translation into applications for mental health,” Becker said. “Our broader goal is to build a clear path from lab discoveries to real-world personalized treatments for cognitive and emotional disorders, our ongoing clinical trials can hopefully move us closer to novel treatments in mental disorders.”
The study, “Angiotensin II regulates anxiety and social-affective top-down and bottom-up attention control in a sex-dependent manner,” was authored by Mengfan Han, Kun Fu, Wenyi Dong, Junjie Wang, Dan Liu, Qian Zhuang, Xiaolei Xu, Stefania Ferraro, Ting Xu, Keith M. Kendrick, Dezhong Yao, Wing Chung Chang, and Benjamin Becker.
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