Reykjavik, Iceland – Researchers at Reykjavik University have identified the neural mechanism engaged by amlodipine, a widely used blood pressure medication, as holding promise for the development of new treatments for attention-deficit/hyperactivity disorder (ADHD). The findings, published in Neuropsychopharmacology, highlight strong scientific evidence supporting the potential of targeting L-type calcium channels (LTCCs) in ADHD treatment, rather than using amlodipine in its current form. This research marks an important step forward in addressing gaps in current ADHD therapies.

ADHD is a common neurodevelopmental disorder, yet treatment options remain limited. While stimulant medications like methylphenidate are effective for many patients, they often cause side effects, have a high non-response rate, and carry a risk of misuse. In collaboration with international partners, RU scientists explored alternative approaches and found that targeting LTCCs could provide a safer and well-tolerated treatment option.

The study combined multiple advanced research methods, including behavioral experiments in animal models, genetic analysis, and real-world patient data. Key findings include:

• Behavioral Improvement in ADHD Models – Amlodipine’s mechanism reduced hyperactivity in Spontaneously Hypertensive Rats, a widely used model for ADHD, and improved impulsivity in zebrafish engineered to mimic ADHD symptoms. These results provide strong cross-species validation of the therapeutic potential of LTCC modulation.
• Blood-Brain Barrier Penetration – Penetration assays confirmed that amlodipine and similar compounds can cross the blood-brain barrier and affect neural activity, challenging prior assumptions about their limited brain penetration.
• Genetic Link to ADHD – Mendelian Randomization analysis and genetic studies linked ADHD to calcium channels in the brain (CACNA1C, CACNB1, CACNA2D3), reinforcing the potential of LTCC-targeting drugs in ADHD treatment.
• Human Data Supports ADHD Symptom Reduction – A study of UK Biobank data showed that individuals with a high genetic risk for ADHD who were prescribed amlodipine exhibited reduced ADHD-related symptoms, suggesting real-world therapeutic benefits from LTCC modulation beyond its use for hypertension.

Dr. Karl Karlsson, Professor of Biomedical Engineering at Reykjavik University and co-author of the study, emphasized the significance of the findings:

"This research represents a major step forward in ADHD treatment. Our findings suggest that targeting L-type calcium channels, a mechanism influenced by amlodipine, could be the basis for a non-stimulant ADHD treatment. By leveraging this insight, we may be able to develop effective and accessible medications for ADHD much sooner than starting from scratch."

Building on these results, the researchers at Reykjavik University are advancing investigations into LTCC-modulating drugs, and formulations thereof with the goal of validating their effectiveness in human trials. This discovery underscores the potential of repurposing existing pharmacological insights to address unmet medical needs and improve patient outcomes.

Link to the full study: https://www.nature.com/articles/s41386-025-02062-x