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Research team at the Medical Center - University of Freiburg deciphers in an animal model how a ketamine-like substance acts against depression in the brain/ Basis for targeted development of new drugs

A research team from the Department of Psychiatry and Psychotherapy at the Medical Center - University of Freiburg has discovered a promising new mechanism that could enable the development of fast-acting antidepressants. The study, published in the journal Nature Communications on November 26, 2025, focuses on the active substance NAB-14, which the researchers were able to show blocks a specific receptor in the brain that is involved in the transmission of nerve signals and is considered a possible key factor in depression much more specifically than ketamine. Unlike ketamine, however, there are no intoxicating side effects. The results could pave the way for more targeted and better tolerated treatment options for people with depression.

"In animal studies, the active ingredient NAB-14 showed a rapid antidepressant effect that lasted up to two days. This is a promising approach for patients for whom conventional therapies have so far not helped sufficiently," says study leader Prof. Dr. Claus Normann, Section Head in the Department of Psychiatry and Psychotherapy at the Medical Center - University of Freiburg. The researchers are currently preparing the application of NAB-14 in humans.

NAB-14: Like ketamine, but without the high

NAB-14 targets a specific component of the NMDA receptor in the brain, which plays a central role in communication between nerve cells. By blocking the so-called GluN2D subunit, the active ingredient specifically influences the balance between activating and inhibiting signals in the brain. In animal models, this led to a rapid improvement in depression-like behaviors. At the same time, NAB-14 showed significantly less evidence of adverse side effects than ketamine, which also acts quickly but often causes restlessness or changes in perception. For this reason, ketamine can only be administered in surgeries or hospitals.

The first steps towards developing NAB-14 as a clinically applicable drug have already been implemented with funding from the Federal Ministry of Research, Technology and Space and the Else Kröner-Fresenius Foundation. The study is part of a translational research program at the Medical Center - University of Freiburg, which is dedicated to the development of novel treatment strategies for depression.

Link to the study: www.nature.com/articles/s41467-025-66774-w