Ketamine in Adolescence: New Study Reveals Lasting Effects on Brain Development and Paves the Way for Potential Treatments

Original article: Ketamina en la adolescencia: Nuevo estudio determinó sus efectos en el cerebro y abre la puerta a posibles tratamientos para revertir el daño Ketamine in Adolescence: New Study Reveals Lasting Effects on Brain Development and Paves the Way for Potential Treatments Adolescence is a critical stage for developing the prefrontal cortex, the area of the brain that regulates processes such as planning, focus, and directing behavior towards specific goals. Recently, a team of Chilean researchers made a significant breakthrough in understanding the impact of drugs on the brain development of young individuals. The study found that the use of ketamine—one of the most commonly abused substances among adolescents in the country—permanently alters the prefrontal cortex, which is responsible for decision-making and complex thought processing.

Marco Fuenzalida, a researcher with the Neuroepigenetics and EpiNeuro Plasticity Center and a professor at the University of Valparaíso, who led the study, explained that the results indicate that ketamine acts as an antagonist of NMDAR receptors, critical ion channels in the nervous system. Its consumption during adolescence leaves a lasting mark on prefrontal circuits in adult subjects. This occurs because it diminishes inhibition mediated by GABAergic interneurons (key inhibitory neurons in the central nervous system) of the Parvalbumin-positive (PV) type, leading to a deterioration of synaptic plasticity in the prefrontal cortex.

The research took three years of theoretical and experimental work, utilizing electrophysiological tools (patch-clamp) to record the activity of individual neurons, pharmacology, AI-based synaptic transmission analysis, and genetically modified laboratory models. The Next Step: Reversing the Damage After identifying the issue, scientists are already working on solutions. Currently, the laboratory is using «chemogenetic» techniques (artificially designed receptors that activate with drugs) and specific neuronal modulators to reactivate these damaged interneurons.

Early results in the lab are promising: the team has already achieved activity in PV interneurons. The next phase of the research will focus on applying these tools in laboratory models to attempt to completely reverse cognitive and memory damage caused by ketamine use during youth. The research team at the University of Valparaíso included Felipe Guiffa-Gómez, Sashá van Buuren, Freddy Aguilar, Juan Ahumada, Angélica Escobar, Ramón Sotomayor-Zárate, Koyam Morales-Weil, and Marco Fuenzalida as the study leader.