Single Dosage of Psychedelic Compound Enhances Brain Flexibility for Weeks, Study Reveals

Recent research from the University of Michigan has demonstrated that administering a single dose of a psychedelic substance can significantly improve cognitive flexibility—the brain's capacity to adapt to new situations—for an extended period of several weeks. This breakthrough finding suggests potential new avenues for treating mental health conditions such as depression, PTSD, and neurodegenerative diseases.

The study, titled "Single-dose psychedelic enhances cognitive flexibility and reversal learning in mice weeks after administration," focused on the effects of 25CN-NBOH, a selective serotonin 2A receptor agonist. Researchers found that mice treated with this compound displayed notable improvements in reversal learning task performance, even two to three weeks post-treatment, compared to control mice. Key indicators included better task efficiency, higher correct trial percentages, and increased reward collection during reversal phases.

Lead researcher Professor Omar J. Ahmed explained that the significance of these results lies in the lasting nature of the cognitive benefits observed after just a single psychedelic dose. "We observed enhanced learning adaptability that persisted for weeks, implying these compounds may induce durable and meaningful neuroplasticity changes within the prefrontal cortex," he said.

The experiments utilized an innovative automated sequential learning paradigm to assess cognitive flexibility, which measured how effectively mice adapted to changing rules. The mice receiving psychedelic treatment outperformed controls, showcasing superior flexibility.

These findings add to existing evidence of cellular-level brain remodeling caused by psychedelics, especially in the prefrontal cortex, but uniquely highlight sustained cognitive enhancements long after the drug’s immediate effects wear off. This raises compelling questions about how psychedelics could potentially reopen critical periods of brain plasticity and the underlying molecular mechanisms for such long-term improvements.

Further research is necessary to determine how repeated doses or varying dosing schedules might influence neuroplasticity and cognitive function over time. Dr. Ahmed emphasized the importance of understanding the effects of multiple doses over months to optimize therapeutic protocols.

Importantly, the study observed similar benefits in both male and female mice, indicating the broad potential of psychedelic treatments across sexes. Elizabeth J. Brouns, the study's first author, noted that the ability of a single dose to produce lasting benefits suggests that psychedelics may induce fundamental and beneficial changes in brain function.

This research advances the development of targeted psychedelic therapies, with high-throughput behavioral assessments enabling faster evaluation of cognitive flexibility. Such innovations could accelerate progress toward effective treatments for cognitive deficits linked to various mental health conditions.

Source: https://medicalxpress.com/news/2025-04-dose-psychedelic-boosts-brain-flexibility.html