Psychedelic Sparks Long-Term Brain Plasticity – Neuroscience News
2025-04-23T14:01:08Z
A single dose of the psychedelic compound 25CN-NBOH significantly improved cognitive flexibility in mice, with effects lasting up to three weeks post-treatment.
Summary: A single dose of the psychedelic compound 25CN-NBOH significantly improved cognitive flexibility in mice, with effects lasting up to three weeks post-treatment. Treated mice adapted more quickly in rule-switching tasks, indicating enhanced neuroplasticity in the prefrontal cortex.
The findings suggest psychedelics may offer lasting cognitive benefits, with potential applications for treating depression, PTSD, and neurodegenerative diseases. Both male and female mice benefited, and the study’s advanced testing system may accelerate future research into targeted psychedelic therapies.
Key Facts:
Long-Lasting Effects: One dose of 25CN-NBOH improved learning adaptability for 15–20 days.
One dose of 25CN-NBOH improved learning adaptability for 15–20 days. Brain Flexibility: Mice showed enhanced performance on reversal learning tasks.
Mice showed enhanced performance on reversal learning tasks. Broad Potential: Effects were observed in both sexes, with implications for treating cognitive disorders.
Source: Genomic Press
In a groundbreaking research study, University of Michigan researchers have discovered that a single dose of a psychedelic compound can enhance cognitive flexibility—the brain’s ability to adapt to changing circumstances—for weeks after administration, potentially revolutionizing treatments for depression, PTSD, and neurodegenerative diseases.
The study, published today in the journal Psychedelics, demonstrates that mice treated with a single dose of 25CN-NBOH, a selective serotonin 2A receptor agonist, showed markedly improved performance in reversal learning tasks compared to control groups when tested 2-3 weeks after treatment.
Importantly, the study found that both male and female mice showed significant improvements in cognitive flexibility, suggesting the potential broad applicability of psychedelic therapy across biological sexes. Credit: Neuroscience News
Key Findings
“What makes this discovery particularly significant is the sustained duration of cognitive benefits following just one psychedelic dose,” explains Professor Omar J. Ahmed, the study’s senior, corresponding author from the University of Michigan’s Department of Psychology.
“We observed enhanced learning adaptability that persisted for weeks, suggesting these compounds may induce lasting and behaviorally meaningful neuroplasticity changes in the prefrontal cortex.”
Using an innovative automated sequential learning paradigm, researchers measured how effectively mice could adapt to rule reversals—a standard test for cognitive flexibility.
The psychedelic-treated mice demonstrated superior adaptability compared to saline controls, with enhanced task efficiency, higher percentages of correct trials, and increased reward acquisition during the reversal phase.
Implications for Brain Science
The results complement existing cellular research showing psychedelic-induced structural remodeling in the prefrontal cortex but uniquely demonstrate sustained cognitive benefits persisting long after the immediate effects of the drug have dissipated.
As interest in psychedelic medicine continues to grow, this research raises intriguing questions about how psychedelics might reshape neural pathways governing flexible thinking.
Could these compounds potentially reopen critical periods of brain plasticity? What molecular mechanisms underlie these long-lasting cognitive improvements? How might the timing and frequency of administration affect long-term neuroplasticity?
“The current study focused on the long-term effects of a single psychedelic dose. A key question is what happens with two, three, or even twenty doses taken over several months.
“Is every additional dose increasingly beneficial for flexible learning or is there a plateau effect or even a negative effect of too many doses? These are important questions to answer next in the quest to make psychedelic medicine more rational and mechanistic,” according to Dr. Ahmed.
Sex Differences and Clinical Potential
Importantly, the study found that both male and female mice showed significant improvements in cognitive flexibility, suggesting the potential broad applicability of psychedelic therapy across biological sexes.
“The most striking aspect of our findings is that these cognitive benefits were measured 15-20 days after a single psychedelic administration,” notes Elizabeth J. Brouns, first author of the study.
“This suggests that a single dose of a psychedelic isn’t just temporarily altering perception, but potentially inducing lasting beneficial changes in brain function.”
Methodological Advances
The study’s automated behavioral task represents a significant methodological advance for evaluating flexible learning, enabling researchers to efficiently evaluate cognitive flexibility in future investigations of psychedelic compounds.
This high-throughput approach could accelerate the development of targeted psychedelic therapies for specific cognitive deficits.
About this psychopharmacology and neuroplasticity research news
Author: Ma-Li Wong
Source: Genomic Press
Contact: Ma-Li Wong – Genomic Press
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Single-dose psychedelic enhances cognitive flexibility and reversal learning in mice weeks after administration” by Omar J. Ahmed et al. Psychedelics
Abstract
Single-dose psychedelic enhances cognitive flexibility and reversal learning in mice weeks after administration
Psychedelic compounds have demonstrated remarkable therapeutic potential for treating neuropsychiatric disorders by promoting sustained neuroplasticity in the prefrontal cortex (PFC).
Cognitive flexibility—the ability to adapt previously learned rules to novel situations—represents a critical PFC function that is frequently impaired in depression, PTSD, and neurodegenerative conditions.
In this study, we demonstrate that a single administration of the selective serotonin 2A receptor agonist 25CN-NBOH produces significant, long-lasting improvements in cognitive flexibility in both male and female mice when measured 2–3 weeks posttreatment.
Using a novel automated sequential learning paradigm, psychedelic-treated mice showed superior adaptability in rule reversal tasks compared to saline controls, as evidenced by enhanced poke efficiency, higher percentages of correct trials, and increased reward acquisition.
These behavioral findings complement existing cellular research showing psychedelic-induced structural remodeling in the PFC and uniquely demonstrate sustained cognitive benefits persisting weeks after a single psychedelic dose.
Our automated behavioral task provides a high-throughput method for evaluating cognitive flexibility effects of various psychedelic compounds, offering important implications for therapeutic applications in conditions characterized by cognitive rigidity, including depression, PTSD, and potentially Alzheimer’s disease.
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