A single dose of a psychedelic compound can boost cognitive flexibility for weeks after treatment, according to research from the University of Michigan. The discovery could transform how we treat conditions ranging from depression to neurodegenerative diseases.
The study, published April 22 in the journal Psychedelics, found that mice given just one dose of a serotonin receptor activator called 25CN-NBOH performed significantly better on learning tasks 2-3 weeks later compared to untreated mice.
“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 author. “We observed enhanced learning adaptability that persisted for weeks, suggesting these compounds may induce lasting and behaviorally meaningful neuroplasticity changes in the prefrontal cortex.”
The research team measured cognitive flexibility—the brain’s ability to adapt to changing circumstances—using a specialized learning test where mice had to adjust to reversed rules. Treated mice showed remarkable improvement in handling these mental shifts long after the drug’s immediate effects had worn off.
This finding is particularly exciting because cognitive flexibility is crucial for mental health. Many psychiatric conditions, including depression and PTSD, involve rigid thinking patterns that can be difficult to change with traditional therapies.
“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.”
Unlike many psychedelic studies focused on immediate experiential effects, this research demonstrates lasting improvements in actual cognitive performance—suggesting these compounds might fundamentally rewire neural pathways governing flexible thinking.
Another significant finding was that both male and female mice showed improvements, indicating potential broad applicability across biological sexes—an important consideration for future human treatments.
Dr. Ahmed raises intriguing questions about the future of this research: “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?”
The study’s innovative automated testing methods also represent a breakthrough, potentially accelerating how researchers can evaluate cognitive effects of various compounds in the rapidly expanding field of psychedelic medicine.
As scientists continue to unravel the neurobiological mechanisms behind these lasting cognitive benefits, the research raises tantalizing possibilities about reopening periods of brain plasticity—potentially offering new hope for conditions where cognitive flexibility is impaired.
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