A single dose of a psychedelic compound can enhance the brain’s ability to adapt to changing circumstances for weeks after administration, potentially paving the way for new treatments for depression, PTSD, and neurodegenerative diseases.
A recent study demonstrates that mice treated with a single dose of 25CN-NBOH, a seletive serotonin 2A receptor agonist, showed markedly improved performance in reversal learning tasks compared to control groups when tested two-three weeks after treatment.
Professor Omar J. Ahmed is the study’s senior, corresponding author from the University of Michigan’s Department of Psychology.
The researcher said: “What makes this discovery particularly significant is the sustained duration of cognitive benefits following just one psychedelic dose.
“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.
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.
Dr Ahmed said: “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.”
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.
Elizabeth J. Brouns, first author of the study, said: “The most striking aspect of our findings is that these cognitive benefits were measured 15-20 days after a single psychedelic administration.
“This suggests that a single dose of a psychedelic isn’t just temporarily altering perception, but potentially inducing lasting beneficial changes in brain function.”
