One Dose of Psychedelic Boosts Brain Flexibility for Weeks, Study Finds

In a recent study, scientists found that mice given just one dose of a psychedelic drug called 25CN-NBOH, which specifically targets serotonin 2A receptors (just like psilocybin!), showed major improvements in cognitive flexibility. That’s the brain’s ability to adapt and switch gears when things change, something that’s often impaired in conditions like depresia, PTSD, and neurodegeneratívne ochorenia.

One Dose of Psychedelic Boosts Brain Flexibility for Weeks, Study Finds

Published in the journal Psychedelics, the study, titled “Single-dose psychedelic enhances cognitive flexibility and reversal learning in mice weeks after administration,” showed that two to three weeks after a single dose, these mice outperformed untreated mice in tasks designed to measure learning adaptability. Basically, the mice who’d been given a psychedelic were smarter, quicker, and more mentally flexible.

The Psychedelic Caused Lasting Positive Changes

“What makes this discovery particularly significant is the sustained duration of cognitive benefits following just one psychedelic dose,” said Professor Omar J. Ahmed, the senior and 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,” vysvetlil.

How They Tested It

Researchers set up a clever experiment using an automated system. In one task (called the SEQFR2-forward protocol), mice had to poke a left button and then a right button within 30 seconds to earn a treat. Later, the rules flipped (in the SEQFR2-reversal protocol) — now they had to poke right first, then left.

This reversal is a classic test of cognitive flexibility, and the psychedelic-treated mice crushed it: they adapted to the rule change much better than the control group. They completed tasks more efficiently, made more correct moves, and snagged more reward pellets during the tricky reversal phase.

What This Means for Brain Science

This study is exciting because it adds to earlier cellular research showing that psychedelics can physically reshape parts of the brain like the prefrontal cortex. But here’s the new twist: this isn’t just a short-term boost. The benefits lingered long after the “high” was gone.

As the buzz around psychedelic medicine grows, this raises some big questions. Could psychedelics like psilocybin help reopen “critical periods” of brain plasticity — the windows when learning and adaptability are at their peak? What are the exact molecular changes making this happen? And how does the timing or number of doses change the long-term effects?

“The current study focused on the long-term effects of a single psychedelic dose,” said Dr. Ahmed.

“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.”

The Results Were the Same for Both Males and Females

One more interesting thing: the study found that both male and female mice showed big improvements, suggesting that psychedelic treatments could potentially work across sexes.

“The most striking aspect of our findings is that these cognitive benefits were measured 15–20 days after a single psychedelic administration,” said Elizabeth J. Brouns, the study’s first author.

“This suggests that a single dose of a psychedelic isn’t just temporarily altering perception, but potentially inducing lasting beneficial changes in brain function.”

Another cool piece: the team’s automated behavioral task could be a game-changer for future research. It makes it way easier (and faster) to evaluate how different compounds affect flexible thinking, hopefully speeding up the development of targeted psychedelic therapies for various cognitive challenges.

Get Inspired and Learn Something New?

Sure, you may not be a mouse, but why not try out a new skill, or practice something new, post-shroom-výlet or as part of a rutina mikrodávkovania? By helping our brains out of their well-worn ruts we become more adaptable, more open — in a way, our brains can become ‘young’ again.