Researchers from the University of Michigan (UM) have found that a single dose of the psychedelic compound 25CN-NBOH significantly enhanced cognitive flexibility in mice for up to three weeks after administration. The findings, published in Psychedelics, suggest that this and other psychedelics may be used to promote long-lasting improvements in brain function, with potential therapeutic implications for conditions including depression, PTSD, and neurodegenerative diseases such as Alzheimer’s disease (AD).
“What makes this discovery particularly significant is the sustained duration of cognitive benefits following just one psychedelic dose,” said senior author Omar J. Ahmed, PhD, an assistant professor in 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.”
The compound tested, 25CN-NBOH, is a selective serotonin 2A (5-HT2A) receptor agonist known for its high affinity and specificity for this receptor subtype. The 5-HT2A receptor is widely considered central to the neurological effects of psychedelics and has previously been implicated in promoting synaptogenesis and structural remodeling in the prefrontal cortex (PFC). In this study, researchers evaluated its behavioral effects on flexible learning, a cognitive function regulated by the PFC.
Cognitive flexibility is the capacity to adapt to changing rules and environments. Its function is often impaired in psychiatric and neurological disorders. For their research, the investigators used a novel automated reversal learning task to measure how well mice could adjust to changes in learned rules. Mice were administered either a single dose of 25CN-NBOH or a saline control. After a two-week delay, both male and female mice that received the psychedelic showed significantly greater adaptability in the reversal phase of the task, as measured by poke efficiency, accuracy of trials, and number of rewards earned.
“The most striking aspect of our findings is that these cognitive benefits were measured 15–20 days after a single psychedelic administration,” said first author Elizabeth J. Brouns, a research assistant at UM. “This suggests that a single dose of a psychedelic isn’t just temporarily altering perception but potentially inducing lasting beneficial changes in brain function.”
Read the full article on Inside Precision Medicine.
