Brain responses to predictable images differ in people who recently used psychedelics

The question

Do serotonergic psychedelics loosen the brain’s reliance on its own predictions in the days and weeks after a single dose? The researchers tested this idea directly in people and in mice.

What they did

People who had used a psychedelic that acts on the 5-HT2A serotonin receptor (psilocybin or LSD) within the past three weeks were compared with non-users matched for age and sex. Both groups did a task involving predictable eye movements to visual targets while brain activity was recorded with EEG (electrodes on the scalp) and eye movements were tracked. A second group of people who had used 5-MeO-DMT was tested the same way. In parallel, mice were given psilocybin (1 mg/kg) and recordings were made directly from the visual cortex 24 hours later.

What they found

Compared with non-users, recent psychedelic users made fewer fast eye movements and showed less dampening of slow (delta and theta) brain waves when a visual stimulus was predictable. The size of these differences was related to how much time had passed since the person’s psychedelic use. The same pattern appeared in the separate group who had used 5-MeO-DMT. In mice, psilocybin produced a similar loss of predictive dampening in the visual cortex 24 hours after dosing, along with weaker top-down signalling from a prefrontal region and growth of new connection points on the prefrontal neurons that feed into visual cortex.

The fine print

The human part was not a trial: people chose to use psychedelics on their own, so differences in personality, lifestyle or other drug use could explain the results rather than the psychedelic itself. The abstract does not report how many people took part, what doses they used, or how their use was verified, and no mental health outcomes were measured. Much of the mechanistic evidence comes from mice, which may not translate to people. This is a preprint that has not yet been peer reviewed, and this summary is based on the abstract only.

What it means

The study offers early, indirect support for the idea that psychedelics temporarily loosen the brain’s top-down predictions about incoming information, but it does not show that this change helps any mental health condition.

Evidence grade: Very low. Observational comparison of self-selected recent psychedelic users with matched non-users, with no participant numbers reported, published as a preprint that has not been peer reviewed.

This summary is based on the study’s published abstract.