Psychedelic substances act on the brain by binding to serotonin receptors. Scientists have identified at least 14 different receptors that respond to the neurotransmitter serotonin. Psychedelics are especially drawn to one known as the 2A receptor. This receptor not only affects learning but also dampens activity in parts of the brain responsible for processing visual information.
“We have observed in earlier studies that visual processes in the brain are suppressed by this receptor,” says Callum White, first author of the study. “This means that visual information about things happening in the outside world becomes less accessible to our consciousness. To fill this gap in the puzzle, our brain inserts fragments from memory — it hallucinates.”
In other words, when incoming visual signals are reduced, the brain compensates by pulling stored images and experiences from memory. Those internally generated fragments can blend into perception, producing hallucinations.
Slow Brain Waves Shift Perception Toward Memory
The researchers also uncovered how this shift unfolds in real time. Psychedelics increase rhythmic patterns of brain activity, known as oscillations, in visual regions. Oscillations are coordinated waves of neural firing that help different parts of the brain communicate with each other.
After psychedelics were administered, the team observed a rise in low-frequency (5-Hz) waves in visual areas. These slower waves stimulated another region called the retrosplenial cortex, a key hub involved in accessing stored memories. As this communication strengthens, the brain enters a different operating mode. Awareness of current external events becomes weaker, while perception relies more heavily on recalled information. As Professor Dirk Jancke, who led the study, describes it, the experience is “a bit like partial dreaming.”
Real-Time Brain Imaging Reveals the Mechanism
To capture these changes, the scientists used an advanced optical imaging technique that tracks neural activity across the entire surface of the brain in real time. The experiments relied on specially engineered mice created by Professor Thomas Knöpfel at Hong Kong Baptist University. These animals were designed to produce fluorescent proteins in specific types of brain cells.
This approach allowed researchers to pinpoint the source of the signals they recorded. “We therefore know exactly in our experiments that the measured fluorescent signals originate from pyramidal cells of the cortical layers 2/3 and 5, which mediate communication within and between brain regions,” says Jancke. These cells play a central role in transmitting information across the cortex.
Implications for Depression and Anxiety Treatment
The findings may also help refine psychedelic-assisted therapy. Researchers believe that, under medical supervision, these substances can temporarily shift brain activity in ways that encourage the recall of positive memories and weaken deeply ingrained negative thought patterns.
“When used under medical supervision, such substances can temporarily change the state of the brain to selectively recall positive memory content and restructure learned, excessively negative thought patterns, i.e., to be able to unlearn negative context. It will be exciting to see how such therapies are further personalized in the future,” says Jancke.
By clarifying how psychedelics redirect perception from the outside world to internal memory networks, the study provides a clearer biological explanation for both hallucinations and the growing therapeutic potential of these compounds.
