Psilocybin appears to alter how the brain integrates tactile sensory inputs

A new double-blind, placebo-controlled neuroimaging study sheds light on how psilocybin alters the way in which the brain processes tactile sensations and mental representations of one’s body. The findings have been published in Cerebral Cortex.

Psilocybin, the active component in so-called “magic” mushrooms, exerts its psychological effects primarily via the serotonin 2A receptor (5-HT2A) and is known to cause alterations in self/body boundaries. But much remains to be learned about the neurocognitive processes underlying these changes in perception.

“Psilocybin and other psychedelic substances are increasingly being tested as therapeutic agents for mental illnesses. However, the clinical mechanism of action is currently unclear,” said study author Katrin Preller (@KatrinPreller) of the University of Zurich.

“Furthermore, a lot of patients suffering from psychiatric disorders experience alterations in how they perceive their bodily self. Yet, it is currently unclear how the brain produces these alterations in bodily self-perception. As psilocybin induces temporary changes in bodily self-perception, administration of psilocybin allowed us to study the underlying neurobiological mechanisms.”

The study was based on predictive coding theory, which describes perception as a process of hypothesis testing. According to the theory, the brain constructs a model of reality to predict incoming sensory input and updates the model whenever an unexpected stimulus is encountered.

“The sense of touch is not raw and direct but rather constructed with reference to internal body representations that contain prior expectations,” the researchers explained in their study.

When the brain receives an unexpected sensory input, it generates a particular electrical wave called mismatch negativity. To examine this brain response, the participants completed a somatosensory oddball task under the influence of psilocybin and a placebo. In the task, a repetitive stream of electrical impulses was delivered to the left forearm, but the standard stream was sometimes interrupted by a deviant pattern of electrical impulses.

During the task, Preller and her colleagues recorded blood oxygenation levels in the brain using functional magnetic resonance imaging (fMRI) and recorded electrical brain activity using electroencephalography (EEG).

The researchers observed less divergence in how the brain responded to the standard and deviant stimuli when participants were under the effects of psilocybin. Psilocybin, compared to placebo, was associated with decreases in brain activity in response to surprising tactile stimuli versus habituated stimuli in the ventromedial prefrontal cortex, dorsomedial prefrontal cortex, primary visual cortex, and the cerebellum.

Psilocybin also reduced mismatch negativity EEG responses, and these alterations in brain activity were associated with self-reported experiences of unity and disembodiment.

“This study provides the first evidence that psilocybin alters the integration of tactile sensory inputs through aberrant prediction error processing and highlights the importance of the 5-HT2A system in tactile deviancy processing as well as in the integration of bodily and self-related stimuli. It is therefore conceivable that the serotonin 2A receptor system may be involved in disorders characterized by changes in bodily self-processing,” Preller told PsyPost.

The findings are similar to the results of another study, which examined how the psychedelic drug LSD influenced brain responses during an auditory oddball task.

But the new study only included 15 participants. “Larger studies need to replicate these results,” Preller said. “Furthermore, we need to test whether the mechanisms observed in this study with a tactile paradigm also translate to other sensory modalities.”

The study, “Psilocybin Induces Aberrant Prediction Error Processing of Tactile Mismatch Responses—A Simultaneous EEG–FMRI Study,” was authored by Patricia Duerler, Silvia Brem, Gorka Fraga-González, Tiffany Neef, Micah Allen, Peter Zeidman, Philipp Stämpfli, Franz X. Vollenweider, and Katrin H. Preller.