In brief
- A team from the Allen Institute and the University of California recorded 46,360 neuronal units in 35 mice across control and psilocybin-containing conditions.
- The substance barely alters the total firing rate of neurons; what changes is the pattern—the bursts with which they fire.
- Blocking the 5-HT2A receptor eliminates many of these changes, but not all, suggesting other pathways are also involved.
A paper published on August 19 as a preprint on bioRxiv offers one of the most detailed maps to date of what psilocybin does inside the brain while its effects are active. The authors combined state-of-the-art electrodes with electroencephalography to track, almost neuron by neuron, how the conversation between brain regions changes following a dose.
An unusually large-scale recording
The team implanted Neuropixels probes, capable of capturing the activity of thousands of neurons simultaneously, into the cortex, thalamus, hippocampus, and striatum of 35 mice. The 47 sessions and 46,360 units include 22 psilocybin, 17 saline and 8 ketanserin-plus-psilocybin sessions; not every unit was recorded under psilocybin. A portion of the animals was also administered ketanserin, a 5-HT2A/5-HT2C antagonist, limiting selective attribution; 5-HT2A is a target shared by classic psychedelics like psilocybin—to distinguish which effects depend on that receptor and which do not. Scale matters: almost everything we know about the brain under the influence of psychedelics comes from studies focused on a specific region, rather than the whole.
Bursts, not volume
The surprise was not in how much the neurons fired, which barely varied in global terms, but in how they did it. In the reticular nucleus of the thalamus and the anterior thalamus, firing bursts clearly increased—a pattern that ketanserin completely abolished. In the hippocampus, within the CA1 and CA3 zones, the opposite occurred: the proportion of neurons firing in bursts dropped significantly, and this effect also disappeared when the receptor was blocked. However, some changes in the cortex and the electroencephalographic recording persisted even with ketanserin, indicating that not everything is mediated by the 5-HT2A receptor. The authors point to the reticular nucleus of the thalamus, a kind of filter that decides which sensory information reaches the cortex, as one of the points most sensitive to the substance.
What it implies
It is important to place this finding in context. It is a preprint, still without peer review, conducted in mice with acute dosing and an analysis window extending to 60 minutes after the second injection, so it does not provide direct evidence regarding therapeutic efficacy in humans. What it does provide is a piece of a larger puzzle: why an experience lasting a few hours is accompanied, in some cases, by mood changes that last for weeks remains largely a mechanistic mystery. Separating what depends on the 5-HT2A receptor from what does not is a necessary step for those attempting to design molecules with similar benefits but without the “trip,” a line of research that is already attracting investment within psychedelic-assisted therapy research. For now, the most honest data point is this: under psilocybin, the brain appears to change the way regions communicate more than the raw volume of that communication.
Source
- Momi D, Nahas Y, Wyrick D, et al. Brain-wide reconfiguration of burst firing by psilocybin reveals 5-HT2A-dependent circuit dynamics. bioRxiv (preprint, not peer-reviewed), August 19, 2026.
Educational content written from a harm reduction perspective and with respect for individual freedom. It is not a substitute for advice from a healthcare professional and is not intended to encourage or condemn any drug use.
