Study Suggests Ketamine Alters Brain Communication
DENVER—A recent study indicates that a single dose of ketamine might subtly change how different parts of the brain interact with each other.
This research, shared on June 19 at the Psychedelic Science 2025 conference, is among the first to explore ketamine’s effect on neuroplasticity—the brain’s ability to adapt by forming new connections—in living humans. It’s worth noting that these findings have yet to undergo peer review.
In the last few years, clinical trials have shown ketamine can effectively treat depression within hours. Animal studies have suggested that ketamine quickly encourages the growth of new dendritic spines, which are small protrusions that create synapses, the connections between brain cells. However, understanding how this works in humans has proven challenging.
To delve into this, researchers scanned the brains of 11 men using various techniques before they received an intravenous dose of ketamine. One group was scanned 24 hours after treatment, while another group was scanned again a week later.
Typically, the brain processes sensory information through lower-level networks, which then send that information “up the chain” to higher-level networks for more complex processing. Communication between these higher and lower networks tends to be less frequent compared to interactions within specific networks.
After ketamine administration, however, the activity in particular networks appeared to be less synchronized. Interestingly, the researchers noted that communication increased between a higher-order network, known as the default mode network (DMN), and lower-order sensory networks. This change suggests that brain areas usually tied to basic sensory processing began to communicate more directly with regions responsible for complex thought.
“There is typically more segregation between higher and lower order networks,” explained Claudio Agnorelli, a neuroscientist from the Centre for Psychedelic Research at Imperial College London. “But after taking ketamine, that hierarchy sort of collapses.”
The DMN is essential for activities like planning and daydreaming, which means it’s not always focused on present tasks. When it becomes overly active, it’s linked to issues such as depression and rumination.
The researchers also employed positron emission tomography (PET) scans to assess levels of a protein called SV2A, implicated in the release of brain signaling molecules. Higher levels of SV2A may indicate greater connectivity between brain cells, according to Agnorelli.
Although no clear trend emerged in global SV2A levels post-ketamine treatment, one specific brain area connected to the DMN—the posterior cingulate cortex (PCC)—did show significant changes. The PCC, part of the DMN, generally plays a role in managing information flow, but its influence appeared to diminish after ketamine use, even as connections within the PCC increased.
The increased density of synapses in the DMN suggests that ketamine is not just fostering new connections but is also reorganizing the communication patterns of brain networks. Sam Mandel, CEO of Ketamine Clinics Los Angeles, noted that this “flattening of cortical hierarchy” might explain why patients often feel less constrained by rigid thought patterns post-treatment.
However, the authors emphasized that these results are preliminary. The study involved only 11 men with no underlying issues and lacked a placebo group for comparison. Additionally, the imaging methods used are still being validated. Nonetheless, this research helps to bridge the knowledge gap regarding ketamine’s effects seen in animals and its potential implications for humans, Agnorelli remarked.
“While we’ve long understood from animal studies that ketamine promotes neuroplasticity, actually visualizing these synaptic changes in living human brains using a PET tracer is a notable advancement,” Mandel added.
