Ketamine may work by 'flattening the brain's hierarchies,' brain scans suggest
When you buy through links on our articles, Future and its syndication partners may earn a commission.
DENVER—A single dose of ketamine may subtly reshape how different regions of the brain communicate, a new study suggests.
The research, presented June 19 at the Psychedelic Science 2025 conference, is one of the first to investigate ketamine's impact on neuroplasticity — the ability to adapt to experiences by forming new connections and pathways — in the brains of living people. The findings have not been peer-reviewed yet.
In recent years, clinical trials have demonstrated ketamine's effectiveness in treating depression within a few hours of a single dose. Animal studies suggest that ketamine almost immediately spurs the growth of new dendritic spines — tiny protrusions that form synapses, the connections between brain cells. But it's been hard to pin down how ketamine works in living humans.
To answer that question, the researchers scanned the brains of 11 men using multiple techniques and then administered an intravenous dose of ketamine. One group of the people was re-scanned 24 hours after getting the single dose of the drug, and the other group was scanned again seven days later.
Related: 1 psychedelic psilocybin dose eases depression for years, study reveals
Normally, the brain processes sensory information via lower-level networks and then feeds that "up the chain" to higher-level networks that orchestrate larger brain processes. Higher level networks also send feedback to lower-order networks, but communication between high and low level networks is less than that within specific networks.
In the new study, scientists used functional magnetic resonance imaging (fMRI), which measures blood flow to different brain regions, to reveal how brain activity changed after treatment. When fMRI activity levels appear synchronized, it can imply the distinct areas are "communicating" with one another. Typically, regions that are part of a network consistently fire together when the brain is performing specific tasks or is in a certain mental state.
After the participants took ketamine, however, activity in specific networks seemed to be desynchronized. The researchers also found an increase in communication between a higher-order network, the default mode network (DMN), and lower-order, sensory networks, such as the somatomotor network, which is linked to the perception of the physical self and bodily sensations. This means that brain regions usually involved in basic sensory processing started communicating more directly and extensively with higher-level regions responsible for complex thought and "orchestrating" brain processes.
"Usually there is more segregation between these higher order and lower order networks," Claudio Agnorelli, a neuroscientist at the Centre for Psychedelic Research at Imperial College London, told Live Science. "But after the ketamine, this hierarchy is kind of collapsed."
The DMN is responsible for "mental time travel," or planning and daydreaming, rather than staying focused on particular tasks in the present. An overactive DMN has been linked to depression and rumination.
The researchers also used positron emission tomography (PET) scans to measure levels of a protein called SV2A, which plays a role in the release of brain signaling molecules. Higher SV2A levels are thought to indicate more connections between brain cells, Agnorelli said.
Although the researchers didn't identify a clear trend in global SVA2 levels after ketamine administration, one brain region tied to the DMN did show clear changes: the posterior cingulate cortex (PCC). The PCC is part of the DMN, and it seems to orchestrate the flow of information in the brain. After ketamine administration, the PCC played a smaller role in orchestrating communication across the brain, even as synaptic connections increased within the PCC.
RELATED STORIES
—FDA approves ketamine-like nasal spray for depression — here's everything you need to know
—'Hyper-synchronized' brain waves may explain why different psychedelics have similar effects, rat study reveals
—How does ketamine work as an antidepressant? It's complicated.
The finding of increased synaptic density in the DMN suggests ketamine isn't just creating new synapses — it's fundamentally reorganizing how brain networks communicate, Sam Mandel, CEO and co-founder of Ketamine Clinics Los Angeles, told Live Science in an email. "The 'flattening of cortical hierarchy' could explain why patients often report feeling less trapped in rigid thought patterns after treatment."
The authors cautioned that their results are preliminary. The study had just 11 participants, all of whom were men with no underlying conditions, and there was no placebo group for comparison. Moreover, the imaging methods the team used are still being validated as reliable markers of brain changes. The study does, however, help bridge the gap between what is known about ketamine's impact on animals and how it may act in humans, Agnorelli said.
"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 new development," Mandel said.
Hashtags
Try Our AI Features
Explore what Daily8 AI can do for you:
Comments
No comments yet...
Related Articles
Medscape
12 minutes ago
- Medscape
Key Abstracts in Early-Stage NSCLC From ASCO 2025
Dr Jonathan Goldman of the University of California, Los Angeles, highlights key abstracts in early-stage NSCLC from ASCO 2025. Dr Goldman begins with updated results from CheckMate 816, comparing neoadjuvant chemotherapy (chemo) vs chemo + nivolumab. Median overall survival (OS) in the nivolumab arm remains unreached vs 73.7 months with chemo alone. Event-free survival (EFS) is durable at 59.6 vs 21.1 months, as evidenced by 5-year EFS of 49% in the combination arm. Next, he reviews the NeoADAURA trial evaluating neoadjuvant osimertinib ± chemo in resectable EGFR-mutated stage II-IIIB NSCLC. Major pathologic response was higher in osimertinib-containing arms (26% and 25%) vs 2% in the chemo arm, although long-term outcomes remain pending. Dr Goldman also discusses the SWOG/NRG S1914 trial of perioperative stereotactic body radiotherapy ± atezolizumab, which did not show improvements in OS or progression-free survival (PFS). He then highlights a prospective, low-dose CT screening study of the Mississippi Delta cohort, which showed a 4.7% lung cancer detection rate overall and 4.5% in patients with incidental pulmonary nodules — underscoring the utility of low-dose CT as a modality in early detection. In closing, he reports on two studies in small cell lung cancer. The IMforte study showed that lurbinectedin + atezolizumab in 1L maintenance improved PFS (HR, 0.54). In the DeLLphi-304 study, second-line tarlatamab improved OS compared to chemo (HR, 0.6), which is a potentially practice-changing update.
Wall Street Journal
16 minutes ago
- Wall Street Journal
Health Insurers to Promise Changes to Preapproval Process That Drew Backlash
Following the backlash that hit health insurers after the killing of a top executive last year, the industry will pledge steps meant to smooth the controversial preapproval process that can deny or delay access to care. The initiative is set to be unveiled early next week, according to people familiar with the matter.
CBS News
22 minutes ago
- CBS News
Chicago officials detail preparation efforts, offer tips ahead of this weekend's extreme heat
With the extreme heat approaching, pools and waterparks will be busy, but according to city officials, taking a dip will not be the only precaution people will need this weekend. Scorching temperatures and high humidity are a bad combo, especially when that's the forecast for three days in a row, making heat stroke a real possibility. On Friday, city officials, including Mayor Brandon Johnson and the Office of Emergency Management and Communications, discussed the measures they're taking ahead of and during the first heat wave of the year. The city said it plans to operate cooling centers, but beware that many of them are only open on weekdays. In that case, libraries, park district buildings, and police stations are some spots where people can find some relief over the weekend. Officials also shared some alarming numbers showing how dangerous a heat wave can be. "Over the last three years, we have recorded 485 heat-related deaths in Chicago and more than 700 heat-related emergency department visits," Chicago Department of Public Health Commissioner Dr. Olusimbo Ige said. She added that men are more likely to experience a heat-related emergency than women. OEMC executive director Francisco Velez said they are monitoring the heat closely. "OEMC is working directly with the National Weather Center 24/7 to monitor the weather events and will alert residents if conditions worsen. OEMC is coordinating with city departments and sister agencies to ensure services and resources are available in response to the heat," he said. Mayor Johnson also stressed the importance of staying informed and checking on those with health conditions. "Over the next few days, make sure that we check in on our loved ones and neighbors, especially our seniors and those with health conditions, individuals with disabilities. We do have cooling locations all over the city, we have street outreach workers who are available as well to connect the unhoused Chicagoans with those resources," Johnson said. Doctors said seniors and anyone who takes beta blockers, diuretics, and sedatives are the most at risk. If you are worried about someone who lives in Chicago and can't make contact with them, you're encouraged to call 311 and request a well-being check.
