Participants took 25mg of psilocybin, reporting deeper psychological insight and better wellbeing a month later
Scientists spotted apparent changes in the brain’s structure which were still apparent a month after healthy volunteers took the drug. If confirmed, they may help explain the therapeutic effects that psychedelics can have on anxiety, depression and addiction, researchers said.
Evidence for the changes came from specialised scans that measured the diffusion of water along nerve bundles in the brain. They suggested that some nerve tracts had become denser and more robust after the drug was taken. While the findings are preliminary, the scientists said the opposite was seen in ageing and dementia.
“It’s remarkable to see potential anatomical brain changes one month after a single dose of any drug,” said Prof Robin Carhart-Harris, a neurologist at the University of California, San Francisco, and senior author on the study. “We don’t yet know what these changes mean, but we do note that overall, people showed positive psychological changes in this study, including improved wellbeing and mental flexibility.”
Scientists have long sought to understand how psychedelics affect the brain and the work has gained fresh impetus in the wake of trials and studies that suggest the compounds could be used to treat a range of mental health disorders. The drugs are thought to help by boosting flexible thinking and allowing people to escape destructive cognitive ruts.In the latest study, Carhart-Harris and colleagues at Imperial College London explored the “entropic brain effect”, in which neural activity becomes more varied on psychedelics; the impact of the drug on people’s wellbeing alongside any functional or anatomical changes in the brain.
To start, 28 healthy volunteers who had never taken a psychedelic were given 1mg of psilocybin, a small enough dose to be considered a placebo. The scientists then used electroencephalography (EEG) to measure their brain activity via electrodes on the scalp.
The volunteers completed a raft of tests over the next few weeks to measure their wellbeing, depth of psychological insight and the flexibility of their thinking. Meanwhile, functional MRI scans and a technique called diffusion tensor imaging (DTI) monitored their brains.
A month after the placebo, participants took a single 25mg dose of psilocybin, enough to elicit a powerful psychedelic experience. During the trip and for weeks after, the scientists ran the same tests and brain monitoring to see what happened.
Within an hour of taking the drug, EEG revealed a surge in brain entropy, suggesting the brain was processing a greater diversity of information. A month later, DTI scans revealed a drop in diffusion along nerve tracts running from the front to the middle of the brain. That could be caused by pruning of some nerve fibres, or the growth of nerves that are not yet covered with insulating sheaths, though more work is needed to confirm the finding.
Writing in Nature Communications, the researchers describe another key finding. Those who had the largest spike in brain entropy after psilocybin were most likely to report deeper psychological insight and better wellbeing a month later, underlining the link between flexible thinking and improved mental health. “It suggests a psychobiological therapeutic action for psilocybin,” said Carhart-Harris.
Prof Alex Kwan, a neuroscientist at Cornell University in New York, said studies in mice had shown that psychedelics can rewire connections between nerves, a form of “plasticity” that could underlie their therapeutic effects. The big question is whether the same occurs in humans. “This study comes closer than most to addressing that question, by giving evidence of lasting changes in brain structure after psychedelic use,” he said. But while the results were “exciting”, the study involved a small number of people and DTI provides an indirect and limited view of brain connections, he said.
Summary: For years, scientists have focused on how psychedelics “rewire” neurons. But a groundbreaking study has found a “missing link” in long-term PTSD recovery: myelin remodeling. Researchers discovered that psilocybin and MDMA do more than just alter brain activity; they trigger the physical repair of myelin—the insulating layer that protects nerve fibers and synchronizes brain signals.
By “re-insulating” the circuits that have been frayed by trauma, these drugs help harmonize the rhythm of brain networks, turning a temporary “psychedelic window” into a permanent structural recovery.
Key Facts
Source: Elsevier
Post-traumatic stress disorder (PTSD) is not only characterized by strongly encoded traumatic memories, but also by disrupted coordination across brain networks.
New research shows that treatment with psychedelic drugs triggers a large-scale reconfiguration of brain network dynamics driven by the remodeling of myelin—the neuronal insulation layer.
The findings from the novel study in Biological Psychiatry show enhancing myelination might be a viable strategy to augment or sustain the therapeutic effects of psychedelic-assisted treatments for PTSD and related disorders.
Psilocybin and 3,4-methylenedioxymethamphetamine (MDMA) produce rapid clinical effects in patients with PTSD. However, durable benefits require circuit-level stabilization.
As the underlying cellular mechanisms remain incompletely understood, the current study identifies myelin as the missing link bridging the short-lived psychedelic experience and longer-term maintenance of healthier neural network dynamics.
The study shows that activity-dependent oligodendrogenesis and myelin remodeling can tune the disrupted timing and persistent response to threat observed in PTSD by synchronizing and harmonizing the rhythm of brain circuits.
John Krystal, MD, Editor of Biological Psychiatry, explains, “The focus of psychedelic and MDMA research has been the effects of these drugs on neurons and neuroplasticity. This work has largely ignored a potentially important role for other cell types in the neurobiology of their therapeutic effects.
“Oligodendrocytes play a number of roles in the brain, which produce the myelin that insulates neurons. Subgroups of oligodendrocytes take up glutamate and contribute to glutamate homeostasis, protecting the brain from neurotoxicity. Another group of oligodendrocytes is involved in immune and inflammatory functions in the brain.”
Researchers used a rat model of contextual fear conditioning and administered repeated low doses of psilocybin or MDMA. They then quantified anxiety-like and exploration behaviors and assessed spatial learning and memory.
The results showed that anxiety-like behaviors were reduced—a shift accompanied by changes in oligodendrocyte biology and multi-omic (genetic) signatures towards myelin remodeling in the dentate gyrus (part of the hippocampus, the brain’s memory center).
“To test whether myelin integrity was simply associated with behavioral change—or actually required for it—we combined the drug interventions with models that either damaged brain insulation (demyelination) or chemically enhanced it (promyelination) to see how these changes affected recovery,” explains lead investigator Mehmet Bostancıklıoğlu, PhD, Department of Physiology, Gaziantep University Faculty of Medicine, Gaziantep, Turkey.
Using high-powered microscopy and genetic analysis, the researchers confirmed both psilocybin and MDMA trigger physical myelin repair. Furthermore, a serotonin receptor 5-HT2A blockade prevented both the behavioral and myelin-associated effects.
When the team used a different drug (anisomycin) to block the formation of fear memories, anxiety decreased, but the myelin remained unrepaired. This suggests that while memories can be suppressed, biological recovery requires the structural support of myelin.
“Taken together, this moves oligodendrocytes and adaptive myelination from ‘background correlates’ to a mechanistically testable gate on the durability of psychedelic-associated circuit change,” notes Dr. Bostancıklıoğlu.
“The implication of oligodendrocytes in the therapeutic effects of psychedelics and MDMA is important because of their many functions in the brain, including myelin formation, glutamate homeostasis, and neuroinflammation. The dependency of the therapeutic effects of these drugs in animals may suggest that myelin compromise may undermine their efficacy,” adds Dr. Krystal.
“Overall, these data suggest that psychedelics and MDMA, like selective serotonin reuptake inhibitors (SSRIs) and ketamine, may promote the recovery from stress-related damage to myelin, contributing to clinical recovery.”
The study also found that psilocybin and MDMA reduce astrocyte reactivity that can cause inflammation.
The investigators point out that enhancing myelination would not be expected to replace psychotherapy; rather, it could support consolidation and maintenance of healthier network communication after the acute psychedelic session, when the brain is transitioning from destabilization back towards reintegration.
Dr. Bostancıklıoğlu concludes, “We often talk about psychedelics as ‘opening a window’ for brain plasticity. Recent work emphasizes that these drugs can acutely loosen entrenched network patterns and then leave a sub-acute period in which experience can reshape circuits.
“What we show here is that myelin-producing cells may be an underappreciated part of that story—helping translate a transient window into longer-lasting circuit change, at least in a fear-based rat model.”
A: No—this study shows they actually help fix the wiring. Trauma “frays” the insulation (myelin) of your brain’s communication lines, leading to static and mistimed signals. Psychedelics like psilocybin and MDMA trigger the brain to physically re-wrap those wires, allowing for clearer, calmer communication.
A: In PTSD, the brain’s fear circuits are often “over-active” and poorly timed. Myelin ensures that signals travel at the right speed. By repairing this insulation, the brain can better synchronize its networks, helping to “turn down the volume” on persistent threat responses.
A: Not quite. The researchers emphasize that these drugs “open a window” of plasticity. The physical repair of myelin provides the structural support needed for that window to stay open, but it works best alongside therapy to reintegrate those healthier network patterns.
Author: Eileen Leahy
Source: Elsevier
Contact: Eileen Leahy – Elsevier
Image: The image is credited to Neuroscience News
Original Research: Open access.
“MDMA and Psilocybin Regulate Oligodendrocyte-Lineage Cell Numbers and Anxiety-Like Behaviors in a Rat Model of Fear” by Mehmet Bostancıklıoğlu, Davut Sinan Kaplan, Ramazan Bal, Elif Yiğit, Hasan Ulusal, and Ebru Temiz. Biological Psychiatry
DOI:10.1016/j.biopsych.2026.01.016
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