The room dissolves into a rushing collage of childhood bedrooms, long-forgotten faces and the exact shade of blue from an old family car. For many people who take psilocybin, these memory-fueled visions feel less like imagination and more like being dropped back into their own past. In 2024, a Nature study that scanned 18 participants over 8 sessions offered the clearest view yet of what might be happening inside the brain during and after those journeys, suggesting that psychedelics temporarily rewire core networks. I want to unpack what that rewiring looks like, why it could matter for therapy and where the science still falls short.
The Entropic Brain Theory
One influential attempt to explain psychedelic visions comes from Robin Carhart-Harris and Karl Friston, who merged the entropic brain hypothesis with predictive processing and the free-energy principle. In their synthesis, they argue that psychedelics relax high-level “priors” in the brain and increase bottom-up information flow from regions such as the limbic system and hippocampus, effectively letting raw emotional and memory signals flood higher-order networks. In their words, brain activity under psychedelics shows increased entropy, meaning neural signals become more variable and less constrained, which they link to the fluid, dreamlike quality of the psychedelic state described in their authoritative framework.
According to this account, when priors lose their grip, the brain’s usual predictive filters loosen and previously suppressed content can surface into consciousness. That makes it a compelling model for how personal memories might drive the intense imagery and autobiographical scenes many people report. At the same time, Carhart-Harris and Friston acknowledge that higher entropy and relaxed priors do not automatically translate into a one-to-one map of specific visions, so any direct causal link between the theory and particular images remains uncertain. Their work instead offers a mechanistic backdrop for why memory-laden material may have such an easy route into awareness under psilocybin.
Key Evidence from Psilocybin Trials
The most detailed human evidence for network “rewiring” under psilocybin comes from a longitudinal precision fMRI study published in Nature. In that randomized crossover trial with an active methylphenidate control, researchers scanned 18 participants across 8 sessions, building high-resolution maps of each person’s resting-state networks. During acute psilocybin sessions, they saw functional networks lose their usual boundaries: within-network correlations dropped while between-network anticorrelations weakened, with the default mode network, or DMN, showing the strongest desynchronization.
Reporting on the same work for a general audience, a high-quality explainer described this as a temporary “reset” of brain network patterns that persisted in subtler form for up to three weeks after the drug had worn off. The primary data indicated that within-network coherence in systems like the DMN fell by roughly 20 to 30 percent during the acute state, and some of that reorganization remained detectable weeks later. A separate research highlight emphasized that the study’s many repeated scans per subject were key to detecting both the short-term network dissolution and the lingering reconfiguration, framing the work as a milestone in precision functional mapping of psychedelic effects.
Memory’s Role in Psychedelic Visions
If networks are loosening, the next question is what content flows through the gaps. One primary fMRI study of psilocybin in 15 healthy subjects found that the psychedelic state increased BOLD signal variability across the brain, with pronounced peaks in the hippocampi and anterior cingulate cortex. The authors reported that psilocybin expanded the repertoire of dynamic connectivity states the brain explored, suggesting a more flexible, exploratory mode of operation in which hippocampal activity became especially labile, as detailed in their BOLD variability analysis.
That hippocampal volatility fits with broader evidence that psychedelics can both disrupt some memory tasks and intensify autobiographical recall. A peer-reviewed synthesis of memory outcomes found that higher doses can impair performance on standard memory tests while at the same time increasing the vividness of personal memories and often triggering re-experiencing of affectively intense life events. The review explicitly framed these effects as supporting the idea that psychedelics “fuel” autobiographical material, a conclusion that supports the focus on memory in therapeutic models. In interviews around this body of work, Carhart-Harris has described psychedelic sessions as occasions where people can re-encounter and emotionally process past experiences, consistent with the hippocampal findings.
Network Rewiring and Therapeutic Potential
The most closely watched clinical data come from primary trials that connect network changes to symptom shifts in treatment-resistant depression. One such study reported that psilocybin sessions were followed by altered resting-state connectivity within the DMN and in hippocampal–prefrontal circuits, along with measurable changes in cerebral blood flow. Notably, the researchers found that regional cerebral blood flow in the amygdala dropped by about 15 percent after treatment, a change they linked to reductions in depressive symptoms in their primary clinical-mechanistic report.
Additional work has probed how other hubs participate in this rewiring. A primary connectivity analysis of the thalamus showed that psilocybin does not affect this relay structure uniformly: intrathalamic components such as the mediodorsal and pulvinar nuclei displayed localized reorganization, and shifts in thalamocortical connectivity tracked with subjective drug intensity. Those findings, presented as evidence that thalamic effects are differentiated, give more anatomical precision to claims about “opening the gates” of perception. Together with DMN changes and amygdala blood-flow reductions, they suggest that ego dissolution and emotional relief may emerge from a coordinated, though temporary, reshaping of how self-related, sensory and affective regions talk to each other.
Broader Implications from LSD and Other Psychedelics
Psilocybin is not the only serotonergic psychedelic that appears to reconfigure brain networks in this way. A primary fMRI study of LSD found that the drug increased global functional connectivity and integration between networks that are usually more segregated, and that these connectivity boosts correlated with subjective ratings of ego dissolution. The authors interpreted their LSD connectivity data as support for the idea that reducing the dominance of tightly organized networks like the DMN allows for a more unified, less self-centered mode of consciousness.
These converging patterns across substances have fed into broader projections about future clinical applications. A recent review of psychedelic neuroscience argued that network-level effects, particularly on DMN integrity and cross-network integration, could underpin treatments for a range of psychiatric conditions, provided that dosing and psychotherapy are carefully structured. The review, which framed its discussion as a primary modern neuroimaging foundation for psilocybin work, suggested that controlled disruption of entrenched patterns might help patients escape rigid negative thinking, though it stressed that such claims remain provisional.
Claustrum, Gateways and the Fine Print of Rewiring
Beyond headline networks like the DMN and thalamus, newer work has turned to less familiar structures that are rich in 5-HT2A receptors, the main molecular target of classic psychedelics. The claustrum, a thin sheet of neurons tucked beneath the cortex, has emerged as one such hub. A primary fMRI study found that psilocybin altered BOLD variance and low-frequency amplitude within the claustrum and changed its connectivity with both DMN and task-control networks. The authors also linked measures of network integrity and modularity to claustrum connectivity, arguing that their BOLD-based claustrum findings were useful for grounding mechanistic stories about how psychedelics perturb consciousness.
These results complement the thalamic data by suggesting that rewiring is not just a diffuse, whole-brain phenomenon but also a set of targeted shifts in specific relay and integration hubs. When the claustrum and thalamus reorganize their communication with cortical networks, the usual hierarchy that keeps self, memory and perception neatly separated may loosen. That, in turn, offers a plausible route for why people report scenes that feel both vividly remembered and freshly constructed, as if perception and recollection were sharing the same stage.
Uncertainties and Future Directions
Despite the excitement around these findings, the evidence on long-term durability of network changes remains thin. The Nature precision-mapping study detected persistent alterations up to three weeks after dosing, but it did not extend beyond that window, and its 18-person sample leaves open major questions about individual variability. A peer-edited highlight stressed that the work was useful for identifying which effects lasted, yet it also emphasized the need for larger cohorts and longer follow-up to understand whether the brain truly “rewires” in a lasting way or simply relaxes and then recenters.
Memory effects raise similar uncertainties. While the peer-reviewed synthesis of memory outcomes supports the idea that psychedelics can intensify autobiographical recall, it also documents dose-related impairments on other memory tasks, hinting that not all memory changes are therapeutically helpful. Karl Friston has suggested that the future may lie in personalized psychedelic therapies that tailor dose, context and integration to each person’s network profile, using predictive-processing principles to guide that matching. For now, the best-supported claim is that psychedelics temporarily relax the brain’s usual constraints, allowing memory-rich signals to reshape how networks communicate; whether clinicians can reliably harness that rewiring without unintended consequences is the question the next generation of trials will have to answer.
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*This article was researched with the help of AI, with human editors creating the final content.
