What is the default mode network?

The default mode network (DMN) is a set of brain regions — including the medial prefrontal cortex, posterior cingulate cortex, and precuneus — that show coordinated activity when a person is not focused on the external environment, and is instead engaged in self-referential thought: remembering, planning, imagining, or reflecting on themselves. It was formally described in the early 2000s using resting-state fMRI.

How do psychedelics affect the DMN?

fMRI studies from Carhart-Harris and colleagues, and subsequent work by other groups, have reported that classical psychedelics such as psilocybin, LSD, and ayahuasca acutely reduce the integrity and internal connectivity of the DMN, while increasing communication between brain networks that are normally more segregated. This pattern has been proposed as a neural correlate of the subjective 'ego dissolution' many participants report.

Why might that matter for depression or trauma?

Rigid, self-focused rumination — a persistent inward loop — is a documented feature of depression, and DMN hyperconnectivity has been observed in depressed patients. The hypothesis is that temporarily loosening the DMN's dominance, in a supported setting, gives patients an opportunity to step outside habitual self-narratives and re-integrate afterward. It is a hypothesis, not settled fact.

Is 'the DMN is reset' a proven claim?

No. The claim that psychedelics permanently 'reset' the DMN is stronger than the current evidence supports. What the evidence supports is that classical psychedelics acutely disrupt DMN activity and that this correlates with subjective experience and, in some studies, with clinical outcome. Longer-term structural changes are still being characterized.

Default Mode Network Psychedelics Explain

The default mode network is one of the most studied structures in modern neuroscience, and it is central to how researchers currently explain why psychedelics can produce experiences that feel — and sometimes measurably are — durable rather than transient. This piece walks through what the DMN actually is, what the peer-reviewed literature reports about psychedelics' effect on it, and where the strong claims outrun the evidence.

Learn what actually happens during the ayahuasca ceremony itself — ritual structure, facilitator's role, the purge, and next-morning integration.

What the DMN Is

The default mode network — formally described using resting-state fMRI in the early 2000s — is a set of brain regions including the medial prefrontal cortex, posterior cingulate cortex, and precuneus, along with parts of the inferior parietal lobule and medial temporal lobe. It is the network that is most active when a person is notexternally focused: when they are remembering, planning, imagining the future, or thinking about themselves and other people.

The DMN in Depression

A large body of resting-state fMRI research has associated depression with altered DMN activity — often described as hyperconnectivity within the network and difficulty disengaging from self-referential thought. Persistent rumination is not just a symptom of depression; it appears to be tied to the way the DMN is functioning, which is part of why researchers have looked at DMN dynamics as a mechanistically meaningful target for intervention rather than a downstream correlate.

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What Psychedelics Appear to Do

In a series of neuroimaging studies beginning in 2012, Robin Carhart-Harris and colleagues reported that psilocybin acutely reduces blood flow and coordinated activity in DMN hub regions, while increasing communication between networks that are normally more segregated from each other (Carhart-Harris RL, et al. Proc Natl Acad Sci USA. 2012). A related line of research has reported comparable network-level effects with ayahuasca in the context of depression treatment (Palhano-Fontes F, et al. Curr Top Behav Neurosci. 2022). A follow-up fMRI study in patients with treatment-resistant depression linked reduced DMN integrity after psilocybin therapy to the clinical brain mechanisms researchers believe underlie symptom improvement (Carhart-Harris RL, et al. Sci Rep. 2017) — an early step toward a broader framework in which classical psychedelics increase the diversity of moment-to-moment brain states, with the DMN's loosened grip as one signature of that shift.

The 2022 Longitudinal Follow-up

The 2017 Scientific Reports fMRI follow-up in treatment-resistant depression found that the acute reduction in DMN integrity during dosing sessions was associated with symptom improvement measured afterward, linking the acute neuroimaging signature to a clinical outcome in the same participants rather than leaving the two as separately observed facts. More recent reviews of psychedelic-induced neuroplasticity (Weiss F, et al. Brain Sci. 2025) situate that finding within a broader mechanism: activity-dependent structural changes — new dendritic growth and synaptic remodeling — that plausibly outlast the acute network shift and could explain durable clinical change beyond the dosing day itself.

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Why That Might Produce Lasting Change

If the DMN is the substrate of habitual self-narrative, and depression involves a stuck, inward-turned version of that narrative, then a temporary, supported disruption of the DMN may open a window in which patterns can reconfigure. This is the working hypothesis behind much of contemporary psychedelic therapy research, and it is consistent with the clinical observation that the subjective intensity of the experience often correlates with clinical outcome. It also explains why "set and setting" — preparation, environment, integration — are treated as clinically relevant rather than peripheral.

What the Evidence Does Not Say

The evidence does not support the strong claim that a single psychedelic experience permanently "resets" the brain. What it supports is: acute DMN disruption during the experience, meaningful correlations between that disruption and subjective and clinical outcomes, and — in the case of psilocybin for depression — genuine but still-early evidence of sustained effects in controlled trials. The DMN framework is a promising organizing story for what these compounds do, but it is not a completed neuroscience.

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Why the DMN Is Not the Whole Story

The DMN framework is useful but incomplete. Psychedelics also modulate the salience network, the frontoparietal control network, and thalamocortical connectivity, and the broader finding across neuroimaging studies is that between-network segregation decreases while moment-to-moment global integration increases. The "loosened DMN" story captures one striking piece of that broader shift, but it is not the whole shift. Newer analyses using dynamic functional connectivity and complexity measures argue that what really changes on psychedelics is the diversity of accessible brain states over time, of which DMN disintegration is a signature rather than the cause.

Ego Dissolution as a Correlate

One of the more replicated findings across the neuroimaging literature is that the degree of subjective ego dissolution during a psychedelic experience correlates with the degree of acute DMN disintegration measured on fMRI. This is a rare instance of a subjective psychological construct — the felt loss of ordinary self-boundaries — mapping onto a specific neural signature. It doesn't prove the DMN is the seat of the self; it does suggest the DMN is a load-bearing substrate for the ordinary sense of continuous self-narrative that ego dissolution disrupts. Whether that dissolution is therapeutically necessary, or merely correlated with therapeutic outcome, is one of the open questions the Phase 3 trials will help answer.

Implications for Practice

If the working hypothesis — acute network disruption creates a plasticity window that integration then consolidates — is even approximately right, several practical implications follow. The pre-session state matters: entering the experience anxious or distracted biases which regions are active and which shift. The environment matters: external context shapes what the loosened network reorganizes toward. And the integration period matters: what a patient does with new patterns of thought and feeling in the days and weeks after a session probably determines whether the acute change consolidates or dissipates. None of this is unique to psychedelic therapy — it is standard for any intervention that produces a temporary window of increased plasticity — but it is why responsible programs treat set, setting, and integration as parts of the treatment rather than accessories to the drug.

A Brief Note on Sanctuary Tulum

Sanctuary Tulum's work with ayahuasca, ibogaine, 5-MeO-DMT, and psilocybin is framed around preparation, medically supervised administration, and integration — the parts of the process the neuroscience suggests actually matter. For details, see our ayahuasca retreat, psilocybin therapy, and 5-MeO-DMT ceremony pages.