Psychedelics are mind-altering substances that can strongly change how different parts of the brain talk to each other, especially within a network called the Default Mode Network (DMN). These effects go beyond a brief “trip.” They seem to quiet and reorganize the brain systems that shape our sense of self and our usual ways of thinking. This article looks at how psychedelics relate to the DMN, how they change brain connectivity, and what that might mean for mental health care.
Substances like psilocybin, LSD, and ayahuasca often reduce activity inside the DMN while increasing connections across other brain systems. Some researchers call this a “reboot.” Many people report lasting benefits after these experiences. By softening the DMN’s usual activity, psychedelics may open new communication routes in the brain and support a more flexible state of mind. Below, we cover what the DMN is, how it links to mental health, how psychedelics work in the brain, what imaging studies show, and the main ideas that try to explain these effects.
What is the Default Mode Network (DMN) in the Brain?
Think about what happens in your brain when you are not focused on a task-daydreaming, remembering, or thinking about the future. That is where the Default Mode Network comes in. It is a set of connected brain regions that becomes more active during rest and inward-focused thought. This ongoing background activity helps shape our sense of self and how we see the world. Brain scans show that, at rest, several areas increase their activity together. This pattern is what scientists call the DMN.
The DMN is far from idle. It supports self-reflection, mind-wandering, and autobiographical memory. It also helps us imagine ourselves in past or future situations. It plays a big part in ordinary awareness by supporting our ongoing sense of identity and helping us handle our inner life and the outside world.
Key Brain Regions Making up the DMN
The DMN is not a single spot in the brain. It is a group of regions that work together when we are at rest. Four main hubs often stand out:
- Medial prefrontal cortex (mPFC)
- Posterior cingulate cortex (PCC)
- Precuneus
- Angular gyrus
Other areas also play a role, such as the posteromedial cortex (PMC), middle temporal cortex (MTC), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG). Researchers study “functional connectivity” (FC)-how activity in these areas rises and falls together over time-to understand how the DMN works. The DMN is one of several resting-state networks (RSNs), which show slow, coordinated activity even when we are not doing a task.
Primary Functions and Activity Patterns of the DMN
The DMN often shows higher activity when we are not engaged with the outside world. If you put someone in a scanner with no task, DMN regions usually become active. When attention switches to a demanding task, DMN activity drops. This flip shows the DMN’s role in inward focus rather than outward attention.
The DMN supports introspection, reflection on personal history, and thinking about hopes and plans. It helps build the “narrative self” or “ego,” which becomes active in early childhood. As we grow, DMN connections strengthen into familiar pathways. These paths shape our default way of seeing and reacting to life. The DMN helps us keep a steady sense of “me” and separate ourselves from our surroundings, which likely helps us adapt and survive.
How is the Default Mode Network Related to Mental Health?
The DMN is helpful for building a healthy sense of self, but changes in its activity can also lead to distress. Many studies link altered DMN connectivity to mental health conditions. When the system that supports our inner story becomes overly rigid or misaligned, it can harm well-being by fueling negative thought loops and reducing mental flexibility.
Understanding these links helps guide targeted treatments. The DMN is tied to depression, anxiety, and obsessive-compulsive disorder (OCD). When this network is out of balance, people can get stuck in rumination and self-criticism. The sections below explain why the DMN’s balance matters for mental health and how its disruption can cause strong psychological problems.
DMN Overactivity and Common Psychiatric Disorders
Many studies report DMN overactivity in several mental health conditions. This pattern can act like an internal echo chamber that repeats negative thoughts and makes it hard to disengage. Depression, anxiety, post-traumatic stress disorder (PTSD), and OCD often show this trend.
When the DMN is overly engaged in self-focused thought, people can get stuck in rigid patterns and automatic negative thinking. For example, someone with anxiety may replay a social mistake over and over, worry about others’ opinions, and lose sleep. This nonstop inward focus can block joy and daily functioning.
Impact of DMN Dysregulation on Depression, Anxiety, and OCD
In depression, the mPFC-a key DMN hub-often shows elevated activity. This can drive rumination and negative self-talk. The brain becomes caught in loops about past failures or future fears, which makes it hard to feel positive or stay present.
In anxiety and OCD, DMN changes can fuel worry and intrusive thoughts. Strong links inside the DMN can keep these thoughts cycling. Treatments that help “reset” or reshape DMN activity may help loosen these loops and bring relief.
Role of Self-Referential Thought and Rumination
The DMN is deeply tied to the sense of “I.” A healthy self-image helps us function, but too much self-focus can be harmful. In depression and anxiety, attention can narrow to one’s own thoughts and feelings, cutting off a wider view.
Rumination-repetitive, passive focus on distress and its causes-is common in mood and anxiety disorders. It locks thinking into rigid tracks. The ego’s tight boundaries, fed by rumination, can create isolation from others, nature, and one’s deeper values. Changing how the DMN works can help people step back and see their inner life with more space and balance.
How Do Psychedelics Affect Brain Connectivity?
Psychedelics can strongly change how brain networks interact. Their vivid effects-hallucinations, mystical-type experiences, and shifts in self-perception-come from direct actions on brain chemistry. Unlike many standard psychiatric drugs that make small adjustments, psychedelics often cause a short-term reorganization of brain communication. This can help researchers study brain function and, in some cases, reset unhealthy patterns.
Renewed scientific interest has revealed more about how these drugs work. Researchers now map how psilocybin, LSD, and DMT act on receptors to produce shifts in connectivity. Below, we focus on serotonin receptors, especially 5-HT2A, and compare the effects of key substances.
Mechanisms of Classic Psychedelics on the Brain
Classic psychedelics mainly act on serotonin (5-HT) receptors. They can change awareness, sense of self, perception, and emotion. The term “psychedelic” comes from Greek roots meaning “mind” and “to make visible,” pointing to their ability to bring hidden mental content into view.
These substances are strong agonists at the 5-HT2A receptor. Activating this receptor raises the excitability of layer V pyramidal cells in the cortex, which boosts glutamate in the neocortex. This surge can make neural firing more irregular and reduce rhythmic brain activity. The “entropic brain” idea suggests psychedelics increase randomness in brain signals. With less rigid top-down control, the brain may become more flexible, which could help explain the therapeutic effects.
Role of 5-HT2A Receptors in Altering Connectivity
The 5-HT2A receptor is central to the psychedelic effect and its changes in connectivity. It is highly expressed in association areas like the DMN, frontoparietal network, and salience network. When psychedelics activate these receptors, communication patterns shift.
This activation appears to disrupt resting connectivity within the DMN and strengthen links between major networks. The pattern is not random. It reflects a shift in how regions communicate: less coupling within the DMN and more global connectivity. The size of these changes often tracks with how intense the experience feels. Researchers compare connectivity changes with 5-HT2A receptor maps to better link brain chemistry with imaging results.
Key Substances Studied: Psilocybin, LSD, and DMT
Psilocybin, LSD, and DMT (often taken as ayahuasca) are the most studied psychedelics for connectivity effects. Each has unique features but a shared impact on the DMN.
| Substance | Main Targets | Typical Duration | DMN Effect | Noted Clinical Signals |
|---|---|---|---|---|
| Psilocybin (psilocin) | 5-HT1, 5-HT2 (esp. 5-HT2A) | 4-6 hours | Strong drop in within-DMN FC; rise in global connectivity | Reduced depression/anxiety; signals in addiction/PTSD |
| LSD | 5-HT (esp. 5-HT2/5-HT1), dopamine | 6-12 hours | Lower within-DMN FC; higher between-network FC | Signals in alcoholism, depression, anxiety, cluster headaches |
| DMT (ayahuasca) | 5-HT2A; harmala alkaloids make DMT oral | 2-6 hours (ayahuasca) | Disrupts DMN; longer-term structural and network shifts reported | Antidepressant/anxiolytic signals; addiction/trauma support |
Psilocybin, from “magic mushrooms,” converts to psilocin after ingestion and binds several serotonin receptors, especially 5-HT2. Many studies show a strong drop in DMN connectivity-often between the mPFC and PCC-along with higher global connectivity. The experience lasts about 4-6 hours and can include joy, unity, fear, or anxiety. These DMN changes line up with decreases in anxiety and depression and may help with addiction and PTSD for weeks after dosing.
LSD binds widely to serotonin and dopamine receptors. Its effects often feel faster and more energetic than psilocybin and last 6-12 hours. LSD lowers connectivity inside the DMN (especially its medial-posterior parts) and raises connections across networks. People report joy and spiritual insight, but some feel paranoia and anxiety. Research suggests benefits for alcohol misuse and relief in depression, anxiety, and cluster headaches.
DMT, the main psychoactive in ayahuasca, becomes active by mouth due to harmala alkaloids in the B. caapi vine. Users often report deep spiritual experiences and a strong bond with nature. Ayahuasca disrupts DMN function during the 2-6 hour session. Long-term use links to thicker ACC, thinner PCC, more local and less global integration, and signals of antidepressant and anti-anxiety effects. It also relates to higher acceptance and mindfulness and benefit in addiction and trauma studies.
What Changes Occur in the Default Mode Network During Psychedelic Experiences?
Psychedelics often bring a marked shift in awareness, a sense of connection, and sometimes a brief loss of the usual sense of self. These effects match visible changes in brain activity, especially in the DMN. During the peak effects, the DMN moves away from its normal, tight, self-focused mode.
Imaging studies consistently show these shifts. Across substances, the pattern repeats: the DMN loosens its hold on the inner story, and pathways between networks open up. Below are the main changes, including reduced DMN activity and the experience known as ego dissolution.
Reduced DMN Activity and Increased Global Connectivity
Psychedelics often lower the normal synchronized activity within the DMN. It is like the brain’s inner editor takes a pause. At the same time, connections across the whole brain grow.
Instead of networks staying in their own lanes, the brain becomes more connected as a whole. Regions that rarely talk start exchanging signals more freely. This adds more possible brain states and flexibility. The move from a rigid, separated setup to a more connected one is a hallmark of the psychedelic state. It matches the idea of “shallower troughs” in brain activity, meaning more possible patterns and easier shifts between them.
Altered Functional Connectivity: Evidence from fMRI Studies
fMRI research shows that psychedelics reduce functional connectivity within the DMN. Psilocybin, for example, often decouples the mPFC and PCC.
Outside the DMN, a more complex picture appears: within-network links often drop, while links between networks rise. The DMN, which usually shows the opposite pattern of task-positive networks like the salience network (SLN) and frontoparietal network (FPN), becomes more coupled with them. Studies report higher FC between the anterior DMN and the SLN, FPN, and auditory network (AUD). Some changes last beyond the session. For instance, psilocybin can lower DMN integration and local modularity for up to three weeks in depressed patients, and DMN-hippocampus FC can remain reduced for weeks. These shifts often track with subjective intensity and type of experience.
Ego Dissolution and Its Relationship to DMN Disintegration
“Ego dissolution” or “ego death” is a common report during psychedelic states. The usual line between self and world softens, and people feel deeply connected. This often goes along with a breakdown of tight DMN function.
Work from Imperial College London links lower DMN activity with ego dissolution. Since the DMN helps keep the sense of “I,” weakening it can soften self-boundaries. People may feel they can “zoom out,” see the big picture, and feel part of a wider whole. Many find this healing. It can help them view their thoughts and feelings with more distance. While it can be scary for some, ego dissolution often brings insight and lasting shifts in outlook and behavior, likely because the brain briefly re-wires toward a less rigid self-model.
What Theories Explain Psychedelics’ Impact on the DMN?
The striking effects of psychedelics on the DMN and awareness have led to several ideas that link brain changes with lived experience. These models try to explain how short-term shifts in connectivity can lead to lasting benefits. They also connect brain dynamics, information flow, and the sense of self.
These ideas can guide research and help shape therapy. Below are three leading models: the Entropic Brain Theory, the REBUS model, and the CSTC/CCC models of connectivity.
Entropic Brain Theory
This theory, led by researchers like Robin Carhart-Harris, proposes that psychedelics raise brain entropy-more uncertainty and variability in neural activity. In daily life, the adult brain runs well-worn paths, especially in the DMN, which keeps entropy low. Psychedelics shake up those patterns and increase entropy.
With more randomness and less tight top-down control, the brain can explore more states. This resembles the open, curious state seen in early childhood. Aldous Huxley’s “reducing valve” idea maps here: the DMN filters incoming data; psychedelics open that valve wider for a time. Higher brain entropy may help “reset” rigid thinking and support change.
REBUS (Relaxed Beliefs Under Psychedelics) Model
REBUS builds on predictive coding and Bayesian inference. It suggests psychedelics “relax the precision” of prior beliefs while letting more bottom-up information in. Our brains constantly predict the world based on past learning. In many mental health conditions, these priors become too strong.
Under psychedelics, the grip of those priors loosens, and new sensory data carries more weight. The brain can then update its models of self and world. This can break old, negative patterns. Evidence shows that disrupting top-down control can lead to lasting gains in emotion regulation, with less negative mood and more positive mood after psilocybin. With lighter structural priors, the brain explores more connectivity patterns, which fits with unusual yet insightful experiences and increases in openness and flexibility.
CSTC and CCC Models of Brain Connectivity
Two other models add to this picture: the Cortico-Striatal-Thalamo-Cortical (CSTC) model and the Cortico-Claustro-Cortical (CCC) model.
CSTC model: 5-HT2A activation alters CSTC circuits, which can disinhibit the thalamus and reduce sensory gating. The thalamus filters sensory input to the cortex. With less filtering, more input floods the cortex. This may help explain vivid perceptions and ego dissolution. Evidence shows LSD raises excitatory thalamus-to-PCC connections and lowers ventral striatum-to-thalamus connectivity, pointing to stronger bottom-up flow.
CCC model: The claustrum has many 5-HT2A receptors and connects with much of the cortex. The CCC model suggests receptor activation in the claustrum disrupts higher cortical networks through cortico-claustro-cortical loops. Psilocybin can lower the BOLD signal in the claustrum, which predicts parts of the subjective experience. This model needs more data, but new tools may help test it.
These models can fit together. The feedforward thalamocortical loop in CSTC (more sensory input and ego dissolution) aligns with the REBUS idea of stronger bottom-up signals and looser priors. 5-HT2A activation in the claustrum could also drive CSTC changes and DMN shifts, raising entropy and plasticity. Future work may blend these ideas into a single account that better explains both the brain and the experience.
What Changes Occur in the Default Mode Network During Psychedelic Experiences?
Psychedelics often bring a strong change in awareness, a sense of unity, and sometimes a brief loss of the usual “self.” These are linked to clear shifts in brain networks, especially the DMN. During the peak effects, the DMN steps back from its tight, self-focused role.
Imaging supports this across substances. The repeating pattern is clear: the DMN eases its control, and links across networks open. Below are the main changes, from lower DMN activity to ego dissolution.
Reduced DMN Activity and Increased Global Connectivity
Across studies, psychedelics quickly disrupt resting connectivity inside the DMN. The brain’s inner storyteller quiets for a while. At the same time, links across the whole brain grow stronger.
Networks that usually stay separate begin to interact more. New patterns of communication appear, adding variety and flexibility. This shift toward a more connected brain is a core feature of the psychedelic state and matches the idea of more possible sub-states and smoother movement between them.
Altered Functional Connectivity: Evidence from fMRI Studies
fMRI work shows strong drops in DMN FC during psychedelic states. With psilocybin, the mPFC and PCC often decouple.
Meanwhile, between-network FC rises. The DMN, which usually shows the opposite pattern of task-positive networks like the SLN and FPN, becomes more aligned with them. Studies find higher FC between the anterior DMN and SLN, FPN, and AUD. Some effects last for weeks, including lower DMN integration and reduced modularity in depressed patients, and reduced DMN-hippocampus FC. These changes often match the intensity and quality of the subjective experience.
Ego Dissolution and Its Relationship to DMN Disintegration
Ego dissolution-softening of the boundary between self and world-is a frequent report. It pairs with a breakdown of tightly coupled DMN activity.
Research links lower DMN function with this experience. When the DMN’s role in maintaining the “I” weakens, people can step back and feel part of a larger whole. Many find this calming and insightful. It can help them view thoughts and feelings with greater distance. While it can be unsettling for some, ego dissolution is often tied to deep insight and lasting positive change. A brief shift in brain wiring may allow a less rigid sense of self.
What Are the Therapeutic Implications of DMN Modulation by Psychedelics?
The DMN and connectivity changes seen with psychedelics matter for treatment. By loosening rigid patterns and promoting a more connected brain state, these substances may offer a window for change. This can help people step out of negative self-stories and unhelpful habits common in many psychiatric disorders.
Psychedelic-assisted therapy aims to use these brain shifts for lasting clinical gains. Results are promising in depression, PTSD, and addiction. At the same time, important challenges and risks call for careful clinical settings and trained support.
Potential Benefits in Treating Depression and PTSD
Depression often shows high and rigid DMN activity, especially in the mPFC, which drives rumination. Psychedelics lower this activity and loosen internal DMN links, giving a break from negative loops. This may act like a “reset,” opening the door to new, healthier pathways.
Psilocybin can reduce depression scores for months in some studies, likely by making the DMN less rigid. In PTSD, the DMN’s links to the salience network and its role in self-awareness are important. PTSD often shows strong salience network connectivity and intense threat responses. By shifting these networks, psychedelics may help people process trauma with less fear and avoidance. Gains in overall network integration may support these lasting benefits.
Impacts on Addiction and Obsessive Disorders
Addiction and OCD involve repetitive thoughts and behaviors that feel hard to stop. These may reflect an overactive, rigid DMN. Psychedelics can disrupt these patterns and offer a chance to reframe habits and beliefs.
In addiction, psilocybin and LSD have shown signals for stopping smoking and reducing alcohol use. Powerful, meaningful experiences and ego dissolution can shift perspective and reduce craving and isolation. In OCD, breaking rigid DMN loops may reduce intrusive thoughts and compulsions. With more neural flexibility, people may build new coping skills and less obsessive thinking.
Current Challenges and Risks of DMN-Focused Psychedelic Therapies
Despite promise, many hurdles remain. Psychedelic experiences vary widely. Some are difficult, with fear, anxiety, or paranoia. These risks highlight the need for careful, supportive, and professional settings. Self-medicating is strongly discouraged.
Research also faces limits. Many studies are small and include people with prior psychedelic use, which can affect results. It is still hard to say whether DMN changes directly drive clinical gains or are a byproduct. Best dose, timing, and how to combine with therapy are still under study. Ethical rules and regulations also need attention. Progress will require larger studies, strong training for clinicians, and careful policy work to bring these tools into care safely.
Common Questions about Psychedelics and DMN Connectivity
As interest grows, many people ask how psychedelics affect the DMN, whether all psychedelics act the same way, and how long changes last. These questions help clarify what makes these drugs different from other treatments and where research needs to go next.
Answering them helps make the science clearer and supports safe, effective use. Here are some common questions and brief answers.
Are Changes in the DMN Specific to Psychedelics?
Psychedelics are well known for changing the DMN, but other substances and practices can also affect it. For example, alcohol can lower connectivity within the DMN, which may relate to feelings of euphoria, but it does not strongly change how the DMN connects with other networks.
Ketamine (at doses that change awareness) can lower DMN FC and shift links between the DMN and other networks. Salvinorin A shows a similar pattern: lower within-network FC and higher between-network FC. Practices like mindfulness meditation also lower DMN activity and change how beliefs and attention are weighted. What seems to stand out for psychedelics is the mix of increased global integration, network rebalancing, and plasticity, which may help explain their therapeutic potential.
Do All Psychedelics Affect the DMN Equally?
Classic psychedelics share broad features, but their effects on the DMN are not identical. Differences in receptor binding and subjective effects lead to distinct connectivity patterns. All three-psilocybin, LSD, and ayahuasca-tend to lower within-DMN FC and raise global connectivity, but the details vary.
LSD binds to a wider range of receptors and often yields broader shifts in between-network connectivity and in regions like the basal ganglia and thalamus compared with psilocybin. People often describe it as faster and more energizing. Ayahuasca also disrupts the DMN, and long-term use links to structural changes like thicker ACC and thinner PCC. Dose matters too: higher LSD doses reduce oscillatory power more than lower doses. These differences suggest each psychedelic has a unique neural “signature.”
How Long Do Psychedelic-Induced DMN Changes Last?
Benefits can outlast the session by weeks or months. Many brain patterns return to baseline within days, but some shifts endure.
With psilocybin, lower DMN integration and reduced local modularity can last up to three weeks in depressed patients. DMN-hippocampus FC can remain reduced for at least three weeks, which may reflect ongoing changes in self-related circuits. Clinically, psilocybin can relieve depressive symptoms for up to six weeks in some studies, likely linked to broader network integration and lower modularity. Long-term ayahuasca use has been tied to structural changes in the ACC and PCC. These lasting shifts may support the “reset” that helps people keep healthier patterns of thought and behavior.
Key Takeaways on the Default Mode Network and Psychedelic Brain Connectivity
The story of the DMN and psychedelics shows how flexible the brain can be and how change is possible. The DMN, which helps tell our inner story, can become rigid in mental illness, trapping people in rumination and self-criticism. Psychedelics often loosen this pattern and open new ways for the brain to connect, which can support healing.
Across studies, classic psychedelics tend to lower connectivity within the DMN and raise connectivity across the brain. This is more than a short-lived burst of activity. It is a shift from a separated, modular setup to a more connected and flexible one. With higher brain entropy, long-held beliefs can soften, and people can see themselves and the world in a new light. Ego dissolution is not just a strange feeling; it has clear brain links and can help people gain insight and adopt a kinder, wider view of their struggles.
Therapeutic signals are promising in depression, PTSD, and addiction. By offering a kind of “reset,” psychedelics can help people step out of stuck patterns and build flexibility. While research quality and clinical methods still need work, evidence across studies and models points in the same direction. The DMN is no longer seen as idle background activity; it is central to mental health. Psychedelics are now tools that help us study it and use its shifts to support well-being and open new directions in care.