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For decades we have treated depression as though the primary question were how to suppress its symptoms. We developed medications that alter serotonin, norepinephrine, dopamine, and other neurotransmitter systems, and for many people those medications have provided genuine relief. But the contemporary research on psilocybin is asking a fundamentally different question. Instead of asking only how to reduce depressive symptoms, researchers are beginning to ask whether the brain and the psychological sense of self can be moved temporarily into a state in which deeply entrenched patterns become more available for revision.
This is why I believe psilocybin is potentially far more important than simply another antidepressant. The emerging psychedelic research is pointing toward a different model of psychological healing, one in which depression may involve not merely a deficit of neurotransmitters but an excess of rigidity. The depressed mind often becomes trapped in repetitive loops of self criticism, shame, rumination, hopelessness, and certainty about the future. Psilocybin appears capable of temporarily loosening that rigidity while increasing neural and psychological flexibility. In other words, it may not simply make someone feel better. It may create a period in which the system through which that person has been interpreting himself and his life becomes more capable of changing.
Few researchers have contributed more to this way of understanding psychedelic medicine than Robin Carhart-Harris. Now the Ralph Metzner Distinguished Professor of Neurology, Psychiatry and Behavioral Sciences at the University of California, San Francisco, Carhart-Harris founded the Centre for Psychedelic Research at Imperial College London and has spent years studying psilocybin, LSD, DMT, MDMA, consciousness, depression, brain networks, and the mechanisms through which psychedelic experiences can produce enduring psychological change. (Carhart-Harris Lab) His work gives us something much more valuable than another claim that psychedelics “work.” It offers a developing theory for understanding why they may work.
The Buddha said, “Life is suffering” 2500 years ago. As someone how has live in Southeast Asia for over 8 years where there is a tremendous amount of poverty and slavery, you see a deep level of this truth, however people here dont have the money for western medications. They also don’t have the luxury of taking on the everything is the brain theory because they don’t have the money to treat the brain with American pharmaceuticals. People more often deal with life in other ways. Using meditation and music are some of the primary easy methods. People suffering from chronic depression often do not merely experience sadness. Chronic depression feels like certainty; “Nothing will change.” “There is something wrong with me.” “I always fail.” “People leave me.” “My future will be like my past.” After these conclusions have been repeated for years, they stop being experienced as interpretations. They become reality.
This is one reason depression can be so difficult to treat. A person may understand intellectually that the beliefs developed during childhood are inaccurate and yet continue to experience them emotionally as true. A client may understand that a critical father caused him to internalize shame. He may know his father’s cruelty was not evidence of his own inadequacy. He can explain attachment theory, trauma, family dynamics, and cognitive distortions. Yet the moment a partner becomes distant or someone criticizes him, the old nervous system returns immediately: I am defective. I am unwanted. Something is wrong with me.
This difference between intellectual knowledge and reorganized experience is central to psychotherapy. Insight is necessary, but insight alone does not always change the deeper organization through which the person experiences himself.
Carhart-Harris’s work provides a compelling neuroscientific language for this problem. His entropic brain hypothesis proposed that ordinary waking consciousness is maintained by relatively constrained and organized patterns of neural activity. Psychedelics temporarily increase the entropy, or diversity, of brain activity, loosening the ordinary organization of consciousness. In 2026, Carhart-Harris revisited the theory in Brain and noted that more than a decade of research had accumulated substantial support for the general relationship between expansive states of consciousness and increased neural entropy. (Oxford Academic)
This is where the psychedelic model becomes particularly relevant to depression. If depression is partly characterized by excessively constrained thinking, repetitive self reference, rumination, and rigid predictions about oneself and the world, then increasing the flexibility of the system may allow new information to enter.
Carhart-Harris and neuroscientist Karl Friston later developed this idea further in a model called REBUS, an acronym for “Relaxed Beliefs Under Psychedelics.” Their argument is that the brain functions partly as a prediction system. It continuously develops models about what is happening, what will happen next, what other people will do, and who we ourselves are. These expectations are sometimes called “priors.”
Normally this predictive system is extraordinarily useful. If I walk into my kitchen, I do not need to rediscover from the beginning what a refrigerator is. The brain uses previous experience to predict the world. But the same system can become pathological when certain predictions become so heavily weighted that contradictory evidence is no longer allowed to change them.
A depressed person may have an extraordinarily powerful prior that says, I am unlovable. Another might carry, People will abandon me. Someone with longstanding shame may unconsciously predict, If anyone actually knows me, they will reject me. These beliefs filter experience. Ambiguous information is interpreted in their favor, while contradictory experiences are minimized or ignored.
Carhart-Harris and Friston proposed that psychedelics temporarily reduce the precision or authority of these high level beliefs, allowing information that would ordinarily be suppressed to move upward through the system. Their model specifically proposes that psychedelics can weaken “pathologically overweighted priors” and make them more available for revision. Importantly, they also argued that intention, care, and context can help guide what happens during this period of increased openness. (PubMed Central (PMC))
This is an extraordinary idea for psychotherapy.
The psychedelic is not necessarily giving the patient a new belief.
It may be temporarily weakening the dictatorship of the old one.
The self image is not a single thought stored somewhere inside the head. It is a complicated psychological construction built from memory, attachment, bodily experience, shame, emotion, language, social feedback, expectation, and thousands of repeated interactions.
A child who experiences chronic criticism may eventually move from “My father criticizes me” to “There is something wrong with me.” A child who repeatedly experiences abandonment may eventually move from “My mother leaves” to “I am not worth staying for.” A person repeatedly humiliated may come to believe, “If people see who I really am, they will reject me.”
These conclusions become extraordinarily powerful because they are rehearsed over and over again. They become predictions about future experience. The person begins selecting evidence that confirms them. Eventually the belief is no longer experienced as a belief.
It feels like identity.
This is where psilocybin becomes particularly interesting. If REBUS is broadly correct, the psychedelic state may temporarily weaken the certainty attached to these entrenched self models. For perhaps the first time in decades, “I am defective” can become “I learned to experience myself as defective.” “I am broken” can become “I was hurt.” “I am shameful” can become “I experience shame.”
That movement from identity to relationship with experience is one of the most important movements that can occur in psychotherapy.
Carhart-Harris’s early clinical research made this theory clinically tangible. In a 2016 Imperial College London study, people with treatment resistant depression received two supported psilocybin sessions. The research was small and open label, but it provided an important early signal that people whose depression had persisted despite conventional treatment could experience substantial improvement after psychedelic treatment.
Follow up neuroimaging provided another important clue. In a study of patients with treatment resistant depression, depressive symptoms decreased in all 19 participants at one week, and 47% still met response criteria at five weeks. Brain imaging showed changes involving the amygdala, default mode network, and connectivity between several regions associated with self related and emotional processing. The researchers proposed what they called a “reset” mechanism. (Nature)
That word is imperfect, because the brain is not literally returned to some original factory setting. But psychologically it conveys something useful. The system appears capable of moving out of an established configuration and reorganizing.
This is profoundly different from telling a patient with longstanding depression that their nervous system is simply defective and needs continuous chemical correction.
It introduces another possibility: perhaps the depressed system has become too stable.
The findings at Johns Hopkins strengthened the case considerably. In a randomized clinical trial of adults with major depressive disorder, two psilocybin sessions combined with psychological support produced very large reductions in depression. Seventy one percent of participants met criteria for clinically significant response at both one and four weeks, while 54% were in remission at week four. Effect sizes on clinician rated depression were exceptionally large. (JAMA Network)
Another large randomized trial involving 104 adults found that a single 25 mg psilocybin session combined with psychological support produced a clinically significant reduction in depressive symptoms and functional disability that remained evident through the six week study. At the end of the study, sustained response was substantially more common with psilocybin than with the active placebo. (JAMA Network)
These results matter because the treatment model is fundamentally different from the usual expectation that a psychiatric medication must remain continuously present in the body to keep producing an effect. Psilocybin leaves the body relatively quickly. Yet meaningful psychological changes can persist far beyond the acute drug state.
That means something is being learned.
Something is changing.
The biological event is producing consequences that outlast the presence of the molecule itself.
This brings us to neuroplasticity. Psilocybin is increasingly discussed as a psychoplastogen, a substance capable of rapidly promoting forms of structural and functional neural plasticity. Neuroplasticity is the capacity of the nervous system to modify its connections and patterns in response to experience.
Learning depends on plasticity. Attachment depends on plasticity. Trauma depends on plasticity. Meditation depends on plasticity. Psychotherapy depends on plasticity.
The psychedelic question is whether psilocybin can temporarily enhance this natural capacity for change.
Animal studies have shown that a single psilocybin dose can rapidly increase the size and density of dendritic spines in frontal cortical neurons, with some changes persisting for weeks. Dendritic spines are small structures involved in neuronal communication. These findings do not mean that every new synaptic connection represents psychological healing, but they provide biological evidence that psilocybin can affect the physical architecture through which neurons learn and communicate.
Human research is now beginning to provide equally intriguing evidence. In May 2026, researchers from UCSF and Imperial College reported anatomical and functional changes in the human brain lasting as long as a month after a single high psilocybin dose. Increased acute neural entropy predicted psychological insight the next day, which in turn predicted improved well being a month later. Imaging also suggested increased integrity or density in white matter pathways at the one month follow up. (UCSF)
Carhart-Harris summarized the importance of these findings succinctly: the psychedelic experience itself, and the brain state accompanying it, may be an important component of subsequent mental health improvement.
That finding is crucial because it challenges the idea that the subjective psychedelic experience is merely an irrelevant side effect of a chemical treatment. The experience itself may be part of the mechanism.
This also helps explain why the language of flexibility appears repeatedly throughout psychedelic research. Johns Hopkins researchers have reported that psilocybin therapy increases cognitive and neural flexibility in people with major depressive disorder. (PubMed Central (PMC)) Carhart-Harris’s own imaging work similarly suggests that psilocybin increases communication between brain systems that are ordinarily more separated.
In August 2026, UCSF summarized new research from Carhart-Harris and colleagues as showing that psilocybin fostered greater connectivity between brain regions in depressed participants, potentially freeing them from longstanding patterns of rumination and excessive self focus. Importantly, the same type of increased network integration was not observed in participants receiving escitalopram. (UCSF Psychiatry and Behavioral Sciences)
I find this distinction much more interesting than simply asking which medication wins on a depression questionnaire.
The deeper question is whether two treatments are changing depression through fundamentally different processes.
A conventional antidepressant may reduce symptoms. Psilocybin may also alter the rigidity of the system that generates and perpetuates those symptoms.
The August 2026 Nature study by Stoliker, Novelli, Khajehnejad and colleagues, which included Carhart-Harris as a coauthor, takes this entire theory another step forward.
The researchers studied 62 people who had never previously used psychedelics, making it the largest single site acute psychedelic neuroimaging study reported at the time. Participants underwent fMRI and EEG while resting, meditating, listening to music, and watching a movie both before and during psilocybin. (Nature)
Earlier psychedelic neuroscience often described the psychedelic brain primarily in terms of entropy, desynchronization, and disorder.
The new study found something more interesting.
Psilocybin did disrupt ordinary neural organization, but beneath that apparent disorder researchers found a latent order. Brain activity became dynamically aligned with what the participant was actually experiencing.
Meditation produced one pattern.
Music produced another.
Watching a movie produced another.
Rest produced another.
As the psychedelic experience deepened, these contexts became increasingly distinguishable from one another in brain activity. If psilocybin were merely adding random neural noise, the opposite should have happened. Instead, the researchers found increasingly structured, context sensitive organization. (Nature)
This is a remarkable finding because it extends the entropic brain theory rather than overturning it. The psychedelic brain becomes less constrained by its ordinary organization, but that greater freedom can allow it to reorganize around the immediate environment.
Chaos was not the final story.
Flexibility was.
The researchers described an especially interesting subjective state as embeddedness. This refers to the experience of feeling continuous with the surrounding environment rather than experiencing oneself as an entirely separate object moving through it.
Participants reporting stronger positive self dissolution and dissolution of the ordinary boundary between self and surroundings showed stronger context alignment in their brain activity. The strength of this alignment also predicted changes in mindset the following day. Half of the 62 participants described the experience as being among the most meaningful experiences of their lives. (Nature)
This gives neuroscience an extraordinary window into something psychedelic users, contemplatives, mystics, and Indigenous ceremonial traditions have described for generations.
The ordinary sense of separateness may itself be a construction.
Under psilocybin, the neural systems involved in internally directed processing and externally directed perception become more integrated. In particular, changes involving the default mode network and visual network appear to help create conditions in which self and environment become less rigidly separated. (Nature)
For someone whose depression has become organized around a painfully isolated self, the relevance is obvious.
The depressive voice says, “I am this.”
Embeddedness introduces the possibility that the “I” itself is not as fixed or separate as it ordinarily appears.
Perhaps the most important implication of the 2026 Nature study concerns set and setting.
For generations, people working with psychedelics have insisted that the psychological state of the person and the environment surrounding the experience profoundly influence what occurs.
Western pharmacology has often treated this as secondary. The molecule is considered the “real” treatment; music, relationship, ritual, intention, environment, and meaning are regarded as variables surrounding the pharmacological action.
But if the psychedelic brain literally reorganizes itself differently according to whether the person is meditating, listening to music, resting, or watching a film, then context is not simply an accessory.
Context is entering the neural dynamics of the psychedelic state itself. (Nature)
Carhart-Harris’s current UCSF laboratory is now explicitly studying this interaction. Its Set and Setting Study is designed to test how different environments interact with psilocybin in controlled conditions. (Carhart-Harris Lab)
This is an important moment in psychedelic science.
Western neuroscience is beginning to investigate experimentally what ceremonial traditions have insisted for generations: the substance and the setting cannot always be meaningfully separated.
This deserves much more attention than it usually receives.
A ceremony organizes attention. Music organizes emotion. Ritual creates expectations and meaning. A trusted guide provides relational safety. Community places an altered state within a shared framework. Preparation influences what the person expects to encounter. Integration influences what is learned afterward.
If psilocybin simultaneously increases plasticity and makes brain activity more dynamically responsive to environmental context, then these elements may influence what the nervous system learns during the psychedelic state.
In other words, ceremony may not merely be ancient decoration surrounding an active chemical.
Parts of ceremony may function as a technology for organizing heightened psychological receptivity.
This does not mean science must accept every traditional cosmological interpretation literally. It means science should become considerably more humble about the assumption that Western pharmacology identified the important part of psychedelic healing while everything Indigenous cultures placed around the medicine was irrelevant.
The newest neuroscience increasingly suggests otherwise.
Paul Stamets has spent much of his career arguing that mushrooms deserve far more scientific attention than Western medicine has historically given them. He is a mycologist rather than a psychiatrist, and his contributions should be represented accurately, but his work has helped bring public and scientific attention to the extraordinary biochemical complexity of fungi and to the possibility that different mushroom species may have neurological and psychological effects worthy of serious research.
Stamets was a coauthor of a large naturalistic study following 953 people who microdosed psilocybin and 180 non microdosing participants for approximately one month. The microdosing group showed small to medium improvements in mood and mental health that were broadly consistent across age, gender, and the presence or absence of mental health concerns. Older participants also showed some psychomotor improvements. (Nature)
This research should not be confused with the stronger randomized clinical evidence involving full psychedelic doses. Microdosing and high dose psychedelic therapy are different interventions and may operate differently. But Stamets’s work is relevant to the larger scientific shift because it demonstrates how quickly public experimentation with mushrooms has outpaced conventional research and how much remains to be investigated.
His interest in combining psilocybin with lion’s mane mushroom and niacin has also generated hypotheses about potential synergistic effects. The 2022 observational study did not find that adding lion’s mane and niacin enhanced mood improvements beyond psilocybin microdosing alone, although some older participants showed psychomotor differences. (Nature) That is precisely why more rigorous research is needed. A pro mushroom position does not require turning every hypothesis into a conclusion. It requires taking fungal medicine seriously enough to investigate it properly.
One of the most important changes occurring within psychiatry is the reconsideration of subjective experience itself.
Conventional pharmacology often tries to separate therapeutic action from subjective effects. If a medication produces altered perception, unusual emotions, or mystical experiences, these may be regarded as side effects that ideally could be engineered away.
Psychedelic research repeatedly challenges that assumption.
Carhart-Harris’s 2026 neuroplasticity study found that greater acute entropy predicted greater psychological insight, and that insight predicted later improvements in well being. (UCSF) The Stoliker Nature study found that deeper positively experienced self dissolution and boundary dissolution corresponded with stronger context aligned neural organization and subsequent mindset change. (Nature)
These findings suggest that what happens phenomenologically may matter.
The psychological experience may be part of the treatment.
This is not a minor distinction.
It means we cannot understand psychedelic therapy by studying only the receptor.
We also have to study the person.
Consider a person who has been depressed for twenty years and has spent much of that time carrying the belief, “There is something fundamentally wrong with me.” They may have undergone years of therapy. He understands that his father was emotionally abusive. He knows the shame originated in childhood. He understands cognitive distortions and attachment wounds.
Yet the belief persists. Maybe it even was a part of the religious culture they grew up in with thier family that they love.
During an appropriately supported psychedelic experience, something different may occur. He does not simply think, “Perhaps I am not defective.” Instead, for the first time he experiences the old belief as an object within consciousness rather than as consciousness itself.
The distinction is difficult to describe intellectually but clinically enormous.
“I am defective” becomes “There is a part of me that learned to believe I was defective.”
That movement creates psychological space.
And psychological space creates choice.
The growing evidence for neuroplasticity has naturally raised questions about whether psychedelic compounds may eventually have applications beyond mood disorders, including mild cognitive impairment and neurodegenerative illness.
This area should be discussed with excitement and accuracy. Psilocybin has not been demonstrated to cure Alzheimer’s disease or reverse dementia. Current studies involving people with early Alzheimer’s disease or mild cognitive impairment have primarily focused on depression, existential distress, safety, and quality of life.
But the scientific question is legitimate.
A compound capable of influencing structural plasticity, synaptic organization, neural connectivity, psychological flexibility, and potentially neurotrophic signaling naturally raises questions about whether some of those mechanisms could eventually become relevant to neurodegenerative disease.
The correct response is not to declare that mushrooms cure dementia.
It is to recognize that the biology now justifies serious investigation.
There is another dimension of psychedelic medicine that I believe psychology needs to confront honestly.
Western psychology has repeatedly encountered sophisticated practices from outside Europe and North America, initially dismissed them as primitive or religious, then extracted useful elements, renamed them, and incorporated them into Western clinical practice.
Mindfulness is an obvious example.
Meditation practices that existed within Buddhist psychological systems for more than two thousand years eventually entered Western psychology stripped of much of their original philosophical and cultural framework. In my earlier work on Euro American ethnocentrism in psychology, I argued that Western psychology has frequently adopted practices from Asian contemplative systems without adequately acknowledging the psychological theories in which those practices developed.
Psychedelic medicine presents the same danger.
Western medicine did not discover psychedelic mushrooms.
Indigenous communities in Mexico maintained relationships with psychoactive mushrooms long before modern psychiatric researchers became interested in psilocybin.
The modern Western psychedelic narrative is inseparable from María Sabina, the Mazatec curandera who allowed R. Gordon Wasson to participate in a mushroom ceremony in Oaxaca in 1955. Wasson’s subsequent Life magazine article exposed the practice to an enormous Western audience. Albert Hofmann later isolated and synthesized psilocybin and psilocin.
Western accounts frequently describe what followed as a scientific discovery.
But the mushrooms had already been discovered.
Their capacity to alter consciousness was already known.
Ceremonial methods for using them already existed.
The communities using them had already developed ideas about preparation, relationship, meaning, ritual, and healing.
Western science contributed enormously valuable things: chemical isolation, controlled dosing, receptor pharmacology, neuroimaging, clinical trials, and standardized outcome measures.
But science did not begin the story.
The colonial history surrounding psychedelic substances is complicated and should not be reduced to one simple cause. Psilocybin prohibition in the twentieth century involved political fear of counterculture, sensational media reporting, drug control policy, and broader cultural anxieties about altered states.
But the larger history of psychedelic prohibition cannot be separated entirely from colonialism and racialized distrust of Indigenous spiritual practices.
The history of peyote makes this particularly visible. Indigenous ceremonial use was attacked repeatedly by colonial and later American authorities, often in the context of broader attempts to suppress Native religions and assimilate Native peoples.
This matters because Western institutions repeatedly claimed the authority to decide which forms of altered consciousness were sacred, which were pathological, which were criminal, and which might eventually become medicine.
A mushroom can exist for generations as medicine within one culture, become classified as a dangerous drug by another, and then reappear decades later as an experimental pharmaceutical.
The molecule did not change.
Authority changed.
And now the economic landscape is changing with extraordinary speed.
The pharmaceutical and biotechnology industries that once had little serious interest in classical psychedelics are investing enormous sums into psychedelic and psychedelic inspired compounds. Companies are developing psilocybin formulations, next generation neuroplastogens, non hallucinogenic analogues, and other molecules designed to capture elements of psychedelic induced plasticity.
This movement is itself evidence of a paradigm shift.
It does not prove that every psychedelic treatment will succeed.
It shows that mainstream biomedical institutions now consider the field scientifically and commercially serious.
The same compounds that were once treated primarily as cultural threats are becoming some of the most intensively investigated tools in contemporary neuroscience.
There is an irony here that should not be ignored.
Indigenous people could be persecuted for maintaining relationships with psychedelic medicines.
Now Western institutions may patent derivatives of those same medicines.
Scientific progress without historical memory can easily become another form of extraction.
For decades psychiatry has asked whether depression is biological or psychological.
Psychedelic science makes the distinction increasingly difficult to maintain.
Psilocin binds to serotonin receptors. Neural signaling changes. Network organization changes. Plasticity increases. At precisely the same time, memory changes, perception changes, emotion changes, the sense of self changes, relationship becomes important, context becomes important, and meaning changes.
These are not different treatments happening to different people.
They are dimensions of the same event.
The Nature study makes this particularly clear because it demonstrates that changes in the environment are reflected in the organization of psychedelic brain activity itself. (Nature)
Biology becomes more receptive to context.
Context shapes experience.
Experience shapes learning.
Learning changes biology.
At that point, the old division between biological psychiatry and psychological therapy begins to look artificial.
I think one of the most useful ways of understanding psychedelic therapy is as a temporary window of heightened possibility.
Psilocybin does not automatically heal trauma.
It does not automatically create wisdom.
It does not automatically install a healthy self image.
Plasticity simply means the system becomes more capable of changing.
Trauma uses plasticity too.
So does attachment.
So does fear conditioning.
This is why setting, therapeutic relationship, preparation, and integration are not minor additions.
If the nervous system becomes unusually open, then what happens during that openness becomes unusually important.
The psychedelic state may temporarily reduce the authority of old predictions.
The therapist and environment can help create conditions in which another experience becomes possible.
The person may experience grief without collapsing.
Vulnerability without abandonment.
Self awareness without condemnation.
Memory without total identification.
That is where pharmacology and psychotherapy meet.
The most exciting thing about psilocybin is not that mushrooms may become another medication.
It is that psychedelics are forcing psychiatry to reconsider what treatment means.
The older pharmaceutical model tends to imagine a pathological system requiring continuous management. The psychedelic model opens another possibility: that some psychiatric suffering involves a system that has become excessively constrained, and that treatment can temporarily increase flexibility while providing the conditions for psychological reorganization.
This is not anti biology.
It is a more sophisticated biology.
The brain is not a machine with one defective chemical.
It is an adaptive prediction system that changes through experience.
It is not anti psychotherapy.
It gives psychotherapy a biological mechanism through which deeply meaningful experience can become durable learning.
It is not anti medicine.
It asks medicine to become large enough to include consciousness, relationship, environment, culture, and meaning.
Supporting psychedelic medicine does not mean pretending there are no risks. Psilocybin is a powerful psychoactive substance. People vulnerable to psychosis or mania may require exclusion or careful specialist assessment. Cardiovascular considerations matter. Psychedelic experiences can include fear, panic, confusion, nausea, grief, temporary increases in blood pressure, and psychologically overwhelming material.
But acknowledging risk is not the same thing as returning to the cultural assumption that prohibition is safer than knowledge.
Powerful interventions require rigorous research.
They require training.
They require screening.
They require informed consent.
They require ethical safeguards.
What they do not require is another generation of fear based mythology.
The growing evidence surrounding psilocybin presents psychology with an unusually hopeful possibility.
Depression may not simply be something inside the person that has gone chemically wrong.
In some people it may also involve a system that has become painfully rigid.
The same beliefs repeat.
The same predictions repeat.
The same self image repeats.
The same networks communicate in the same ways.
The person experiences this repetition as identity.
Carhart-Harris’s entropic brain hypothesis suggests that psychedelics temporarily increase the diversity and flexibility of brain activity. His REBUS model proposes that psychedelics loosen the authority of deeply weighted beliefs and predictions, allowing them to become more available for revision. His treatment resistant depression studies showed that people whose depression had persisted despite conventional treatment could improve substantially after supported psilocybin therapy. His imaging research has repeatedly linked psychedelic treatment with changes in networks involved in self processing, emotion, and cognitive flexibility. (PubMed Central (PMC))
The 2026 Nature study now adds something remarkable. The psychedelic brain is not simply becoming disorganized. Beneath the apparent entropy is a flexible organization that aligns itself with context. Music, meditation, rest, and visual experience become differently represented in neural dynamics. People who experience deeper positive dissolution of the ordinary boundary between self and environment show stronger context alignment, greater embeddedness, and greater subsequent psychological change. (Nature)
This means the environment matters.
Relationship matters.
Experience matters.
Meaning matters.
The medicine matters, but the medicine does not exist in isolation.
Indigenous psychedelic traditions understood this long before Western neuroscience could measure it.
Perhaps that is the larger lesson of the psychedelic renaissance. Western medicine spent decades asking what chemical inside the mushroom changes the brain. We are finally beginning to ask what happens when that chemical makes the brain more receptive to experience itself.
For someone who has lived twenty years believing, “This is simply who I am,” that possibility is profound.
The self may be more plastic than depression tells us.
The brain may be more capable of reorganization than psychiatry once imagined.
And the substances we spent decades treating primarily as threats may ultimately help teach us something psychology has struggled to articulate for a very long time:
We are not only what has happened to us.
We are also organisms capable of learning again.
Psilocybin remains an investigational treatment for depression in the United States and is not presently FDA approved for depressive disorders. The clinical research discussed in this article generally involves carefully screened participants receiving controlled doses with preparation, professional supervision, and psychological support. This article is educational and should not be interpreted as advice to self administer psychedelic substances.
The clinical vignette sections in this draft are placeholders, not descriptions of actual clients. Before publication, they should be replaced with genuine clinical examples used with permission and with identifying information thoroughly anonymized. All client scenarios in the published version are used by permission and identities are anonymized.
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