Is 'entropy' a good thing for the brain?

In moderation. Too much entropy looks like psychosis or severe disorganization; too little looks like rigid, ruminative depression. The therapeutic idea behind the Carhart-Harris framework is brief, controlled increases in signal diversity that give the brain a chance to settle into healthier patterns afterward. It is the change, not the high entropy itself, that may matter.

Is this the same as the 'reset' people talk about with psychedelics?

Loosely, yes. The 'reset' metaphor is shorthand for the entropy and network-loosening idea. Both are still working hypotheses, not proven mechanisms. The molecular story for ketamine, AMPA activation and BDNF release, is more established than the entropy framing, which sits a level higher and tries to explain what those molecular changes do at the network scale.

Will I experience increased brain entropy as something specific during a session?

Many patients describe it as the sense of being able to think differently. Old loops feel less sticky. Familiar problems feel less fixed. The subjective experience varies a lot from person to person, and not everyone who responds clinically reports an obvious shift in the moment. The day-after sense of mental flexibility is what most patients notice.

Is brain entropy the reason ketamine works for depression?

Possibly part of it. The molecular story, AMPA throughput, BDNF, mTOR, and synaptic regrowth, is more established as the mechanism. Entropy is a higher-level framing that may complement the molecular work by describing what changes at the network level. Research suggests both stories are pointing at the same phenomenon from different angles, but the picture is not settled.

Does Spravato produce the same entropy increase as IV ketamine?

Direct esketamine entropy studies are limited. The mechanism family is similar, both act on the NMDA receptor system, so a similar effect is plausible. We would not quote it as established. If you are weighing IV racemic ketamine against intranasal Spravato, the entropy framing is not strong enough on its own to drive that decision. Talk to your prescribing provider about which makes sense for you.

Ketamine and Brain Entropy: The Carhart-Harris Framework, in Plain English

What “brain entropy” actually means

Entropy, in this context, is borrowed from information theory. It is a measure of how diverse, unpredictable, or rich a signal is. A perfectly regular metronome has very low entropy. A jazz improvisation has higher entropy. A room full of static has the highest entropy of all. The brain sits somewhere on that spectrum, and it does not stay still. Different states of consciousness sit at different points.

When researchers talk about “brain entropy,” they usually mean the moment-to-moment diversity of neural signals measured with EEG, MEG, or fMRI. Higher entropy means the brain is producing a wider range of patterns. Lower entropy means it is settling into a smaller set of repeated configurations. Neither extreme is healthy. The interesting region is the middle, where the brain has enough structure to function and enough flexibility to adapt.

This framing matters because depression, anxiety, OCD, and chronic-pain syndromes share a common phenomenology: the mind gets stuck. The same thoughts return. The same fears repeat. The same body sensations dominate. If the underlying neural dynamics are also more rigid, then a treatment that briefly loosens those dynamics has a logical place to act.

Carhart-Harris’s entropic brain hypothesis

The original paper is Carhart-Harris and colleagues, “The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs,” published in Frontiers in Human Neuroscience in 2014. It proposed that primary states of consciousness, including those induced by classic psychedelics, are characterized by elevated entropy in functional brain dynamics. Ordinary waking consciousness, by contrast, is a more constrained, lower-entropy state.

The clinically interesting part of the hypothesis is what it implies for rigid pathological states. If depression, addiction, and obsessional thinking represent the brain getting stuck in over-trained patterns, then briefly raising entropy might be therapeutic, not because high entropy is good in itself, but because it gives the system a chance to reorganize. Carhart-Harris later updated this framing in “The entropic brain — revisited,” published in Neuropharmacology in 2018, incorporating ketamine data and refining the link to therapeutic effects.

It is worth saying clearly: this is a hypothesis, not a settled mechanism. It is a useful organizing idea that lines up with a growing body of imaging data. It is not a guarantee that any particular patient will benefit. We treat it the same way we treat the molecular story — useful for understanding what the medicine is doing, not a substitute for clinical judgment.

Why rigid brain patterns might map to depression

If you ask a person in a depressive episode to describe their inner life, you will often hear the language of stuckness. The same self-critical thoughts. The same hopeless conclusions. The same loop, day after day. Cognitive science has a name for this — rumination — and rumination is one of the strongest predictors of depressive relapse.

At the network level, depression has been associated with increased connectivity and reduced flexibility in the default-mode network, the set of midline brain regions most active during self-referential thought. The default-mode network is, roughly speaking, the substrate of the inner narrator. When it dominates, the narrator gets louder. When it loosens, the narrator quiets down.

The entropic-brain framing connects these observations. A brain that has settled too deeply into its default-mode patterns is, in entropy terms, a low-entropy brain. The same dynamics that feel like rumination from the inside look like reduced signal diversity from the outside. Whether this is cause, effect, or both is still being worked out, but the convergence between subjective report and neural data is striking.

For a deeper read on the underlying biology, our piece on how ketamine works walks through the molecular layer, and our overview of ketamine brain research covers the imaging side in more detail.

Schartner 2017 and the MEG data on ketamine and psychedelics

The most direct evidence for the entropy framing in ketamine specifically comes from a 2017 study in Scientific Reports by Schartner, Carhart-Harris, and colleagues. The team used magnetoencephalography (MEG) — a technique that captures the brain’s magnetic fields with millisecond resolution — to measure spontaneous signal diversity in healthy volunteers under three different drugs: subanesthetic ketamine, LSD, and psilocybin.

The headline finding: spontaneous MEG signal diversity was reliably elevated under all three drugs compared to placebo. The increase held up after the researchers controlled for spectral changes, which is important because it means the effect was not just an artifact of altered brain rhythms. It was a genuine increase in the moment-to-moment richness of brain activity.

This was the first time signal diversity had been shown to consistently exceed normal waking levels under a psychoactive drug. The fact that ketamine produced a similar effect to classic psychedelics, despite working through a different primary receptor (NMDA versus serotonin 2A), is part of why the entropy framing has stayed interesting. It suggests a final common pathway at the network level, even when the molecular entry points differ.

Convergent evidence comes from earlier work by Scheidegger and colleagues, published in PLOS One in 2012, which found reduced default-mode network connectivity twenty-four hours after a sub-anesthetic ketamine infusion in healthy volunteers. That result lines up with the entropy framework’s prediction that ketamine loosens organized network dynamics.

How this fits with default-mode network findings

The default-mode network story and the entropy story are not competing theories. They are two views of the same phenomenon. When the default-mode network loosens its grip, signal diversity goes up. When signal diversity goes up, the default-mode network is, by definition, less dominant. The two measures move together.

This matters clinically because the loosening appears to outlast the acute drug effect. The Scheidegger data showed altered connectivity at twenty-four hours, well after the ketamine itself had cleared. That window of altered network state overlaps with what some researchers call the neuroplastic window — the period after an infusion when synaptic regrowth and learning appear elevated. A loosened, higher-entropy brain may be a more receptive brain.

This is part of why integration work, therapy, and lifestyle changes in the days after an infusion are emphasized at most reputable clinics. The drug opens a window. What the patient does inside that window may shape what the brain settles into next. We discuss this more in our piece on the ketamine neuroplastic window.

What’s hypothesis vs. what’s established

To be straightforward about the state of the evidence: the molecular story for ketamine’s antidepressant effect, NMDA blockade, AMPA throughput, BDNF release, mTOR activation, and rapid synaptic regrowth, is well established in animal models and increasingly supported in humans. Ketamine is FDA-approved as an anesthetic; its use for depression and other mood and pain conditions is off-label, with esketamine (Spravato) being the FDA-approved exception for treatment-resistant depression and MDD with acute suicidal ideation.

The entropy framing sits one level up. It is a network-level account that tries to describe what the molecular changes do at the scale of whole-brain dynamics. The Schartner 2017 MEG data and the Carhart-Harris 2018 update give it real empirical grounding. It is not a fringe idea. But it is also not a settled mechanism. Researchers are still arguing about which entropy measures matter most, how they relate to subjective experience, and whether the framework will hold up as larger studies arrive.

What we tell patients: the entropy story is a useful way to understand what your brain may be doing during and after an infusion. It is not a promise. The clinical evidence for ketamine’s effect on depression rests on randomized trials of mood outcomes, not on entropy measurements. Studies indicate ketamine may help where other treatments have not, but individual response varies, and we do not predict outcomes from any imaging or theoretical framework.

What patients describe — and what we tell them

The most common phrase we hear, in some form, after a successful series is that the old loops feel less sticky. Patients describe being able to think about a difficult subject without falling into the same conclusion. They describe noticing rumination as it starts and being able to step out of it. They describe a kind of mental flexibility that had been missing for a long time.

This subjective report lines up with the entropy framing in a way that is hard to dismiss, even if the mechanism is not proven. People who feel less stuck after treatment often describe their inner life in language that matches what higher signal diversity would predict from the outside.

What we do not promise: a specific experience during the infusion, a particular outcome, or that any imaging result will mean anything for your case. The dissociative experience during a session varies enormously, and what an infusion actually feels like ranges from gently dreamlike to vividly altered. Neither end of that range predicts who will respond clinically.

If you are exploring ketamine for depression and want a fuller picture of how the treatment is structured, those pages are good starting points. The honest answer about brain entropy is that it is a compelling, hypothesis-level framing for what may be happening at the network scale. Marla Peterson, CRNA, is in the room and oversees every infusion at Music City Ketamine, with anesthesia-level monitoring throughout. Sessions are $475 each, and we are direct about costs and expectations from the first conversation.