One of the most compelling — and least understood — aspects of ketamine and esketamine (which I’ll refer to as just “ketamine” from here on out to keep it simpler) therapy lies beneath the surface of its immediate effects. While many patients describe moments of deep emotional clarity, dissociation, or relief from despair during sessions, these are just the visible tip of the iceberg. The deeper story involves something more enduring and biological: neuroplasticity – “neuroplasticity” refers to how the brain is able to produce and maintain connections called “synapses” in the brain - these synapses allow information to only be stored, but also guide how people think.
In recent years, researchers and clinicians alike have turned their attention to how ketamine and neuroplasticity intersect, increasingly recognizing ketamine’s ability to incline the brain toward creating and sustaining connections between brain cells. In this way, it opens up windows for healing that, for many patients, have long felt closed…
This post explores the science and the clinical significance of ketamine neuroplasticity — what it means, how it works, and why it matters for people living with depression, PTSD, and other mental health conditions.
What Is Neuroplasticity?
Neuroplasticity refers to the brain’s ability to reorganize itself by forming new connections (the “synapses” referred to, above) between brain cells. These connections occur naturally as different networks in the brain are developing and seeking connection and they also occur when the brain notices that two seemingly distinct phenomena happen simultaneously (coincide). Let’s take an example of learning how to read (this will be oversimplified but hopefully help make the point!): when a person sees the letter “A” and the person is taught that the letter “A” makes an “aaaa” sound, areas in the brain related to visual cortex (where visual information is processed) and areas of the brain in the auditory cortex (where sound information is processed) will “notice” that the visual phenomenon of “A” and the sound “aaa” coincide frequently and must, therefore, be related. In this simplified example, a synapse is formed connecting the physical form of the letter “A” to its anticipated sound, and, in this process, we learn through the formation of the connection that “A” makes an “aaa” sound. The connection between brain cells is the foundation for learning, memory, adaptation, and recovery. In a healthy brain, neuroplasticity allows us to adjust to new experiences, recover from injury, and build new behavioral patterns.
In the context of mental health, however, neuroplasticity can become constrained. Chronic stress, trauma, and depression are known to reduce the brain’s flexibility. Over time, the neural pathways that reinforce negative thought-loops, avoidance behaviors, or emotional numbness become more deeply entrenched — while alternative pathways weaken or and are underused. In other circumstances, information that “coincides” may not serve to help us mount a recovery. If, for example, a person with depression thinks of himself/herself/themselves and then has a negative thought about himself/herself/themselves, the brain will recognize this coincide and encode it: thoughts of self are related to thoughts of worthlessness. This association becomes hard coded and can become the automatic association that one has about oneself.This is where ketamine enters the picture.
How Does Ketamine Increase Neuroplasticity?
The question does ketamine increase neuroplasticity has been the subject of significant scientific inquiry in recent years. The answer, increasingly, appears to be yes.
Ketamine acts primarily on the glutamatergic system, particularly the NMDA receptor. Unlike traditional antidepressants, which target serotonin or norepinephrine pathways, ketamine rapidly increases glutamate levels. This cascade triggers the release of brain-derived neurotrophic factor (BDNF), a protein critical for the formation of new synapses and the strengthening of existing ones.
In short, ketamine neuroplasticity refers to this remarkable ability of ketamine to promote the creation of new synaptic connections. Animal studies show that within hours of a single ketamine dose, dendritic spines (outreachings of the brain cell that connect with other brain cells, thereby forming synapses) begin to regrow in the prefrontal cortex — an area associated with mood regulation, decision-making, and emotional resilience.
In human patients, the evidence is more indirect but no less compelling. People who experience rapid relief from depression following ketamine therapy often describe feeling more mentally agile, emotionally open, and cognitively “unstuck.” These changes are not just psychological — they’re structural. With ketamine, the brain enters a state in which forming new synapses happens more readily. It is primed to recognize and code connections. Let’s think about what this means in practice.
Ketamine and Neuroplasticity in Practice
In clinical settings, the interaction between ketamine and neuroplasticity is not just theoretical — it is therapeutic. At Lumin Health, we view ketamine as a catalyst for change. But we also recognize that this change doesn’t happen automatically. It needs structure, support, and integration.
When ketamine temporarily enhances neuroplasticity, it opens a “window of malleability” — a period of time when the brain is not only more receptive to new insights, behaviors, and emotional shifts, but also more readily encodes these new thoughts and ideas physically as synapses. This is when psychotherapy, lifestyle adjustments, and relational healing can have a deeper impact.
Consider a patient with treatment-resistant depression who has been managing in cognitive patterns of worthlessness and hopelessness for years. After a ketamine session, the emotional charge behind those beliefs may soften as ketamine directly affects mood, but it’s what happens next — how the patient reflects on that shift, talks about it in therapy, and acts on it in life — that truly rewires the brain. Challenging negative thoughts and thinking of alternative narratives can become “coded” into the brain.
An Example of How Ketamine Therapy Impacts Neuroplasticity
Let’s think about this by way of an example of a theoretical patient: Chris is a 33 year old woman who has been depressed for some time and thinks poorly of herself. Whenever she thinks of herself she automatically recalls her failings, her challenges, and her shortcomings (at the expense of thinking about her achievements, etc.). Chris decides to explore ketamine and, as part of her treatment, she sets out to notice her achievements, her strengths, and how some of the way she regards herself negatively is a distortion of the truth. As the brain is in a state to learn new things, it quickly sets up new connections between coinciding phenomena: I (Chris) (the first idea) am powerful (the second idea). These two ideas become more readily linked and the brain/mind becomes more inclined to automatically attribute a positive quality to Chris when she thinks of herself. This example is very oversimplified, but hopefully illustrates the way in which ketamine and the practice of self reflection and establishing healthy habits go hand in hand as the brain is in a state to more readily code in helpful information and daily patterns.
Clinical Timing: Making the Most of the Neuroplastic Window
Understanding that ketamine neuroplasticity is time-sensitive helps us shape the therapeutic container. The neuroplastic window often begins within hours of a session and may last several days. During this time, the brain is more flexible — more capable of absorbing new emotional and cognitive experiences.
This is why at Lumin Health, we strongly encourage integration practices: therapy sessions , journaling exercises, body-based therapies, and lifestyle changes that support new habits. With proper support and intention, subtle changes can take root and grow. We also encourage patients to reduce inputs that could undermine neuroplasticity — like heavy alcohol use, excessive screen time, or sleep deprivation.
Research Highlights on Ketamine and Neuroplasticity
Emerging studies continue to affirm the link between ketamine and neuroplasticity:
- A landmark study published in Nature demonstrated that a single dose of ketamine rapidly increased dendritic spine formation in the prefrontal cortex of rodents, with observable behavioral improvements in depressive symptoms.
- Clinical imaging studies in humans have shown increased functional connectivity between key brain regions following ketamine treatment — suggesting shifts in how different parts of the brain communicate.
- Longitudinal data suggest that repeated ketamine sessions, particularly when paired with psychotherapy, may produce sustained improvements by reinforcing these new neural patterns over time.
These findings help answer the question, does ketamine increase neuroplasticity, with growing confidence.
Limitations and Considerations
While the relationship between ketamine neuroplasticity and healing is exciting, it is not magic. Not every patient responds the same way. Some may feel no noticeable cognitive change after a session; others may have powerful insights that don’t lead to behavioral shifts. Neuroplasticity creates possibility — not inevitability.
Additionally, ketamine is not the only way to promote neuroplasticity. Physical exercise, mindfulness, sleep, enriched environments, and therapeutic relationships all contribute to the brain’s ability to change. What ketamine may do is accelerate and deepen this process, especially for patients who feel “stuck” in ways that other interventions haven’t reached.
Does Ketamine Increase Neuroplasticity?
Yes — but what really matters is what we do with that opportunity. The interplay between ketamine and neuroplasticity offers a new paradigm for mental health treatment — one grounded not just in symptom relief, but in transformation.
Ketamine neuroplasticity is not a side effect. It’s the mechanism. It’s what allows patients to move from temporary relief to lasting change. But like any growth process, it requires care, guidance, and commitment.
At Lumin Health, we believe that healing is not just about changing how people feel — it’s about changing what their brains can do. And in that work, neuroplasticity is both the path and the promise.
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