How Ketamine-Assisted Therapy Changes the Brain: Neuroplasticity, Inflammation, and Mental Health Explained
By Nadia Scurfield
Why Understanding Ketamine-Assisted Therapy Reduces Fear
Fear often grows in the absence of understanding.
When something is unfamiliar, especially in the realm of mental health, it is easy for caution to turn into avoidance. Yet meaningful progress rarely happens through silence or stigma. Real change happens through education, thoughtful dialogue, and open minds.
Many treatments carry both risks and benefits. Ketamine-assisted therapy (KAT) is no exception. What’s often missing from the conversation, though, is context. When used in a legal, insured, and medically supervised therapeutic setting, KAT is very different from the version many people imagine. Much of the fear surrounding it comes not from evidence, but from misunderstanding.
By exploring the science behind KAT, how it interacts with the brain, and the ways it supports mental health, we can move from fear toward informed choice. This overview is an invitation to learn, so you can decide whether KAT feels like a path worth exploring for you.
How Ketamine-Assisted Therapy Works in the Brain
Neuroplasticity: Rewiring Depressive Thought Patterns
When Ketamine reaches the brain, it sets off a powerful chain reaction. It binds to neuronal receptors, which triggers a surge of glutamate, an excitatory neurotransmitter involved in learning, adaptability, and memory. This glutamate leads to an increase in neuronal growth factors (NGFs). Think of these NGFs as fertilizer for neurons that allows brain cells to develop, grow, and survive*.
So, what does this mean for your mental health?
Essentially, ketamine drives a cascade of events which allows the brain’s cells to grow and change*. This is known as neuroplasticity— the brain’s ability to form new connections and reorganize existing ones. Neuroplasticity is essential for healing, especially when the brain has been shaped by chronic stress, trauma and long-term depression.
The impact of KAT can actually be seen through changes in brain activity. Following KAT, activity can become normalized—or, more similar to typical patterns—in regions of the brain associated with mood disorders. These include the hippocampus (the memory centre) and the prefrontal cortex (the personality centre).
By driving targeted change, Ketamine can disrupt entrenched pathways such as negative thought patterns, while supporting the architecture of new pathways, allowing clients to access new perspectives, insights, and emotional responses, and break free from cycles of negative beliefs.
2. Anti-Inflammatory Effects and Depression
Chronic stress doesn’t just change how you feel emotionally; it also takes its toll on the physical body. This can be seen by an increase in inflammation*, the body’s natural immune response that is designed to protect and heal, but becomes harmful when it stays switched on for too long. What may be surprising is the fact that this phenomenon can, in turn, take a toll on the brain.
Inflammation within the brain can greatly impact the delicate balance of brain chemicals that regulate mood, motivation, and emotional resilience. Research suggests that in cases of depression, particularly in treatment-resistant forms, brain inflammation plays a role in both developing and maintaining symptoms*.
Ketamine appears to intervene in this process. When ketamine reaches the brain, it can signal inflammatory activity to calm down, helping reduce the release of certain inflammatory chemicals. By interrupting this inflammatory loop, ketamine may support antidepressant effects, creating a more stable internal environment where healing and recovery can begin*.
3. Increased Brain Entropy and Mental Flexibility
Entropy is the degree of randomness, or disorder, within your brain at a given moment. As such, it describes how rigid or flexible your brain is. Low entropy is associated with high levels of organization and the brain operating in an orderly, predictable way. While structure can be helpful, too much rigidity can cause difficulties. In depression, low entropy is thought to contribute to the mind being locked on negative thoughts, behaviours and beliefs*.
Ketamine may be able to increase entropy within the brain* by introducing an element of randomness to thought patterns. In other words, it introduces a degree of openness and variability into how thoughts and perceptions are experienced.
By increasing randomness and mental flexibility, your brain can shift into a state that is more conducive to adaptation and rewiring of neuronal connectivity. This temporary disruption of entrenched, negative thinking can create space for new insights, emotional shifts, and alternative ways of relating to experiences — making it easier to move beyond patterns that no longer serve.
4. The Subjective Experience of Ketamine-Assisted Therapy
Research shows that Ketamine may give rise to powerful inner experiences that include feelings of connection, openness, hope and a sense of oneness. While these experiences are deeply personal and profound, these feelings have been linked to ketamine’s effects on the key brain chemical glutamate*.
Glutamate is an excitatory neurotransmitter and activates regions of the brain critical for perception, awareness, and emotional processing. Under ketamine, areas of the brain linked to these functions can become activated even without external stimulation. This is why some people may experience altered perceptions, vivid imagery, or changes in how sound, space, or time are felt.
Subjective, positive experiences can play an important role in KAT as they open your mind to new perspectives. Moments of expanded awareness or emotional openness may help soften rigid self-stories and create distance from long-held negative beliefs. Looking through this new lens may allow a better understanding of self and the disentanglement of identity from negative beliefs.
Who Is Ketamine-Assisted Therapy For?
By supporting physical shifts in your brain, KAT may have the potential to change how one experiences oneself and the world around them. For those who have felt stuck in familiar patterns for too long, this openness can create meaningful momentum toward healing.
If you’re curious to learn more, we invite you to book a Discovery Call. This is a space to ask questions, explore the program, and see if it aligns with where you are right now.
References:
https://pmc.ncbi.nlm.nih.gov/articles/PMC8653702/
By Nadia Scurfield
Nadia Scurfield is a fourth-year Neuroscience major at the University of British Columbia. Focusing on the Behavioural and Cognitive stream, she is passionate about understanding the brain’s inner workings - especially in the context of mental health.
At Qi, Nadia works as a member of the Patient Services Team. Outside of work, she volunteers as a research assistant within two UBC labs and is working towards applying to Graduate Degrees in Clinical Psychology.
