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What Impact Does Ketamine Have on the Brain?

As an integrative psychiatrist, I have witnessed the transformative power of ketamine therapy in treating various mental health conditions such as depression, anxiety, PTSD, and more. Unlike traditional psychiatric medications, ketamine works through unique mechanisms in the brain to provide rapid and lasting relief.

In this blog post, we will explore what ketamine does to your brain, focusing on the default mode network (DMN), brain-derived neurotrophic factor (BDNF) and neuroplasticity, and the role of glutamate.

Ketamine and the Default Mode Network (DMN)

The default mode network (DMN) is a group of interconnected brain regions that are active when the mind is at rest or engaged in self-referential thinking. Overactivity of the DMN has been implicated in various mental health disorders, including depression and anxiety.

Ketamine has been found to temporarily "reset" the DMN, allowing for increased connectivity between brain regions that are usually segregated (Carhart-Harris et al., 2016). This disruption of the DMN's overactivity leads to a reorganization of neural networks and enhanced communication between different areas of the brain.

Interestingly, other psychedelic medicines, such as psilocybin (found in magic mushrooms) and LSD, have also been observed to induce similar effects on the DMN and promote increased brain connectivity (Carhart-Harris et al., 2017; Preller et al., 2019). This shared ability to modulate the DMN and enhance brain network connectivity is thought to contribute to the therapeutic potential of these substances in treating various mental health disorders, including depression, anxiety, and PTSD, by facilitating profound shifts in perspective, self-awareness, and emotional processing.

This change in brain connectivity can lead to profound shifts in perspective, self-awareness, and emotional processing, contributing to the therapeutic benefits of ketamine.

BDNF, Neuroplasticity, and Ketamine

Another critical aspect of ketamine's impact on the brain is its ability to increase the production of brain-derived neurotrophic factor (BDNF). BDNF is often referred to as "Miracle-Gro" for the brain because of its remarkable ability to support and enhance the growth, development, and maintenance of brain cells.

BDNF is a protein that plays a vital role in the survival, differentiation, and growth of neurons, as well as in the formation and strengthening of synapses – the connections between neurons that facilitate communication within the brain.

Like Miracle-Gro, which provides essential nutrients to plants, enabling them to grow and thrive, BDNF nourishes neurons and supports their development. This, in turn, allows the brain to remain adaptable, resilient, and capable of learning and retaining new information throughout life. BDNF has also been linked to improved cognitive function, memory, and mood regulation.

Ketamine has been shown to rapidly increase BDNF levels, promoting the growth and strengthening of new neural connections (Duman et al., 2016). This enhanced neuroplasticity allows the brain to "rewire" itself, potentially leading to lasting improvements in mood, cognition, and overall mental health.

The Role of Glutamate in Ketamine's Mechanism of Action

Unlike traditional psychiatric medications, which often target the serotonin or dopamine systems, ketamine primarily works by modulating the glutamate neurotransmitter system. Glutamate is the most abundant excitatory neurotransmitter in the brain and plays a significant role in synaptic plasticity and neuronal communication.

Ketamine acts as an NMDA receptor antagonist, temporarily blocking the activity of glutamate at this specific receptor site. This blockade leads to a cascade of downstream effects, including increased release of glutamate, activation of AMPA receptors, and the previously mentioned increase in BDNF levels (Zanos et al., 2018). These changes contribute to ketamine's rapid and robust antidepressant effects.

Ketamine: A Unique Window of Neuroplasticity

Ketamine therapy creates a unique window of enhanced neuroplasticity, offering an opportunity for individuals to reshape their thought patterns and emotional responses. This window typically lasts for several days to a few weeks following a ketamine treatment, providing a crucial period for therapeutic interventions such as psychotherapy, mindfulness practices, and lifestyle changes to be integrated and solidified.

Ketamine's impact on the brain sets it apart from traditional psychiatric medications, offering rapid and lasting relief for various mental health conditions. By modulating the default mode network, increasing BDNF levels and neuroplasticity, and targeting the glutamate system, ketamine provides a unique and powerful therapeutic approach. As an integrative psychiatrist, I am continually humbled by the potential of ketamine therapy and its ability to transform lives.

If you're interested in exploring the potential benefits of ketamine-assisted therapy for yourself or a loved one, I invite you to learn more about my practice, Driftless Integrative Psychiatry. We offer personalized, compassionate care that combines the latest research and evidence-based practices with a holistic understanding of mental health. To start your journey towards healing and well-being, visit our website and schedule a consultation today.


Carhart-Harris, R. L., et al. (2016). Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of

Collingridge, G. L., Lee, Y., Bortolotto, Z. A., & Lodge, D. (2021). Antidepressant actions of ketamine: From molecular mechanisms to clinical practice. Progress in Neurobiology, 197, 101892.

Duman, R. S., Aghajanian, G. K., Sanacora, G., & Krystal, J. H. (2016). Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants. Nature Medicine, 22(3), 238-249.

Zanos, P., Moaddel, R., Morris, P. J., Georgiou, P., Fischell, J., Elmer, G. I., ... & Zarate, C. A. (2018). NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature, 533(7604), 481-486.

Preller, K. H., et al. (2019). Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor. eLife, 8, e35082.

Vasavada, M. M., Loureiro, J., Kubicki, A., Kubicki, M., & Deckersbach, T. (2021). The role of glutamate and GABA in cognitive dysfunction in major depression and potential therapeutic interventions. Frontiers in Psychiatry, 12, 618574.

Wilkinson, S. T., & Sanacora, G. (2021). Ketamine: A promising novel therapy for anxiety and PTSD. Focus, 19(1), 13-16.


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