The Neuroscience of Ketamine

illustration of a neural synapse releasing glutamate

The human brain is a complex organ that is responsible for our thoughts, feelings, and behaviors. It is made up of billions of interconnected neurons that communicate with each other through synapses. Neurotransmitters, the chemical messengers of the brain, play a crucial role in this communication process.

Different neurotransmitters exist within the brain, and neurons have specific receptors for each of them. The activation of these receptors allows charged ions to flow into neurons, facilitating signal transmission between them. In this blog post, we’ll dive into the role of neurotransmitters and receptors, the positive impact ketamine has on neurotransmitters and ketamine’s potential for relieving the symptoms of many mental health conditions.

Neurons, Neurotransmitters & Receptors


The brain is composed of billions of cells called neurons. Synapses are the connections between neurons or the space between neurons that allows one to pass a signal to another. Neurons communicate using chemicals called neurotransmitters. There are many different kinds of neurotransmitters. Neurons have receptors that only recognize specific ones. Without the corresponding receptor, the neuron will be unaffected by the neurotransmitter’s release.

Neurotransmitters find the right receptor by random collision. The greater the amount of neurotransmitter passing a receptor, the greater the chance of the receptor being activated. At a synapse, activation of the receptor opens a channel for the flow of charged ions inside the neuron. When enough positively-charged ions have flowed into a neuron, it will spike and release its own neurotransmitter.

Ketamine and Glutamate Receptors


Ketamine acts on a wide range of brain receptors. At low doses, it is most likely to affect a family of glutamate receptors called NMDA receptors (located in your limbic system, which is responsible for learning, memory, and emotional regulation). After glutamate has activated the NMDA receptor, it opens a channel for the flow of positively-charged ions. Ketamine blocks the channel, preventing the neuron from being excited. Now, instead of exciting a neuron, a neurotransmitter may be inhibitory. It opens channels for negatively-charged ions, making the neuron less likely to spike. NMDA receptors are found on a lot of neurons that release inhibitory neurotransmitters. By interfering with the excitement of these neurons, ketamine has the counterintuitive effect of increasing neuronal activity.

Ketamine’s Effect on Brain Function


Ketamine exerts various effects on brain receptors. Specifically, therapeutic doses target NMDA receptors, which are responsible for learning, memory, and emotional regulation. Studies have demonstrated that ketamine acts as an NMDA receptor antagonist, influencing synaptic transmission and leading to its antidepressant effects. Research published in The Journal of Neuroscience revealed that ketamine’s interaction with these receptors can provide rapid relief to patients suffering from treatment-resistant depression (TRD).

Another study published in The Frontiers of Cellular Neuroscience found that ketamine enhances synaptic plasticity and increases brain-derived neurotrophic factor (BDNF) expression, providing insight into the potential therapeutic mechanisms of ketamine. Brain-derived neurotrophic factor (BDNF) plays a vital role in promoting the growth and repair of neurons and synapses. Chronic stress can reduce BDNF levels, contributing to mental health conditions like depression and anxiety. Findings such as those offered by The Frontiers of Cellular Neuroscience establish ketamine as a promising tool for the treatment of many mental health conditions due to its targeted impact on brain receptors and neural pathways.

Why is Ketamine-Assisted Therapy Effective?


While Ketamine has undoubtedly proven to have a positive effect on the brain, ketamine-assisted therapy with integration therapy by properly trained therapists/guides provides for more sustained results. From a neurological perspective, one of ketamine’s positive impacts on the brain is its blocking of inhibitory neurotransmitters, leading to increased glutamate transmission. This, in turn, triggers a rise in brain-derived neurotrophic factor (BDNF) levels. The ability of ketamine to restore BDNF levels is, in large part, responsible for its efficacy. Studies support the claim that IV ketamine therapy increases glutamate levels in the prefrontal cortex, and this increase correlated with rapid antidepressant effects.

Glutamate is the most abundant neurotransmitter in the brain and plays a crucial role in neuroplasticity. By increasing glutamate levels, ketamine can promote the growth and survival of neurons through the activation of BDNF. Additional studies prove ketamine-assisted therapy leads to increased levels of BDNF in patients with treatment-resistant depression, further supporting its function in neuroplasticity and treatment efficacy. It is ketamine’s blockade of NMDA receptors that promote the release of other neurotransmitters, such as dopamine and serotonin, which assist in mood regulation. Furthermore, ketamine enhances fear discrimination and fear extinction learning based on BDNF signaling. It is this mechanism that we see the success of ketamine-assisted therapy in patients struggling with anxiety, trauma, and PTSD.

How to Leverage This Knowledge


The neuroscience of ketamine therapy is a fascinating field of research that holds immense promise for revolutionizing mental health treatment. The evidence from various studies supports ketamine’s impact on brain function, mainly through its interaction with NMDA receptors, the modulation of neurotransmitter levels, and the promotion of BDNF expression. With ongoing research, we stand on the brink of unlocking the full potential of ketamine as a game-changer in mental health care.


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