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The Neuroscience of Ketamine

illustration of a neural synapse releasing glutamate

What really goes on in the brain when a patient undergoes ketamine therapy? Read on to find out.

Brains 101

First, let’s talk about how brains work. 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.

Neurotransmitters & Receptors

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. But only when delivered at sub-anesthetic doses.

Ketamine’s Effect on Brain Function

So why does ketamine have a positive effect on disorders like depression? By blocking the release of inhibitory neurotransmitters, and increasing neuronal activity, glutamate transmission actually goes up.
It has been proposed that this increase indirectly leads to an increase in the release of brain-derived neurotrophic factor (BDNF). BDNF is a protein that encourages the growth and repair of neurons and synapses.
Chronic stress can decrease the levels of BDNF in the brain, contributing to depression. Ketamine can reverse its effects by restoring those levels.

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