About Ketamine

Normal brain functions through a series of chemical reactions. In these reactions, nerve cells release chemicals called neurotransmitters that bind to receptors on other neurons, causing stimulation or inhibition. Such neurotransmitters include the monoamines dopamine (DA), norepinephrine (NE), and serotonin (SE). 

DA mediates motivation/desire, NE alertness/energy, and SE mood/sleep/memory. It used to be thought that depression is due to a deficiency of these chemicals. Thus, for years, mononamine oxidase inhibitors, tricyclic antidepressants, and serotonin/norepinephrine reuptake inhibitors were given to increase their levels. 

Unfortunately, 30% of people do not respond to the above drugs. This has led to the idea that depression may be related to other neurotransmitters, such as glutamate, the most abundant neurotransmitter. Other important findings of depression include  inflammation, loss of neurons, and abnormal circuitry/communication.

Created in 1962, ketamine is an anesthetic used control pain during surgery and procedural sedation. Its dissociative effects make patients feel disconnected from reality. Ketamine works by blocking the N-methy-D-aspartate (NMDA) receptor, a cell membrane protein to which glutamate usually binds. 

Paradoxically, by blocking NMDA receptors, ketamine  causes some neurons in the brain to produce more glutamate. This increase in glutamate stimulates another receptor, the AMPA receptor, to produce brain-derived neurotrophic factor (BDNF). BDNF then stimulates neuron growth and reconnections, reducing depression.

In addition to stimulating nerve growth and restoring neuronal circuitry, ketamine also acts on opioid/serotonin receptors and decreases the inflammation associated with depression. Ketamine's exact mechanism in treating depression remains controversial, but there is no dispute that its effects are robust and rapid.