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How It Works

How Does Ketamine Infusion Therapy Work For Mood Disorders?

Ketamine is an NMDA receptor antagonist and an AMPA receptor stimulator. AMPA stimulation results in increases in BDNF (brain-derived neurotrophic factor). BDNF stimulates the formation of new receptors and synapses (which are vital connections between neurons). Research suggests that a deficiency in these connections is associated with the major depressive disorder and other mood disorders, difficulties with sleep, and focus.

One of the brain’s key neurotransmitters is glutamate, an amino acid found in 80% of neurons. Glutamate influences the formation and number of brain synapses, the vital connections between neurons. Glutamate acts with another important neurotransmitter, GABA, to maintain a healthy, well-functioning nervous system. An imbalance between GABA and glutamate can cause problems, including anxiety, difficulties sleeping, and issues with focus. Imbalance in the glutamatergic system is also associated with the major depressive disorder (MDD). Growing evidence suggests that ketamine helps rebalance the glutamate system by acting as a receptor antagonist. One of the ways ketamine works is by blocking the NMDA (N-methyl-D-aspartate) receptor, one of three major glutamate receptors. This receptor is involved in synaptic plasticity and memory function, among other functions. A ketamine-induced blockade of the NMDA receptor results in an increase in glutamate. This initiates a cascade of neurobiological events that researchers believe is one key reason behind ketamine’s rapid antidepressant effects. In layman’s terms ketamine indirectly stimulates the formation of new receptors and synapses which reconnect neurons in the brain for normal brain function.

How Does Ketamine Infusion Therapy Work For Pain Relief?

With Complex Regional Pain Syndrome (CRPS/RSD) and other chronic pain, a process known as central sensitization is thought to intensify pain by increasing the number of NMDA receptors thus amplifying the pain signal. Ketamine’s interference with the NMDA receptor is thought to block and reset pain signaling, providing relief where other treatments have failed. By blocking the NMDA receptors of peripheral nerves, peripheral nerve pain transmission is intercepted before reaching the spinal cord and brain. This allows for rebooting of central pain centers and desensitization to peripheral pain signals.

Ketamine

Ketamine Molecule

How Ketamine Works

The proposed mechanism of ketamine’s antidepressant action, whereby ketamine, through a blockade of tonic GABAergic inhibition (1), causes a surge in glutamate release and cycling (2). The resulting increased glutamatergic transmission through AMPA receptors (whose surface expression may be independently upregulated by the suppression of spontaneous NMDAR-mediated neurotransmission) (3) leads to increased BDNF-dependent (4) levels of synaptogenesis (5) that ultimately contribute to the rapid and sustained antidepressant effects.

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