How it Works

There are three major receptors in your brain that are responsible for antidepressant properties and moreover, your general maintenance of mood. Two receptors, known as the NMDA and AMPA receptors are widely thought to be most responsible for managing mood, while the third, the opioid receptor group, is responsible for pain control. All three of these receptors are activated by ketamine.

In the body, ketamine is broken down into two metabolites called R-ketamine and S-ketamine. These two metabolites exist at equal levels in the body and both serve to activate the NMDA, AMPA, and opioid receptors. It is through the interaction of these two metabolites with these receptors that ketamine can influence a person’s mood.

How it Works
So how do these receptors treat depression? Because of the activation by these receptors, pathways in your brain that are responsible for depression are, in a sense, repaired. A study published by Behavioral Pharmacology showed that following ketamine infusion treatment, patients’ brains showed greater activation in brain areas that are responsible for controlling depression1. Further, the same study shows that areas of the brain are better connected to each other for sustained periods of time following ketamine treatment. This implies that ketamine works to maintain pathways in your brain that prolong antidepressant properties over time.
Citations

  • Maltbie, E. A., Kaundinya, G. S., & Howell, L. L. (2017). Ketamine and pharmacological imaging: use of functional magnetic resonance imaging to evaluate mechanisms of action. Behavioural pharmacology, 28(8), 610–622. https://doi.org/10.1097/FBP.0000000000000354
  • McCloud TL, Caddy C, Jochim J, et al. Ketamine and other glutamate receptor modulators for depression in bipolar disorder in adults. Cochrane Database Syst Rev. 2015;(9):CD011611. Published 2015 Sep 29. doi:10.1002/14651858.CD011611.pub2

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