There is much debate on how ketamine works as an antidepressant. The most accepted theory is that it inhibits glutamate (a neurotransmitter, not in the monoamine family) via the NMDA receptor. But, like most things, it’s not so simple.
As mentioned earlier, ketamine has many different functions in the brain, not least of which is creating an altered state wherein the individual may have a transformative experience with new insights and perspective shifts.
Remember, ketamine is a dissociative anesthetic. Dissociating from what, you may ask? In simple terms: your thoughts from your emotions. As one scientist explains (paraphrasing) ‘when on ketamine, you may have negative emotions, but you don’t care.’ That’s a rather glib way of saying: ketamine offers you space from your emotions.
Because it dissociates part of the limbic system from the cortex, it allows you to experience unpleasant memories or feelings without being triggered by them. This means you can do deep KETAMINE 101 | Dr. Katelyn Kalstein | Evolve Healthcare | Woodland Hills, CA | (818) 346-4300 4 psychological work without your ego defenses getting in the way. The effect of this makes one feel as if they’ve done “5 years of therapy in 5 hours.”
Anatomically, it is clear that ketamine reconnects neurons. Neuroscientists performing functional MRIs while patients are on ketamine see an increase in the functional connectivity of neurons. We know that depressed patients have fewer connections, so it follows that with more connections, you have less depression.