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The Science Of Treating Depression With Ketamine

The Science Of Treating Depression With Ketamine

The Science Of Treating Depression With Ketamine



Ketamine or “K” is a dissociative anaesthetic drug used in a variety of clinical settings, from veterinary clinics to the battlefield and hospital emergency rooms. It is on the World Health Organization’s Essential drug list and highly safe for clinical use because it anaesthetizes patients without threatening their airways and other vital nervous system functions, and it is even used regularly on children2.

K is also widely used recreationally for its psychedelic effects at sub-anaesthetic or even fully anaesthetic doses. The latter is often called a “K-hole”, the peak psychedelic experience of a ketamine trip. There are many interesting concepts surrounding the experiential topography of K, which I will not be discussing here. There is also an addictive potential for ketamine in its recreational use, but less than other substances such as nicotine, cocaine, opiates, and alcohol.

K has found other uses over the last fifty years, such as a potential treatment of chronic pain disorders5 and what this article intends to demystify, is its use as a fast acting anti-depressant.

Ketamine For Depression

The potential of these anti-depressant effects are remarkable; a single session with K can help reduce symptoms in treatment-resistant depression, bipolar disorder, and acute suicidality for up to a week1,4. It has also been shown to offer noticeable reduction in symptoms of both obsessive-compulsive disorder and post-traumatic stress disorder4. What is most interesting is that these effects come on within about two hours of onset and depending on dose and duration of administration, can last for up to a week, long after the drug has be metabolized and removed from the system3. Whereas our other medications for treating depression—assuming it can be chemically treated at all—take several weeks of regular use to take effect, such is the case with Selective Serotonin Reuptake Inhibitors or SSRIs1.


Source: Wikipedia

The basic action of ketamine’s immediate effect is on the glutamate neurotransmitter system, wherein it binds to a very specific dock on the NMDA receptors (this dock also binds PCP), blocking the uptake of glutamate3. In that way, its actions are similar to Magnesium, leading to insight about magnesium deficiency and supplementation in the management of depression10. Glutamate is the major excitatory transmitter in the brain and thus effectively cuts off “go” signals between the brain and the body (anaesthetic). Yet it also has both positive and negative effects on other neurotransmitter systems such as dopamine, acetylcholine, and the opioid system, contributing to its psychoactive effect beyond sedation3.

K’s delayed effects are what seem to be playing a role in its anti-depressive actions. Ketamine seems to increase production of Brain Derived Neurotropic Factor (BDNF)1,2,3,4, and the mammalian target of rapamycin (mTOR) in the hippocampus and the medial prefrontal cortex (mPFC)2,3,4.

BDNF is a brain protein that helps with the production of new and protection of old neurons and synapses as well as adaptability to mood and emotions1,4,9. mTOR is also a protein responsible for various functions relating to cell growth and survival8. The hippocampus is a part in the brain involved in learning and memory7. The mPFC is thought to be an area responsible for planning complex cognitive behaviors, such as working towards goals and determining ‘good and bad’6. What is interesting here is that long-term depression actually reduces BDNF and mTOR in the hippocampus and mPFC1,4. It also causes changes to those areas in the brain, specifically decreased neural connectivity1,4,16.

A long-term effect of taking SSRIs is an increase in BDNF1. This observation along with the neurophysiological pathology of depression and the effects of ketamine lead to conjecture that drugs like SSRIs actually work to improve depressive symptoms via their direct effect on serotonin, by their ability to mitigate stress while the brain increases BDNF and mTOR again, or by directly increasing BDNF themselves


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(Articolo pubblicato dal CUFRAD sul sito www.alcolnews.it)