The Therapeutic Potential of Ketamine

Greg Thorkelson, MD with Ryan Reagan, PhD(c), LPC

If you have not read the previous post on the Nexus mental health blog, it might best to start there since this post will be referencing it.  We are going to spend a bit more time focusing on ketamine which has unique place in the category of agents with “psychedelic properties.”  Ketamine is unique in a couple of respects.  One, it is widely used as an anesthetic.  Ketamine was originally identified as a derivative of phencyclidine (PCP).  As an anesthetic ketamine is widely used in veterinary medicine.  It is used with children and has historically been carried in combat because of its ease in administration and safety profile.

Interestingly, the psychedelic properties of ketamine were largely looked at as an adverse or undesirable side effect.  At certain dosages, ketamine causes dissociative effects, meaning there is an experience some describe as “out of body.”  It is altogether understandable that this would be regarded as an unwanted byproduct in an anesthetic.  Most people are not looking to experience dissociation and could find such an experience frightening and disturbing.  However, this is a property that might be desirable as a psychedelic.  Much of the current research on psychedelic medication is focused on treatment resistant conditions.  Dissociation happens to be a common symptom in chronic PTSD.

The other area drawing the attention of researchers is the therapeutic use of ketamine for treatment resistant depression.  This area has expanded rapidly, and this has raised some concern amongst mental health professionals.  This is one of those instances where the science is still accumulating and being outpaced by the reality of it being readily available.  Recall, ketamine has been FDA approved for anesthetic purposes for decades.  The psychotropic effects have only recently been realized. “Recently” is being used in scientific terms, meaning the past 20 years, science is a slow process.

The good news: ketamine appears to have the ability to rapidly alleviate depressive symptoms, sometimes within hours.  The bad news: some of the research indicates that these gains are not maintained.  Unfortunately, there are also concerns about repeated and prolonged use of ketamine because of the effect of its anesthetic properties on the brain.  Furthermore, ketamine’s effects show variability depending on how it is administered—orally, intravenous (infusion), intramuscular (injection).  At this time, it is unclear what methods and what doses are best suited to which conditions and which patients may benefit.  

That is a lot of uncertainty.  What we do know is that it offers relief from symptoms in a way that we do not fully understand, and that the alleviation proceeds rapidly.  Neuroscience research indicates that the NMDA receptor and the neurotransmitters glutamate and GABA may be involved.  We are mentioning this specifically because the approach to depression treatment thus far has been predominately SSRI’s which act on serotonin.  One of the other interesting qualities is that ketamine may also stimulate the production of brain derived neurotrophic factor (BDNF).  BDNF serves in a number of important functions including neuroplasticity, regulation of neurotransmitters, and neural growth (Bathina & Das, 2015).  

The bottom line to all of this: ketamine is providing relief to chronic symptomology in a handful of conditions that have failed to achieve remission.  We do not know enough to perfectly predict responses, but ketamine is both reliable and highly safe when used appropriately.  There is also the benefit that it may be less intense than some of the other psychedelics.  It is much easier for a physician to measure and adjust dosages than something like psilocybin or LSD which appear to be much more potent.  Furthermore, the ketamine process from start to finish is fairly quick, relative to some of the more potent psychedelics that can range from 6-20 hours.

There is a fascinating question here for researchers (if that’s your thing!).  Psychedelic experiences appear to show some similarity with intensely spiritual experiences (mystical encounters).  Individuals who have had mystical experiences often report that these events are so intense as to be transformative, e.g. “completely changed the direction of my life.”  A word of caution—there is an abundance of qualitative data reporting that these experiences can be emotionally agonizing. The terms “spiritual emergency” or “spiritual crisis” appear often enough to warrant caution.  

These are powerful substances. There is reason that they held a sacred place in religious practices.  So, it is extremely important that things like setting, medical supervision, and spiritual concerns are discussed prior to administration.  Ketamine finds itself in an interesting place. It appears to have some properties that treat depressive symptoms, while being less potent than the classical psychedelics.  Recent research suggest that we may come to recognize that the alleviation of depressive symptoms is just a byproduct of the actual psychedelic experience (Dore et al., 2019).


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