Ketamine: Menace or Miracle?

Doc G on Special K

By Michael Jorrin, "Doc Gumshoe", January 21, 2019

I’ll grant that my headline is meant to be catchy and induce you to read this epistle.   Some of you will ask what is ketamine anyway, and most of you will know from the get-go that ketamine, whatever the heck it is, will turn out to be neither a menace nor a miracle, but something in between.   I make that prediction because, before I started the digging process, that’s exactly where I was.

I had heard of ketamine as one of those “party drugs” that came along after LSD and its shady relatives, and I knew vaguely that some people – including some supposedly well-credentialed health-care professionals – were touting the usefulness of ketamine in certain situations.   But then, thought I, no matter what the substance is, there will be some people who authoritatively claim that the particular substance in question will cure one or more serious health conditions, e.g., tiny doses of cyanide as a cure for cancer (remember laetrile and apricot pits?)

What prompted me to look at ketamine a bit more closely was a densely-written paper in The American Journal of Medicine entitled “Nonanaesthetic Effects of Ketamine: A Review Article,” by a group of physicians at the University of Montreal (Eldufani J. Am J Med 2018;131:1418-1424).   What first caught my attention was a box listing the highlights of the paper, which I reproduce here:

CLINICAL SIGNIFICANCE

  • Ketamine has a variety of pharmacologic effects including sedation, analgesia, bronchodilation, and nervous system stimulation.
  • It is used as an active adjutant that prolongs the duration of analgesic effects of painkillers in pain management.
  • Ketamine is used in clinical practice to manage major resistant depression, enhance memory function in Alzheimer’s patients, and reduce brain damage after stroke.
  • Ketamine is clinically used for managing cognitive dysfunction and immune system disorders.

As I looked through the review article, I was especially struck by the characteristics of this drug when used as an anaesthetic.   What most anaesthetics do along with suppressing pain responses and inducing loss of consciousness is to slow respiratory function and heartbeat.   This is true of opiates, whether taken purely for pain management or for other purposes. What kills people who overdose on opiates is, pure and simple, that they quit breathing.   And anaesthesiologists are extremely scrupulous about monitoring their patients’ breathing and heart rate. They want to make absolutely sure that their patients don’t quietly drift off into permanent oblivion.   But when ketamine is used as an anaesthetic, depressed respiratory function simply is not a problem. And, as the title of that review article implies, anaesthesia was the initial medical use of ketamine. Because it preserved respiratory function, it was used as a battle-field anaesthetic during the Vietnam War, and medics in the US military always have it at the ready.   

But before we get too far ahead of ourselves, let’s do some groundwork.

So, what is ketamine?

Ketamine is a small molecule related to phencyclidine, which was discovered in the 1950s and originally used as an anaesthetic.   However, the use of phencyclidine as an anaesthetic was discontinued fairly soon when a number of significant neurotoxic side effects emerged.   Phencyclidine was taken up as a recreational drug in part because of some of those neurotoxic side effects such as delusions and hallucinations.  It is sometimes called “angel dust” by its recreational drug fans.

Ketamine was discovered in 1962, tested in humans in 1964, and approved by the FDA in 1970, shortly after which it was widely used in the Vietnam War.   It is on the World Health Organization’s List of Essential Medicines, and is widely available in the generic form.

Ketamine rapidly passes the blood-brain barrier to produce an analgesic effect.   The principal mechanism of action of ketamine is that it is an antagonist of the N-methyl-D-aspartate (NMDA) re