Ketamine: How We Got Here

Ketamine is a man-made pharmaceutical synthesized in the 1960s. Scientists had actually created phencyclidine (PCP – yes, that drug) in the 1920s and used it as an anesthetic for several decades. Due to the extreme of its psychological effects, it fell out of favor and companies set out to create a similar compound without this effect, and that was ketamine. Ketamine is similar in structure to PCP but at nearly 1/10th the potency is able to induce the desired anesthesia results with much less psychoactive impact. In 1970, Ketalar was FDA approved as a new human anesthetic and a very safe one at that – without cardiac or respiratory effects like many other anesthetics, it has been the anesthetic of choice for short procedures on children and pregnant women, and continues to have a stellar safety profile in the way of few adverse events.

While the psychoactivity of ketamine was still viewed as an unwanted side effect, a few psychedelic pioneers explored the use of it in the context of psychotherapy.  The Maryland Psychiatric Institute, already doing research on LSD, invited one of these pioneers, Salvador Roquet, to help research ketamine in this space. However, in the 1970s with the growth of overall recreational drug use, Nixon created the DEA and declared a “war on drugs” classifying many psychedelic substances in the Schedule I category, rendering them illegal. This effectively shut down the Psychiatric Institute – and any research in psychedelics in the U.S. – as the negativity and stigma toward these substances grew. Outside of the U.S., however, research continued. As reports grew on the potential of ketamine for clinical applications apart from anesthesiology so did research in the States, starting in the early 2000s. A handful of clinical trials since then has shown much promise for ketamine, mostly focused on treatment resistant depression and suicidality. Unfortunately, the toxicity of Nixon’s “war on drugs” has kept a shadow over ketamine, slowing its adaptation for use in this space. Compounding this, pharmaceutical companies are not financially motivated to spend the multi-millions of dollars needed to run the robust clinical trials for FDA approval as this old drug is not going to make them money. This poses a bit of a battle for ketamine to become standard of care. 

How It works

As with nearly every pharmaceutical, we don’t fully understand all targets of ketamine within the body but we do know it primarily involves NMDA receptors and glutamate – a different mechanism than what medications currently available for mood disorders offer. For simplicity’s sake, ketamine’s main action is in blocking neuronal mechanisms in the brain designed to put the breaks on other neurons. This increases glutamate activity that has downstream biochemical effects we are still investigating. Among them are positive influences on neurotrophic factors that can increase neuron growth and communication. It is this aspect of ketamine that is hypothesized to be behind its anti-depressant effects. Mechanism of action aside, however, my firm belief is that it is not just the biochemical activity that is helpful, but the psychotropic/psychedelic experience itself. From a spiritual aspect, I have a personal understanding of what the psychedelic experience is but, even without this understanding, anyone can benefit from the perplexing and often awe-inspiring journey the psychedelic experience can be. Because it is such an abrupt departure from how the brain is used to behaving and thinking, it allows for a shift in our perception that can beget lasting changes in thought behavior, even after the experience has ended. It is this shift that becomes such a profound healing tool for many. 


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