Dr. Zelko Leon
In his words...
FROM ANESTHETIC TO ANTIDEPRESSANT, AND MORE: THE FASCINATING STORY OF KETAMINE
Reshaping of the Ketamine
In the area of pharmaceutical breakthroughs, few substances have made a
transition as remarkable as ketamine. Originating from the mind of Dr. Calvin
Stevens, who worked for the pharmaceutical company Parke-Davis (now a part of
Pfizer), ketamine was conceived in 1962. Dr. Stevens wanted to replace the
problematic drug phencyclidine (PCP), due to its adverse side effects, with the
new, safer anesthetic (1).
During the 1970s and 1980s, ketamine rose to prominence, capturing the attention
of medical professionals. What set it apart from other anesthetics was its ability to
induce a sense of detachment from the surroundings, coupled with altered senses in
patients. The unique experience it offered, combined with its rapid onset and short-
lasting effects, proved invaluable in emergency situations and surgical procedures.
Yet, the story of ketamine did not end with its success as an anesthetic. In the late
1980s, scientists ventured beyond its traditional application exploring its
therapeutic benefits for treating depression. The idea that an anesthetic could be
used as an antidepressant was novel and exciting.
The paradigm shift occurred in the year 2000 when Dr. John Krystal and his team
at Yale University unveiled the extraordinary antidepressant effects of ketamine
(2). This publication catapulted ketamine into the limelight, keeping the attention
of researchers, doctors, and patients alike. Suddenly, hope emerged for the clearing
of the dark clouds of depression. The mere possibility of rapid and effective
treatment for this debilitating condition was nothing short of a revolution.
A flurry of clinical trials and research studies ensued not only for depression but
also for a myriad of other mental health conditions; the dawn of a new era in the
mental health field, a paradigm shift that would alter the way we treat these
Here's a very brief summary of ketamine's use in mental health:
Treatment-Resistant Depression (TRD): Ketamine has shown promise in treating
TRD, the type of depression that doesn't respond to regular antidepressant
treatments. It's given in small amounts through an IV drip, injection, or lozenge
under the tongue. Studies have found that many patients experience quick and
significant improvements in their depressive symptoms, often within a few hours
or days after treatment. The effects can last for days to weeks, but repeated
treatments may be necessary to maintain the benefits.
How it Works: We're not entirely sure how ketamine exactly works to alleviate
depression. In the past, it was believed to primarily block certain receptors in the
brain called N-methyl-D-aspartate (NMDA) receptors. However, recent research
suggests that another substance produced when ketamine breaks down, called
hydroxynorketamine, may also contribute to its antidepressant effects by
interacting with different receptors and pathways in the brain.
Other Mental Health Conditions: Aside from depression, ketamine has shown
potential in treating other mental health conditions like bipolar depression, post-
traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), and some
Safety and Side Effects: Ketamine is generally considered safe when used as a
short-term anesthetic. However, its long-term and repeated use for mental health
conditions is still being studied. Some common side effects of using ketamine
include feeling disconnected from your body, lightheadedness, an increase in blood
pressure, feeling nauseous, and experiencing temporary changes in heart rate.
Sometimes, people may also have disturbances in their perception, which is a dose-
Administration and Monitoring: When ketamine is used for mental health
treatment, it's usually given in controlled medical settings like clinics or hospitals,
with healthcare professionals supervising the process.
Exploring the Ketamine-Assisted Psychotherapy Model
The ketamine-assisted psychotherapy (KAP) model proposes distinct applications
of ketamine according to dose and mode, with lower-dose sublingual
administration recommended for sessions that involve more active therapist-patient
communication, and higher-dose intramuscular or intravenous administrations
recommended for sessions that adhere more closely to current models of
psychedelic psychotherapy with an inward focus, eye coverings and music (4). The
therapy is conducted by trained mental health professionals who have expertise in
both ketamine and psychotherapy. The effects of ketamine can induce an altered
state of consciousness, including dissociation, relaxation, and heightened
introspection. It is believed that these effects can potentially facilitate therapeutic
breakthroughs and provide unique insights during the psychotherapeutic process.
At the clinic where my wife, Tina, and I work, we have witnessed an emerging
trend in the use of ketamine as a viable treatment option for patients who have
previously shown little to no improvement with conventional therapies, especially
in cases of depression. The dedicated staff members at our clinic have undergone
extensive training to ensure the safe and appropriate administration of this
powerful medicine. In fact, both Tina and I have personally referred several
patients who have experienced significant benefits from this innovative treatment
During our regular staff meetings, we have actively engaged in discussions
surrounding the remarkable breakthroughs observed in patients undergoing
ketamine therapy. These discussions have not only served as a platform for sharing
success stories but have also highlighted the importance of empathy and
understanding in our role as healthcare providers. We recognized the need to gain
insight into the experiences our patients undergo during this therapeutic process
enabling us to offer more effective guidance and support to patients while
navigating through ketamine treatment.
Exploring the Inner Cosmos
With this in mind, Tina and I decided to accept the invitation and personally
explore the effects of ketamine. Soon after we made up our minds, I had the
opportunity to experience ketamine administered sublingually alongside my wife,
aided by the presence of two highly skilled clinicians who were trained to support
and ensure our safety throughout the entire course of the session which lasted
around two hours. Their presence was invaluable, as they took care of our physical
and mental safety throughout ketamine-assisted journeying.
We were acutely aware of the significance of being in the right frame of mind and
creating a secure and nurturing environment. We understood that these factors
would profoundly influence the nature of the experience that lay before us. Given
my recent focus on the theme of death in my writing, my intention was to
transcend the limitations of the physical world with the assistance of ketamine.
However, as is often the case with such deeply personal experiences, the outcome
did not unfold precisely as I had envisioned. Yet, this divergence from my original
expectations was not unexpected, as I acknowledged that I did not possess control
over the trajectory of my inner states.
Nonetheless, I had a mind-altering experience that went beyond normal perception.
I found myself absorbed in a fascinating world, filled with unfamiliar and
constantly changing shapes and colors, affected by the synesthetic connection to
the music playing in the background. Throughout the entire “trip,” I maintained
closed eyes, allowing myself to exist in two different realities at the same time. In
this strange state, I was fully aware of my physical surroundings, feeling the touch
of everything around me and the pulsations of my own body. But I also traveled
through a separate realm, a world full of mysterious and diverse visual patterns that
seemed to come from the very fabric of existence itself.
At one point, I briefly saw an eye or a face, but it quickly disappeared. Overall, this
journey allowed me to understand the fundamental nature of reality itself, which is
energy in its purest form. I couldn't be completely sure if I had control over what
was happening or if things were happening on their own, but I consciously chose
not to interfere and let the experience unfold naturally. Surprisingly, I managed to
let go and enjoy the process, feeling both intrigued and detached.
Throughout this vibrant expedition, I felt no fear or negative sensations. Instead, I
witnessed a variety of shapes and forms moving together in perfect harmony,
freeing me from the constraints of time. I lost track of how long I spent in this
realm because I was completely absorbed in the ever-changing abstract visuals that
Upon returning to a more grounded state, I felt the need to reestablish my
connection with the tangible reality surrounding me. To initiate this reconnection, I
started by intentionally flexing my toes and fingers and engaging my physical
senses. With each deliberate movement, I gradually transitioned from a reclined
position to being seated, and finally summoned the strength to stand up, even
though with a slight unsteadiness in my steps. The remnants of the ketamine
experience were still apparent, as I was aware of a lingering sense of disinhibition
and euphoria that underscored my inner mental state. Fortunately, we have
considerate neighbors who kindly drove us back home, facilitating a safe and
seamless transition to our familiar environment.
Reflections on Ketamine's Contact with the Human Mind
My experience with ketamine served as a testament to the enormous potential of
the human mind to open up the unexplored realms of consciousness. While my
objective may not have been fully realized, it is a reminder of the unpredictable
nature of such ventures that are unique for each individual. I was also reminded of
the importance of surrendering control and embracing the unknown, as it is within
these moments of vulnerability that the most profound discoveries can emerge.
Ultimately, the exploration of ketamine's effects not only enriched and deepened
my understanding of the complexities of human existence but also highlighted the
significance of supportive companionship and a conducive environment. These
insights will undoubtedly inform and enhance my work with patients who are
undergoing this remarkable treatment.
Creating a space that is tranquil, comfortable, and aesthetically pleasing has an
important impact on the overall experience. Attention to detail, such as soothing
lighting, calming music, and comfortable furnishings, contribute to a sense of
relaxation and facilitate a deeper connection with oneself. These environmental
elements, when thoughtfully curated, complement the therapeutic benefits of
ketamine and create an atmosphere conducive to profound therapeutic benefits.
Having Tina by my side as she underwent her own breakthrough experience with
ketamine added an additional layer of significance for me. The presence of a like-
minded companion enhanced the value of our individual experiences, allowing us
to share and explore the effects of ketamine together. I am looking forward to
continuing our conversations about this unique and transformative encounter with
ketamine. The bond we formed through this shared experience deepens our
connection and provides us with a platform for ongoing reflection, growth, and
1. Pharmacologic Effects of Ci-581, a New Dissociative Anesthetic, in Man, by Domino EF,
Chodoff P, Corssen G., Clinical Pharmacology & Therapeutics; 6(3):279-291, 1965
2. Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans:
Psychotomimetic, Perceptual, Cognitive, and Neuroendocrine Responses, by Dennis S. Charney,
John H. Krystal et al., Archives of General Psychiatry; 57: 270-276, 2000
3. Ketamine for the treatment of mental health and substance use disorders: a comprehensive
systematic review, by Zach Walsh et al., Br J Psychiatry Open, 8: 1-12, 2022
4. Ketamine-assisted psychotherapy (KAP), by J. Dore et al., J Psychoactive Drugs; 51: 189–98,