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.

Ketamine Unleashed

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 conditions (3).

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 anxiety disorders.

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-dependent phenomenon.

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 benefits from this innovative treatment approach.

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 emphasized 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 needs throughout ketamine-assisted journeying.

We were acutely aware of the importance 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 surrounded me.

Upon returning to a more grounded state, I felt the need to reestablish my connection with the tangible reality. 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 the importance 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 a major 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 a favorable atmosphere for therapeutic benefits.

Having Tina by my side as she underwent her own breakthrough experience with ketamine added an additional layer of relevance 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 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 mutual support.

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, 2019.