This piece was published in collaboration with our wonderful partners at Ketamine Media. Find more great content by Ketamine Media on the Microdose blog here!

 

Since making its clinical debut in the 1960s, the dissociative anesthetic drug ketamine continues to marvel scientists and clinicians with its unique ability to modulate the mind. What began as a novel anesthetic graduated to become a staple in critical care and anesthesiology, and is more recently being repurposed as a radically effective treatment for difficult to manage pain and neuropsychiatric conditions. Outside the clinical and research setting, ketamine has played a notably contrasting role as a hallucinogenic compound commonly sought after for its psychedelic and dissociative properties. The compound’s curious journey from age-old anesthetic to novel antidepressant (and beyond) offers significant promise in the treatment of mental health issues for the world at large, and is bolstered by decades of sound clinical trials establishing its safety. For this reason, new ketamine-based therapeutics have a unique advantage over new, untested compounds, given its position to effectively maneuver regulatory hurdles and clear FDA guidelines. This guide will explore the evolution of ketamine therapeutics, including its introduction to medical practice as an anesthetic, its evolution into a powerful treatment for mental health and acute pain, as well as its future uses beyond clinical applications, such as to potentially enrich the human experience through a process dubbed “human optimization.”

 

A Look to The Past: The Beginnings of Ketamine in Clinical Practice

 

Ketamine began its journey in clinical practice when Corssen and Domino published the first clinical study of ketamine as a human anesthetic in a 1966 report.1 Developed as a weaker and more viable analogue to phencyclidine (PCP), which caused intense and prolonged “emergence delirium” in humans, ketamine quickly became a staple in the theory and practice of critical care and anesthesia.2 Synthesized by chemists at Parke Davis Company and formerly identified as CI-581, the structural PCP-analogue was one-tenth the strength of its parent compound and much shorter acting. Curiously enough, the name ketamine is derived from the fact it is a novel combination of a ketone and an amine.3 The first human anesthetic dose administered by Domino and Corssen on August 3rd, 1964, eventually led to their aforementioned clinical trials two years later, establishing the safety and efficacy of ketamine for clinical anesthetic use.2 They demonstrated that ketamine could indeed produce rapid and profound pain killing effects, as well as uniquely alter consciousness for only a short time, which could easily be extended with repeated administration.2 In 1970, the first pharmaceutical preparation of ketamine, called Ketalar, was approved by the Food and Drug Administration for human use.4 Ultimately, ketamine’s unique ability to “maintain cardiorespiratory stability while providing effective sedation and analgesia,” established the drug as an invaluable tool in emergency medicine and anesthesiology.2 From here, its role in medicine, particularly in anesthesia, quickly became that of a “gold standard” with widespread use worldwide. While these historic strides in anesthesia and drug development surely went on to reshape the entire medical practice of surgery and our understanding of the anesthetized state in humans, the extraordinary and versatile role of ketamine in medicine was only just emerging.

 

A Look to The Present: Neuropsychiatric Applications of Ketamine Today

 

Ketamine may have started as an incredibly safe and effective anesthetic agent, but its bold journey doesn’t stop there. Today, sub-anesthetic doses are being administered in boutique clinics across the country to radically treat difficult mental health conditions, like treatment-resistant depression,5 acute suicidality,6 PTSD,7 and anxiety.8 Even a cursory investigation of the promising clinical data surrounding the neuropsychiatric applications of this novel medicine reveals that it may indeed be the revolutionary breakthrough in mental health treatment we have been waiting for. Psychiatrist Dr. Abid Nazeer, an expert in the field, has successfully treated many patients with Ketamine infusion therapy in his Oakbrook clinic, APS Ketamine. “It’s much better than anything we’ve had before,” states Dr. Nazeer in a Chicago Tribune article. “I’ve seen it work so quickly that one infusion gets rid of suicidal thoughts that had been there for 20 years.” While the exact neuropharmacological mechanisms by which ketamine can profoundly and rapidly induce a clinically significant and lasting anti-depressant effect are unknown, it is thought to induce the formation of new neural connections via a neurotransmitter called BDNF that essentially aids in remodeling the human brain.9 As the exciting and innovative research into ketamine’s incredible potential as a mental health medicine evolves, ketamine’s analgesic potential is also garnering much attention in the modern day.

  

How Ketamine Is Addressing the Dire Need for Effective New Pain Management Strategies

 

Since it can provide incredible pain relief without compromising cardiorespiratory stability, ketamine is becoming an increasingly popular option in managing pain during surgery, and more importantly, immediately after surgery, due to its “impressive safety profile” and ability to provide “excellent analgesia.”2 Eventually, ketamine would end up finding its way into the post-operative care setting where opioid drugs play a fundamental role, but are accompanied with various risks and adverse effects. A brief glance at the current opioid epidemic gripping America speaks volumes of this grim reality. Even in battlefield combat, morphine (the quintessential opioid painkiller) is “slipping” as the gold standard. “The United States Defense Health Board notes that morphine is the slipping gold standard in Tactical Combat Casualty Care pain management and recommends ketamine as a new alternative to battlefield analgesia.”10 Indeed, bold companies, like Bexson Biomedical, are pioneering ketamine-based therapeutics for not only managing acute, postoperative pain, but potentially preventing the graduation of acute pain into chronic pain, another significant global affliction and socioeconomic burden.

 

Learn more about Bexson Biomedical’s ambitious plan to develop novel ketamine therapy for-home use for post-operative pain, a $12 billion dollar market, in this evidence-based blog and at our upcoming Ketamine Molecular Masterclass

 

A Look to The Future: Ketamine Sets A Bold Precedent for The Future of Psychedelic Therapy

 

As ketamine therapy gains momentum in treating mental health and pain in the modern day, many are looking ahead to an even brighter future. Since ketamine has been extensively studied and has an established, favorable safety profile, it has unique advantages in terms of regulatory hurdles compared to new chemical compounds. For this reason, this clinically familiar hallucinogen may be the bridge between traditional medicine and the rapidly emerging, next generation of psychedelic medicine and therapy. With the increasing prevalence of anxiety and depression among Millennials and Gen Z’ers, ketamine is poised to possibly offer a safer, more effective solution for youth mental health treatment. Anthony El Chibani, managing partner of Ketamine Media says, With suicide being the 2nd leading cause of death for 15 to 24-year-old Americans according to the CDC, it is imperative that we focus on the youth. There is a cultural shift happening right before our eyes and over the next decade, Millennials and Gen Z’ers will be the primary generations using psychedelics in the clinical setting. We must bridge the gap between medicine and culture to eliminate the stigma surrounding psychedelic therapy.” Combined with generational trends placing more focus on holistic health and sustainable wellness, experts predict that the future of ketamine therapy is expected to be bright across the spectrum, from healthcare to finance.

 

Going Beyond Disease: Profoundly Enriching Our Paradigm of Health & Wellness

 

Going beyond the scope of serious pain and mental illness, the real potential of psychedelic-assisted therapy lies in its ability to enrich the human experience and offer a profound paradigm shift in the way we approach health, wellness, and our understanding of ourselves. Groundbreaking new research suggests psychedelic therapy can radically promote “lasting change from experiential avoidance to acceptance” that shows “substantial parallels” to cognitive behavioral therapy (CBT).11 Indeed, the aphorism that psychedelics can facilitate many years of psychotherapy in just a few sessions (possibly even faster, considering the rapidity of onset of ketamine’s beneficial effects) is one of the great promises of the future. The type of anti-depressive and anxiolytic effects exerted by ketamine are reminiscent of the “quiet mind” sought after by meditation and mindfulness practitioners. Indeed, the movement to expand consciousness and further explore “the cartography of inner space” is certainly not separate from the psychedelic revolution, but powerfully intertwined with it.11 The unique ability of compounds like ketamine and more traditional psychedelics to create similar brain states as those achieved in transcendental meditation, highlight the incredibly powerful future implications that psychedelic therapy stands to offer the world at large. As this exciting movement gains speed, ketamine therapy is in the unique and dynamic position to revolutionize much more than just medicine. Rather, it has the potential to pioneer the path forward to a richer, fuller, and more prosperous human experience.

 

 

Works Cited

 

  1.     Corssen, G. & Domino, E. F. Dissociative Anesthesia: Further Pharmacologic Studies and First Clinical Experience with the Phencyclidine Derivative Cl-581. Anesth. Analg. 45, 29–40 (1966).
  2.     Li, L. & Vlisides, P. E. Ketamine: 50 Years of Modulating the Mind. Front. Hum. Neurosci. 10, (2016).
  3.     Mion, G. History of anaesthesia: The ketamine story – past, present and future. Eur. J. Anaesthesiol. EJA 34, 571–575 (2017).
  4.     Drugs@FDA: FDA-Approved Drugs. https://www.accessdata.fda.gov/scripts/cder/daf/#apphist.
  5.     Mandal, S., Sinha, V. K. & Goyal, N. Efficacy of ketamine therapy in the treatment of depression. Indian J. Psychiatry 61, 480–485 (2019).
  6.     The effects of ketamine on suicidality across various formulations and study settings. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322816/.
  7.     Liriano, F., Hatten, C. & Schwartz, T. L. Ketamine as treatment for post-traumatic stress disorder: a review. Drugs Context 8, (2019).
  8.     Taylor, J. H. et al. Ketamine for Social Anxiety Disorder: A Randomized, Placebo-Controlled Crossover Trial. Neuropsychopharmacology 43, 325–333 (2018).
  9.     Björkholm, C. & Monteggia, L. M. BDNF – a key transducer of antidepressant effects. Neuropharmacology 102, 72–79 (2016).
  10.   Wedmore, I. S. & Butler, F. K. Battlefield Analgesia in Tactical Combat Casualty Care. Wilderness Environ. Med. 28, S109–S116 (2017).
  11.   Richards, W. A. Psychedelic Psychotherapy: Insights From 25 Years of Research. J. Humanist. Psychol. 57, 323–337 (2017).