History of Ketamine in Psychiatric Medicine

History of Ketamine

“Ketamine’s history begins with Phencyclidine, which was first synthesized in 1956 by chemists at Parke Davis Company who discovered Ketamine’s unique and fascinating pharmacology”(Maddox et al., 1965, as cited in Li and Vlisides, 2016). Ten years later, it was approved as a human anesthetic (Li and Vlisides, 2016) and is currently administered via the intravenous, intraosseous, intramuscular, oral, nasal, and rectal routes (Marland et al., 2013). The need for Ketamine first came about after the use of PCP in the ’40s when it was discovered that PCP left people in a psychotic state (Kelly, 2020). Ketamine was found to have no psychotic after-effects and lasted for a shorter period of time. This was great timing as the Vietnam War was raging, and medication was needed to put patients under without an operating room. The drug was soon patented in 1963 by Belgium and soon after by The United States (Britannica, n.d.). Eventually, in 1970 Ketamine was approved as an anesthetic by the Food and Drug Administration (FDA) (Wei et al., 2020).

During the late 60s and early 1970s, the abuse of Ketamine was becoming more apparent and available on the streets. Ketamine was first marketed in the 1970s and first appeared in the U.S. on the West Coast in 1971 (WHO, n.d.). The time period quickly became famous for exploring one’s mind and escaping the trauma associated with war. A German writer, Ernst Jünger, coined the term “Psychonaut,” which means “Sailors of the soul,” in 1970. Psychonauts were known to “Seek altered states of consciousness to search for truth in the unconscious mind” (Grinnell College, n.d.). This search for truth was often accomplished through psychedelic drugs like Ketamine. The word spread about the recreational uses of Ketamine in the 60s and ’70s as more people began to document their experiences.

“Psychiatric and academic researchers published other literature regarding Ketamine usage and the effects of Ketamine intoxication to explore the inner psyche and other altered states of consciousness. The popularity of recreational Ketamine usage rose with the publication of two books in the late 1970s, describing personal accounts of its use: ‘Journeys into the Bright World’ by Marcia Moore and Howard Alltounian and ‘The Scientist’ by John Lilly” (“Ketamine,” n.d.).

Marcia Moore’s book “Journeys into the Bright World” questioned the future of ketamine for therapeutic and medicinal benefits. An excerpt from the introduction noted, “Why are the ‘mind-manifesting’ drugs still regarded with so much fear? Can it be because modern science still lingers on the threshold of the unconscious, hesitating to knock too loudly for fear of what might be revealed if the door should open?” (Moore, 1978, p. 4). It seems that she was quite prescient about what the future had in store regarding scientific and medicinal discoveries with psychedelics and dissociatives like Ketamine.

In the 1980s, John Lilly, who wrote “The Scientist,” was one of Ketamine’s most prominent advocates. He was both a doctor and psychoanalyst but was best known for “Using sensory deprivation tanks and dabbling in human-dolphin communication” (Witt, 2021). He was an avid user of Ketamine via injection. Although he supposedly stopped using the drug recreationally in his 60s, it is said that he resumed later on in life.

After its time as a party drug in the 1990s, under various names including K-Hole, Special K, and Kit-Kat, Ketamine took a more serious tone. The rampant abuse of Ketamine led to its drug classification as a Schedule III drug after the US Controlled Substances Act went into effect. The DEA defines a schedule III drug as “Drugs, substances, or chemicals, with a low physical and psychological dependence potential. Schedule III drugs abuse potential is less than Schedule I and Schedule II drugs but more than Schedule IV” (Drugs Enforcement Administration [DEA], n.d.).

During the 1990s, studies were conducted reviewing the effects of Ketamine on humans to determine how it could be utilized in the mental health industry. “Krystal et al., in 1994 assessed both four key positive and three negative symptoms of schizophrenia in healthy subjects after administration of 0.1 or 0.5 mg/kg of Ketamine.” Similarly, Adler et al. conducted a study on Ketamine and the effects of thought disorder compared with thought disorder patients with schizophrenia.

Researchers at Yale in the 1990s wanted to understand if Ketamine could be used as an antidepressant. The studies revealed that “Ketamine triggers Glutamate production, which, in a complex, cascading series of events, prompts the brain to form neural connections. This makes the brain more adaptable and able to form new pathways and allows patients to develop more positive thoughts and behaviors. This effect had not been seen before, even with traditional antidepressants” (Chen, 2022). However, other scientists were skeptical and did not think depression symptoms could quickly improve. Dennis Charney, a fellow researcher and Dean of the Icahn School of Medicine at Mount Sinai, tried to replicate the study with more patients. The results were published in 2006 and confirmed what was initially thought: Ketamine’s rapid antidepressant effect was highlighted to show that the drug was able to treat other psychiatric conditions as well. (Torrice, 2020).   

The Ketamine industry has been rapidly expanding into the mental health industry, especially throughout the past few years; “on March 5, 2019, the Food and Drug Administration [FDA] approved the first new medication for major depression in decades. The drug is a nasal spray called esketamine (Spravato®), derived from Ketamine which has been touted for its antidepressant effect”(Chen, 2022). John Krystal, the chief psychiatrist at Yale Medicine, and Carolyn Rodriguez, a Stanford psychiatrist, have called Esketamine (Spravato®) a “game-changer”(Chen, 2022). However, the drug is being met with skepticism as more research still needs to be done. Questions awaiting answers include, “For how long should the patient receive the drug? The clinical trial for esketamine (Spravato®) treated patients for over a year, but is it safe on a long-term basis? And what happens if a patient stops taking the drug?”

While it takes time for new medications to be approved for trials and then by the FDA, time is of the essence. The global pandemic has exacerbated the mental health crisis and put many in jeopardy:

“We entered the pandemic with rising rates of suicide across all child and adolescent populations, and the rates continue to rise. Our mental health resources were limited before COVID-19 but became even more limited when out of caution, intensive and acute care services restricted access further. While we must think broadly about improving access to mental health care for youths across the continuum of care, prioritizing innovative treatments like rapid-onset antidepressant medications to reduce acute suicide risk should be at the top of the national mental health agenda” (Parikh et al., 2021).

Avesta Ketamine & Wellness forges ahead, offering this revolutionary medicine in a professional and clinical setting. With our ketamine infusion treatment options and Spravato ® treatments, you can treat various ailments that may hold you back in your daily life: chronic pain, depression, addiction, treatment-resistant depression, PTSD, and so much more. Don’t hesitate to start living your life - contact us today for your free consultation!



Li, L. & Vlisides, P. (2016). Ketamine: 50 Years of Modulating the Mind. National Center for Biotechnology Information. 10(612), 10.3389/fnhum.2016.00612.

Marland, S. et al., (2013). Ketamine: Use in Anesthesia. National Center for Biotechnology Information, 19(6), 381-389, 10.1111/cns.12072

Domino, E MD. and Warner, D MD. (2010). Taming the Ketamine Tiger. American Society for Anaesthesiologists, 113, 678-684, https://doi.org/10.1097/ALN.0b013e3181ed09a2

Kelly, S. The Many Lives of Ketamine. The MIT Press Reader. (October 20, 2020). Retrieved March 15, 2022, from https://thereader.mitpress.mit.edu/the-many-lives-of-ketamine/

Rogers, K. Ketamine. Britannica. (February 9, 2022). Retrieved March 18, 2022, from  https://www.britannica.com/science/ketamine

How Psychedelic Medicine Works in the Brain. Save Minds. (March 17, 2021). Retrieved March 15, 2022, from https://saveminds.co.uk/how-ketamine-works-in-the-brain/

Psychonauts. Grinnell College Subcultures and Sociology. (n.d.). Retrieved March 15, 2022, from https://haenfler.sites.grinnell.edu/subcultures-and-scenes/psychonauts/

Drug Scheduling. Drug Enforcement Administration (DEA). (n.d.). Retrieved March 15, 2022, from https://www.dea.gov/drug-information/drug-scheduling

Moore, M. and Alltounian, H. (1978). Journeys into the Bright World. Para Research Inc. http://pdf.textfiles.com/books/journeysbrightworld.pdf

History of Ketamine. Ketamine. (n.d.). Retrieved March 15, 2022, from https://ketamine.com/history-of-ketamine/

Ketamine. Drug Enforcement Administration (DEA). (n.d.). Retrieved March 15, 2022, from https://www.deadiversion.usdoj.gov/drug_chem_info/ketamine.pdf

Parikh, T. and Walkup, T. The Future of Ketamine in the Treatment of Teen Depression. (2021). American Journal of Psychiatry, https://doi.org/10.1176/appi.ajp.2020.21020172https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2020.21020172.

How Did Ketamine Go From Party Drug to Treatment Method? Albany Ketamine Infusions. (June 10, 2019). Retrieved March 15, 2022, from https://albanyketamine.com/how-did-ketamine-go-from-party-drug-to-treatment-method/

Georges, M. History of Anaesthesia. (2017). European Journal of Anaesthesia, 34(9), 571-575, 10.1097/EJA.0000000000000638.

Critical Review of Ketamine. WHO. (n.d.). Retrieved March 15, 2022, from https://www.who.int/medicines/areas/quality_safety/4.3KetamineCritReview.pdf

Chen, J. How Ketamine Drug Helps With Depression. Yale Medicine. (March 9, 2022).  Retrieved March 15, 2022, from https://www.yalemedicine.org/news/ketamine-depression

Torrice, M. Ketamine is Revolutionizing Antidepressant Research, But We Still Don’t Know How It Works. Chemical and Engineering News. (January 15, 2020). Retrieved March 15, 2022, from https://cen.acs.org/biological-chemistry/neuroscience/Ketamine-revolutionizing-antidepressant-research-still/98/i3

Dr. Ladan Eshkevari, PhD, CRNA, FAAN Dr. Eshkevari is the lead clinician at Avesta, and is a long time researcher and educator in physiology, biophysics, and anesthesiology. She is passionate about assisting patients with retractable, difficult to treat mood disorders, and relies on the latest research to bring evidence to Avesta's practice to better understand and serve patients.

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