News & Publications

KRF Publications

The History of Ketamine in Medicine: From Anesthesia to Depression Treatment


Ketamine, a powerful dissociative anesthetic, has a long and fascinating history in the field of medicine. Originally developed in the early 1960s as a safer alternative to phencyclidine (PCP), ketamine quickly gained popularity for its unique properties and wide range of applications. In this article, we will explore the journey of ketamine from its discovery as an anesthetic to its groundbreaking use in treating depression.

The Discovery and Early Uses

Ketamine was first synthesized by Dr. Calvin Stevens in 1962 while working at Parke-Davis Laboratories. Initially known as CI-581, it was intended to be a safer alternative to PCP, which had significant side effects. However, ketamine’s anesthetic properties were soon discovered during animal testing, leading to its introduction as a medical anesthetic in the late 1960s.

Anesthesia and Surgical Applications

Ketamine quickly became a popular anesthetic due to its unique properties. Unlike traditional anesthetics, ketamine provides both sedation and analgesia while maintaining respiratory function and cardiovascular stability. This made it particularly useful for surgical procedures, especially in resource-limited settings where access to specialized equipment and monitoring capabilities is limited.

Ketamine’s ability to induce dissociation, a state of profound anesthesia, also made it valuable in situations where patients needed to be disconnected from their surroundings and experience minimal pain. Its use in pediatric anesthesia, in particular, gained traction due to its safety profile and effectiveness.

Ketamine in Emergency Medicine

In addition to its role as a surgical anesthetic, ketamine found a niche in emergency medicine. Its rapid onset of action and hemodynamic stability make it an ideal choice for procedures such as reducing fractures, resetting dislocations, and managing acute pain. Ketamine’s ability to maintain airway reflexes and spontaneous breathing also makes it valuable in emergency situations where intubation may not be immediately feasible.

Emergency departments have utilized ketamine for procedural sedation, especially in cases involving agitated or combative patients. Its dissociative properties provide a calm and controlled environment for healthcare providers to perform necessary interventions safely.

Beyond Anesthesia: Ketamine’s Rising Potential

While ketamine’s anesthetic properties have been widely recognized and utilized, its potential for treating mental health conditions, particularly depression, has recently garnered significant attention. In the early 2000s, researchers began exploring the effects of ketamine on individuals with treatment-resistant depression. The results were groundbreaking.

Ketamine as an Antidepressant

Studies have shown that ketamine, administered in subanesthetic doses, can rapidly alleviate symptoms of depression, even in patients who have not responded to traditional antidepressant medications. The exact mechanisms of ketamine’s antidepressant effects are still being studied, but it is believed to involve the modulation of glutamate, a neurotransmitter involved in mood regulation.

Ketamine’s ability to stimulate the regrowth of neural connections in the brain, particularly in the prefrontal cortex, may contribute to its antidepressant properties. It is thought to promote the release of brain-derived neurotrophic factor (BDNF), a protein that supports the growth and survival of neurons. The rapid onset of ketamine’s antidepressant effects, often experienced within hours, provides hope for individuals who have struggled with treatment-resistant depression.

The Rise of Ketamine Clinics

As the evidence supporting ketamine’s efficacy in treating depression grew, specialized ketamine clinics started to emerge. These clinics offer ketamine infusion therapy as a treatment option for individuals with treatment-resistant depression. Ketamine infusions, administered under medical supervision, have shown promising results in providing rapid relief from depressive symptoms.

Ketamine clinics typically follow a comprehensive approach, involving careful patient evaluation, personalized treatment plans, and close monitoring of treatment response. The administration of ketamine may involve intravenous infusions or intranasal formulations, depending on the clinic’s protocols and individual patient needs.

Future Directions and Challenges

While ketamine has shown remarkable potential in the treatment of depression, many questions and challenges remain. Long-term effects, optimal dosing protocols, and the sustainability of treatment effects are areas of ongoing research. Additionally, the high cost of ketamine therapy and access barriers pose challenges for widespread implementation.

Researchers are actively exploring ways to improve the long-term outcomes of ketamine treatment, including optimizing maintenance strategies and identifying predictors of treatment response. Efforts are also underway to develop alternative formulations and delivery methods that can enhance the convenience and accessibility of ketamine therapy.


Ketamine has come a long way since its discovery as a safer alternative to PCP. From its humble beginnings as an anesthetic, it has evolved into a promising treatment for depression. As ongoing research continues to unravel the mechanisms behind ketamine’s effects, it is hoped that this remarkable substance will continue to pave the way for new frontiers in mental health treatment.


  1. Domino EF, Chodoff P, Corssen G. Pharmacologic effects of CI-581, a new dissociative anesthetic, in man. Clin Pharmacol Ther. 1965;6(3):279-291.
  2. Newport DJ, Carpenter LL, McDonald WM, et al. Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression. Am J Psychiatry. 2015;172(10):950-966.
  3. Sanacora G, Frye MA, McDonald W, et al. A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. JAMA Psychiatry. 2017;74(4):399-405.
The History of Ketamine in Medicine: From Anesthesia to Depression Treatment



More News & Publications