The History of Ketamine: From Anesthetic to Depression Breakthrough

Short answer: Ketamine was first synthesized in 1962 as a safer surgical anesthetic, approved by the FDA in 1970, and used for decades in operating rooms and on the battlefield. Only around the year 2000 did researchers discover its remarkable, rapid effect on depression, a finding that reshaped modern psychiatry and led to the FDA approval of its cousin esketamine in 2019. Here is the surprising story of how a medicine cabinet staple became one of the most talked-about advances in mental health.

1962: a search for something safer

Ketamine's story begins in a lab. In 1962, a team led by Calvin Stevens, a chemistry professor working with the pharmaceutical company Parke-Davis, synthesized a new molecule then known as CI-581. The goal was practical: to find a safer anesthetic than the drugs available at the time, which could cause dangerous agitation and hallucinations. The new compound looked promising.

1964: the first human trials

Two years later, in 1964, the first human trials began under researchers Edward Domino and Guenter Corssen. Volunteers described feeling disconnected from their bodies and surroundings, a strange, floating detachment. It was Domino's wife who reportedly suggested the term that stuck: a "dissociative" anesthetic. That word still describes the core of the ketamine experience today.

1970: approved, and sent to war

The FDA approved ketamine as an anesthetic in 1970, under the brand name Ketalar. It quickly earned a reputation as remarkably safe and reliable, because it provides pain relief and sedation without suppressing breathing and blood pressure the way many anesthetics do. That safety profile made it invaluable in field medicine, and it became a standard battlefield anesthetic for military medics. To this day, ketamine sits on the World Health Organization's list of essential medicines.

The turn of the century: an unexpected discovery

For its first few decades, ketamine was simply a trusted anesthetic. The plot twist came around the year 2000, when researchers ran a small, careful study and found something startling: a single low dose of ketamine could lift severe depression within hours, in people who had not responded to conventional antidepressants. Traditional medications can take weeks to work, if they work at all. This was a fundamentally different kind of effect, and it opened an entirely new direction in the treatment of depression.

The 2000s and 2010s: from finding to treatment

Over the following years, more studies confirmed the rapid antidepressant effect, and researchers began mapping how ketamine works on the brain's glutamate system to help rebuild connections. Clinics began offering low-dose IV ketamine off-label for treatment-resistant depression, and it gained particular attention for its speed in people at acute risk. What had started as a surgical anesthetic was becoming a lifeline for people out of options.

2019: FDA approval for depression

The milestone came in 2019, when the FDA approved esketamine, a nasal-spray form derived from part of the ketamine molecule, under the brand name Spravato, specifically for treatment-resistant depression. It was the first genuinely new mechanism approved for depression in decades, and it brought ketamine's promise into a standardized, regulated framework. IV ketamine, meanwhile, continues to be used off-label, valued for its flexibility and rapid effect.

Where things stand today

Today, ketamine occupies a unique place in medicine: a decades-old anesthetic with an established safety record that has become one of the most significant developments in depression care in a generation. It is not a cure, and the science is still evolving, but for many people who had run out of options, it has been a turning point. You can read more about how ketamine works in the brain and how we approach ketamine therapy for depression.

This article is for educational purposes only and is not medical advice. Ketamine is a controlled medication that should be given under medical supervision.

The bottom line

Ketamine began as a 1960s anesthetic, proved itself in operating rooms and on the battlefield, and then, around 2000, revealed a rapid and unexpected power to ease depression, leading to the 2019 approval of esketamine. It is a rare case of an old, trusted medicine opening a new door for people who needed one. If you are curious whether it might help you, call us at (310) 280-4440.

Frequently asked questions

When was ketamine invented? Ketamine was first synthesized in 1962 by a team led by chemist Calvin Stevens at Parke-Davis, as part of a search for a safer anesthetic. It was FDA-approved as an anesthetic in 1970.

What was ketamine originally used for? As a surgical and emergency anesthetic. It was prized for being safe and reliable, and became a standard battlefield anesthetic. It remains on the World Health Organization's list of essential medicines.

When was ketamine first used for depression? The rapid antidepressant effect was identified in a landmark study around the year 2000, and further research over the following years established it as a promising option for treatment-resistant depression.

When was Spravato approved? Esketamine, sold as Spravato, was approved by the FDA in 2019 for treatment-resistant depression, and later for depression with acute suicidal thoughts.