The History of Ketamine: From
Operating Rooms to Mental Health Care

Ketamine’s use in mental health may feel relatively new, but its medical history spans more than half a century.

Long before it was studied for depression or PTSD, ketamine was widely used as an anesthetic in operating rooms and emergency care worldwide.

Early Development and Medical Use

Ketamine was developed in the 1960s as a safer alternative to existing anesthetic agents. It was designed to provide effective sedation and pain control while preserving breathing and cardiovascular stability—an important advantage in surgical and emergency medicine.

Because of these properties, ketamine became widely used in:

Operating rooms
Emergency departments
Trauma and battlefield medicine

Its long-standing role in global medicine is reflected by its inclusion on the World Health Organization Medicines List, underscoring its established safety profile when used appropriately by trained clinicians.

An Unexpected Observation

As ketamine was used more broadly, clinicians began noticing an unexpected pattern. Some patients who received ketamine for anesthesia or pain management reported short-term improvements in mood following treatment.

Although these early observations were anecdotal, they were consistent enough to raise important scientific questions about whether ketamine might directly affect brain systems involved in mood and depression.

The First Modern Clinical Trial in Depression

In 2000, researchers at Yale School of Medicine conducted the first widely recognized randomized, placebo-controlled clinical trial examining ketamine’s antidepressant effects. Led by psychiatrist John H. Krystal, MD, the study demonstrated that a single low-dose intravenous infusion of ketamine produced rapid and significant reductions in depressive symptoms compared with placebo in patients with depression.

This landmark finding challenged the long-held belief that antidepressant treatments must take weeks to produce meaningful effects.

Expansion of Ketamine Research in Mental Health

Following the Yale study, further research—much of it supported by organizations such as the National Institutes of Health—replicated and expanded upon these findings, particularly in individuals with treatment-resistant depression.

Subsequent studies helped clarify:

Appropriate low-dose protocols for psychiatric use
Safety and monitoring standards
Which patient populations may benefit most

Over time, ketamine transitioned from an experimental research subject into a clinically used treatment option in specialized, medically supervised settings.

Ketamine in Modern Mental Health Care

Today, ketamine is used in structured treatment programs for carefully selected patients with depression and related conditions. While research continues to refine best practices, ketamine is no longer considered experimental when delivered appropriately and under medical supervision.

Its evolution—from operating rooms to mental health clinics—reflects a broader shift in psychiatry toward understanding depression as a condition involving disrupted brain connectivity and impaired neural flexibility, rather than solely a chemical imbalance.

Understanding ketamine’s medical history provides important context for its current use in psychiatry. For a clinical overview, you may find it helpful to review what ketamine therapy is and how it is used today, as well as a more detailed explanation of how ketamine works in the brain and affects neural connectivity.