Navigating the Ketamine Landscape: History, Uses, and Myths

PA Mindset
Oct 28
3 min read

Welcome to an exploration of the evolving world of ketamine therapy. In this episode, we unpack ketamine’s fascinating journey—from its origins in the 1960s to its role today as a rapid-acting antidepressant and a catalyst for transformation in psychiatry.

From Battlefield to Breakthrough: Ketamine’s Origin Story

Ketamine’s story begins in the 1960s—an era of bold medical discovery and psychedelic exploration. Developed by Calvin Stevens, ketamine was first used as an anesthetic and gained prominence during the Vietnam War for its safety and rapid action on the battlefield. Later, it became a staple in veterinary medicine.

But as its dissociative effects became known, ketamine shifted into the public sphere—earning street names like “Special K” and “Vitamin K.” Its reputation as a party drug overshadowed its legitimate medical value for decades, even as researchers began uncovering its psychiatric potential.

Clinical Revival: From Party Drug to Psychiatric Game Changer

Today, ketamine has re-emerged as a powerful tool in the treatment of treatment-resistant depression, PTSD, and chronic pain. The FDA approval of Spravato® (esketamine) in 2019 marked a turning point, providing a regulated, evidence-based framework for use in mental health care.

Ketamine vs. Esketamine: What’s the Difference?

Racemic Ketamine: Contains both R- and S- isomers.
Esketamine (Spravato®): Contains only the S- isomer, offering higher NMDA receptor affinity and greater potency with potentially fewer dissociative effects.

While both forms modulate glutamate and enhance BDNF (Brain-Derived Neurotrophic Factor)—a “fertilizer” for neuronal growth—their dosing routes, onset, and bioavailability differ. Esketamine is administered intranasally (bioavailability 25–50%), whereas racemic ketamine can be given IV or IM, with near-complete absorption.

Ketamine Myths: What the Science Really Says

In our conversation, we tackled several common misconceptions:

“Ketamine is just a party drug.”➤ False. Ketamine’s medical applications are extensive and growing, particularly for resistant mood disorders.
“It works the same as SSRIs.”➤ False. Ketamine targets glutamatergic pathways, offering rapid symptom relief compared to serotonin-based mechanisms.
“Ketamine therapy is unregulated.”➤ Partially true. Racemic ketamine infusions are less regulated, while Spravato® is strictly administered in REMS-certified treatment centers.
“Ketamine causes brain damage.”➤ False. When medically supervised, ketamine shows no neurotoxicity and may promote neuroplasticity.
“Ketamine is addictive.”➤ Misuse risk exists, but structured therapy and clinical protocols minimize dependence potential.

A Catalyst, Not a Cure: Integrating Psychotherapy

As we emphasize in the episode, ketamine is not a cure—it’s a catalyst. Medication opens the door; psychotherapy walks the patient through it. When paired with therapeutic integration, ketamine can enhance emotional openness, neuroplasticity, and long-term treatment response.

The neuroplastic window—lasting hours to days—creates an opportunity for deeper cognitive and emotional processing. Structured approaches involving preparation, guided sessions, and post-treatment integration can reduce relapse rates and sustain improvement.

Looking Ahead: The Future of Ketamine in Psychiatry

Research on esketamine monotherapy, combination treatments, and long-term outcomes continues to evolve. While it’s still early since Spravato’s approval, data show promise in expanding ketamine’s role in psychiatry and beyond.

For PAs and clinicians seeking guidance on integrating ketamine into practice, visit the American Society of Ketamine Physicians, Psychotherapists & Practitioners (ASKP3) for resources, certifications, and clinical directories.

Continue the Conversation

Stay curious. Stay informed. And keep exploring the intersections of science, empathy, and innovation in mental health care.

🎧 Listen to the full episode:👉 “Ketamine: From Battlefield Anesthesia to Breakthrough Antidepressant” — streaming on Spotify, Apple Podcasts, YouTube, and Podbean.