R-Ketamine vs. S-Ketamine: What's the Difference and Why It Matters

Two Molecules, Different Properties

The word "ketamine" actually refers to a family of molecules. Understanding the distinction between its two forms — and the racemic mixture that combines them — can help you make sense of your treatment options.

The Molecular Basis

Ketamine exists as two mirror-image molecules called enantiomers: R-ketamine (arketamine) and S-ketamine (esketamine). Think of them like your left and right hands — nearly identical, yet not interchangeable.

Both interact with brain receptors governing mood, perception, and pain, but through subtly different mechanisms.

How They Differ

Potency and Speed

S-ketamine binds more strongly to NMDA receptors, producing faster anesthetic effects and more pronounced dissociative experiences. This property led to its FDA approval as Spravato for treatment-resistant depression.

R-ketamine is less immediately potent but shows potential for producing more sustained antidepressant benefits — possibly at lower doses.

Side Effects

S-ketamine's stronger NMDA binding often triggers more noticeable dissociation — that "detached or floaty" feeling during sessions. R-ketamine may produce fewer dissociative and psychotropic effects, though research is ongoing.

Duration of Benefit

Preliminary studies suggest R-ketamine's antidepressant properties persist longer than S-ketamine's. This makes it appealing for patients who prefer fewer treatment sessions.

Mechanism of Action

S-ketamine primarily operates through NMDA receptor blockade, increasing glutamate and promoting synaptic growth. R-ketamine appears to enhance neuroplasticity through gentler, more sustained pathways — potentially yielding balanced mood improvements with less cognitive disruption.

What's Available Today

FDA-Approved: S-ketamine (Spravato) is the only FDA-approved enantiomer. It's administered as a nasal spray under medical supervision.

Racemic ketamine: Most IV and oral ketamine therapies — including what we use at Discreet Ketamine — employ racemic formulations containing both R and S forms in equal measure. This balanced mixture has decades of safe clinical use and remains the standard for off-label mood and pain treatment.

R-ketamine: Pure R-ketamine remains investigational. Early findings are encouraging, but it's not yet available for clinical use.

What This Means for Your Treatment

At Discreet Ketamine, we use racemic ketamine, which gives you the therapeutic benefits of both enantiomers. The R component may contribute to longer-lasting mood improvement, while the S component provides the more immediate antidepressant effect.

As research progresses, pure R-ketamine formulations may eventually offer an option for patients who want milder experiences or longer-lasting results. For now, racemic ketamine remains the most well-established and evidence-supported approach.

For a broader view of treatment options, see our guides to IV vs. sublingual ketamine and all the ways ketamine can be given.