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

Ketamine has quickly become one of the most promising treatments for depression, anxiety, and chronic pain when other approaches fall short. But not all ketamine is the same. If you’ve researched treatment options, you’ve probably seen terms like “S-ketamine,” “R-ketamine,” or “racemic ketamine.”

Understanding these differences helps you make informed choices about your care. Here’s what you should know.

The Science Behind R and S Ketamine

Ketamine actually comes in two mirror-image molecules — called enantiomers — known as R-ketamine (arketamine) and S-ketamine (esketamine).

Think of them like your left and right hands: nearly identical, yet not interchangeable. Both versions affect receptors in the brain that regulate mood, perception, and pain — but they do so in slightly different ways.

• S-Ketamine binds more strongly to NMDA receptors, producing faster anesthetic and dissociative effects.

• R-Ketamine has a weaker NMDA response but may act on other pathways related to mood and neuroplasticity, such as BDNF and mTOR signaling.

In clinical use, many formulations, including IV and sublingual ketamine — are “racemic,” meaning they contain a 50/50 blend of both R and S forms.

Clinical Differences Between R- and S-Ketamine

1. Potency and Onset

S-Ketamine is more potent as an anesthetic and tends to act faster. This is part of why Spravato® (esketamine), the intranasal form of S-ketamine, received FDA approval for treatment-resistant depression.
R-Ketamine, while less potent in that traditional sense, shows early evidence of producing longer-lasting antidepressant benefits.

2. Side Effects

Because S-Ketamine binds more strongly to NMDA receptors, it often leads to more noticeable dissociation (feeling detached or “floaty”) during a session.
R-Ketamine may cause less dissociation and fewer psychotropic side effects, though this is still under study.

3. Duration of Benefit

Some animal and early human studies suggest R-Ketamine’s antidepressant effects may last longer than S-Ketamine’s, even at lower doses.
This could one day make R-Ketamine an appealing option for patients who prefer fewer treatments or milder experiences, though research is ongoing.

4. Mechanism and Mood Impact

S-Ketamine primarily works through NMDA receptor blockade, increasing glutamate and promoting synaptic growth.
R-Ketamine appears to influence different pathways that may enhance neuroplasticity in a gentler, more sustained way. This could mean more balanced mood improvements with potentially less cognitive disruption.

What’s Available Right Now

• FDA-Approved Option:
  S-Ketamine is currently the only enantiomer approved by the FDA, marketed as Spravato®, a nasal spray for adults with treatment-resistant depression.
  Because of its potential for dissociation and blood pressure changes, it must be administered under medical supervision in a certified setting.

• Racemic Ketamine (R/S mixture):
  Most IV and oral ketamine treatments, including those used at Discreet Ketamine, are racemic, containing both R and S forms in equal parts.
  This balanced mixture has been used safely for decades and remains the gold standard in off-label ketamine therapy for mood and pain disorders.

• R-Ketamine:
  Pure R-Ketamine is not yet FDA-approved and remains in the research phase. However, early findings are promising and may shape the next generation of ketamine-based treatments.

What This Means for Patients

At Discreet Ketamine, we currently use racemic ketamine, which offers the combined therapeutic benefits of both R and S forms. Our approach focuses on safety, comfort, and privacy, ensuring that every treatment is delivered in a calm, safe environment, whether at home or in a clinic.

As research evolves, newer formulations such as R-Ketamine may offer additional options for patients seeking gentler or longer-lasting results. Until then, racemic ketamine remains a highly effective and evidence-based therapy for many conditions.