Summary
Esketamine is the S-enantiomer of ketamine and is FDA-approved for treatment-resistant depression when administered intranasally under medical supervision. It is approximately 4 times more potent at NMDA receptors than the R-enantiomer and approximately 2 times more potent than racemic ketamine. Side effects include dissociation, dizziness, sedation, increased blood pressure, and nausea. Contraindicated in individuals with aneurysmal vascular disease, uncontrolled hypertension, or history of psychosis. Available only through REMS program (Spravato REMS) in the US.
Dose Information
Light
Common
Strong
Heavy
Onset, Duration & After-effects
| ROA | Onset | Comeup | Peak | Offset | After Effects |
|---|---|---|---|---|---|
| Intranasal | 5-15 min | 5-15 min | 20-60 min | 1-2 hrs | 2-24 hrs |
| Intravenous | 1-5 min | 2-5 min | 10-30 min | 45-90 min | 2-24 hrs |
| Intramuscular | 2-10 min | 5-15 min | 30-60 min | 1-2 hrs | 2-24 hrs |
Tolerance
Build-up
develops with repeated use over days to weeks
Reset
2–4 weeks for noticeable reduction
Effects
Positive
- Pain relief
- Analgesia
- Stimulation
Negative
- Increased blood pressure
- Nausea
- Vertigo
- Insomnia
- Headache
- Sedation
- Physical disconnection
Positive
- Cognitive euphoria
- Conceptual thinking
- Immersion enhancement
- Depression reduction
Negative
- Depersonalization
- Derealization
- Motor control loss
- Memory suppression
- Cognitive disconnection
- Dizziness
- Anxiety
- Dissociation
- Time distortion
Positive
- Physical enhancement
Negative
- Spatial disorientation
- Derealization
- Light sensitivity
- Disinhibition
- Appetite suppression
- Visual distortions
- Visual disconnection
- Dulled perception
- Metallic taste