Ketamine (Ketamine (and esketamine))

Category: Psychedelics. Status: Schedule III; esketamine FDA-approved for depression.

A dissociative anesthetic that, at lower doses, produces psychedelic-like effects and rapid relief from severe depression. The nasal-spray form esketamine is FDA-approved for treatment-resistant depression.

How it works

Blocks NMDA glutamate receptors, which is thought to quickly boost synaptic connections and lift mood. This is a different pathway from classic serotonin psychedelics.

Key facts

• Molecular weight: 237.73 g/mol
• Half-life: ~2-3 hours
• Bioavailability: IV, intramuscular, nasal, oral (varies)
• Storage: Clinical settings only.

Dosing overview

• Typical dose: Low sub-anesthetic doses for depression (clinic-administered)
• Frequency: A series of supervised sessions
• Duration: Acute effects last ~40-90 minutes
• Route: IV infusion, intramuscular, or nasal spray (esketamine)

Protocol notes

• In clinics it is given as an IV drip, a shot, or as the FDA-approved esketamine nasal spray, always under supervision.
• Sessions are short (under an hour) and repeated in a series over a few weeks for depression.
• Patients are monitored for blood pressure and dissociation and need a ride home.
• Recreational use (powder, "bumps") risks bladder damage and accidents and is much less controlled.

Reported benefits

• Rapid relief from treatment-resistant depression
• FDA-approved option (esketamine) exists
• Can reduce suicidal thoughts quickly
• Useful when other antidepressants fail

Possible side effects

• Dissociation and confusion
• Raised blood pressure
• Nausea
• Bladder problems with heavy long-term use
• Abuse potential

Research

• Esketamine nasal spray for treatment-resistant depression (2019): Pivotal trials supported FDA approval, showing reduced depression symptoms when added to an oral antidepressant.
• IV ketamine for depression and suicidal ideation (2018): Single infusions produced rapid, though often short-lived, reductions in depression and suicidal thoughts.

Compare Ketamine

• Ketamine vs MDMA
• Ketamine vs Psilocybin
• Ketamine vs LSD
• Ketamine vs Ibogaine
• Ketamine vs DMT
• Ketamine vs Ayahuasca

Community discussions about Ketamine

• PE 22-28 and the TREK-1 blockade angle, anyone seen any new preclinical movement - 4 comments
• PE 22-28 TREK-1 peptide for depression, anyone following the preclinical stuff - 4 comments
• Curious about low‑dose ketamine nasal spray experiences – what have you noticed? - 4 comments
• Does Ketamine Really Tune Your Sleep and Brain? 🔬 - 4 comments
• PE 22-28 TREK-1 blocker, anyone following the preclinical antidepressant angle - 3 comments
• Ask the community about Ketamine

Research and educational reference only. Not medical advice.