Ketamine (Ketamine (and esketamine))
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.
Community reviews of Ketamine
- tracker968 rated it 5/5 - Fast lift, but the fog after was real: Ketamine was the first thing that actually pulled me out of that flat, gray headspace in about 6 weeks. I’m on the East Coast, training clients all day, so I needed my brain back fast. The downside for me was a weird spaced-out feeling and some nausea after sessions, which honestly bugged me 🥗
- nomad694 rated it 4/5 - Fast reset, but I still prefer therapy days: I tried ketamine for about 12 weeks after a brutal stretch where my mood was dragging and my running had started to feel like a chore, which is deadly for me because training is usually my headspace. It did lift the fog quickly for me, faster than the SSRI I had been on before, but the sharpest effect was short lived and I felt a bit floaty after sessions. I actually preferred structured psychotherapy overall, though ketamine gave me a useful jump start?
- scientist_maya rated it 1/5 - Floaty, foggy, and not much else: I tried ketamine for about 6 weeks after a rough stretch where my mood was flat and my brain felt stuck in molasses. I work long pharmacy shifts on the East Coast, so I was hoping for something that would at least help me reset. For me, it mostly felt like being weirdly detached and then tired after. The relief was brief, and I didnt get the clear lift I was hoping for. 1 star.
- practical_runs rated it 5/5 - Helped me get my head back for coaching and training: As a 56-year-old CrossFit coach in the Netherlands, I tried ketamine because I was stuck in a very flat patch and my usual routines were not cutting through it. For about 8 weeks, it seemed to give me a reset that made work feel less heavy and my own training feel more normal again. I could focus better with clients, and I was not dragging that grey mood into the gym every day. The effect was not subtle for me, though of course this is just my own experience. It fit my life better than I expected, because I could still coach, sleep, and keep my week structured.
- zoe_rows rated it 5/5 - Ketamine gave me a hard reset when I was stuck: I ran ketamine for about 4 months because my brain felt jammed up, like I could not get out of a rut even doing all the normal East Coast overachiever stuff, work, training, sleep, repeat. For me, it kicked in fast and that was the whole point. The fog and that heavy, trapped feeling eased up more than anything else had. I was a little weirded out at first, to be fair, but the change was real enough that I kept going. Just my own experience, but I came out of it feeling more like myself again.
- wes149 rated it 4/5 - Quieted the spiral fast enough for me to breathe: The biggest thing for me was how fast it seemed to take the edge off that heavy, wired-down depression. I’m a retired firefighter in the Midwest, so I’ve seen my share of rough patches. After about 3 months, I felt more usable again, though the after-session fog was a little annoying...
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Research and educational reference only. Not medical advice.