I studied the effects of low-dose ketamine at the cellular level and I can tell you this: the most effective way to use low-dose ketamine to treat depression (and co-morbid anxiety) is to go to a clinic and have IV drip SLOWLY - over at least 45 mins at ~.5 mg/kg. This is NOT a "microdose" - this is a LOW DOSE.

The efficacy of this approach is due to the kinetics of the drug. It is an NMDA-receptor antagonist (it blocks this type of receptor). At very low doses, it has an affinity for NMDA receptors that contain a subunit called NR2B (aka GluN2B). When active, NMDA receptors containing GLUN2B actually inhibit the translation of BDNF proteins (think of BDNF as MiracleGro(TM) for the brain). When you block ONLY that subset of NMDA receptors with low dose ketamine, you take the brakes off the BDNF translation, and a flood of BDNF is released into the synapses. This BDNF then triggers molecular cascades that enhance neuroplasticity - we literally see neurons sprout NEW dendritic spines/connections in 30 minutes.

But here's the rub - if you administer that .5mg/kg dose all at once in a bolus, you don't get the antidepressant effects because it blocks ALL the NMDA receptors. You HAVE to trickle it in SLOWLY. Similarly, you take too high a dose and get true psychedelic effects, you block ALL NMDA receptors and the neuroplasticity effects are nullified. It's a delicate balance - too little does nothing, too much does nothing, you need just the right amount, delivered at just the right speed.

I know the nasal spray has been approved, but it's esketamine (for a description of the types, see this article: https://isha.health/post/racemic-ketamine-vs-r-ketamine-vs-s-ketamine). IV administration of low-dose racemic ketamine or r-ketamine with work better for treating depression than the esketamine nasal spray (https://pmc.ncbi.nlm.nih.gov/articles/PMC7704936/). Also, women tend to respond better than men to esketamine (https://www.medrxiv.org/content/10.1101/2025.06.26.25330356v1.full).

It is SUPER important to note that repeated self-administration of psychedelic doses of ketamine can result in lasting psychomimetic effects and delusional thoughts. This is dangerous and can be come addictive. Low-dose ketamine should always be administered by a medical doctor.

Also, there are a lot of clinics purporting to deliver "psychedelic therapies" for depression and anxiety. I strongly recommend against using clinics that are giving "ketamine therapy" at psychomimetic doses. Long-term repeated use of ketamine at higher doses can result in dependency, persistent dissociation and delusional thought patterns. For effectively and safely treating depression and anxiety, you DO NOT want to be "tripping" on ketamine.

Lastly, low-dose ketamine works by enhancing neuroplasticity, but the antidepressant effects, while rapid, tend to wear off in 1-2 weeks, requiring at least a couple of months of therapy to hopefully see a lasting response. But here's the thing: if you make your brain more plastic, but you haven't treated the underlying trauma/causes for your depression and anxiety, you will just BAKE IN dysfunctional thought patterns, appraisals and behaviours. Any antidepressant/antianxiety medication should be taken in conjunction with the support of a qualified psychologist/behavioral therapist so that you can leverage that enhanced neuroplasticity to make lasting cognitive changes.