[mruts]

What biological mechanism would make this the case? Are you saying it has to do with bio-availability? Half-life? Onset? Duration?

What about IM? What about rectal administration? How about sublingual? Are there any papers suggesting that IV is somehow quantitatively different from the aforementioned methods?

My personal experience is that IM, IV, and snorted all made me feel better for maybe a period of 2 weeks. I wasn't necessarily doing a "clinical" dose, whatever that means (maybe 25-75mg of IM or IV and 100-250mg snorted), but the anti-depressant effects all seemed comparable.

A drug crossing the blood-brain barrier is a drug crossing the blood-brain barrier. There should be no difference in administration if we are talking about weeks to months later.

[ketathrowaway]

The effectiveness of ketamine for depression is all about the state it puts your mind in. This is obvious because the drug itself has totally left your body shortly after administration, but the effects can last much longer. In this respect you can think of it as your mind actually healing itself, by being induced to by the ketamine, rather than the ketamine itself impacting your brain's structure. This is different from most conventional psychiatric medicine where the drugs need to build up and remain in your system over very long periods of time to be effective.

Optimizing the dose & duration to get your mind into that state, and for the right amount of time, makes a huge difference in how long the effects last. This is why I prefer using an actual doctor with ketamine depression treatment experience, because they have experience figuring out the right dose & duration for you.