Those points seemed already covered in the article, but somehow it must have been unclear.
First of all, it's unlikely to ever have ketamine as a first-line treatment for a depression. Probably more somewhere near electroconvulsive therapy. ECT also has adverse effects which can't be considered as minor (e.g. severe memory loss). However, at the same time it's recognized as a life-saver for certain population of patients.
As I have understood from this research and previous ones, it's hoped that the effect of ketamine would be long-lasting: at least up to months. Not so-called daily anti-depressant pill. The adverse effects of ECT would also be more severe if it would be administered on a daily basis. As it was mentioned, some patients relapsed within days, some were free from depression for up to three months.
According to animal research[1], it's prolonged not acute ketamine use that has shown signs of renal and bladder damage. In a review of ketamine-induced vesicopathy[2] it's also noted that 'Very little is known regarding the pathogenesis of its effects on the urinary tract.' I'm not claiming that it doesn't cause any damage, but that it needs more research and currently there's no indication of "renal havoc" after few doses.
In light of this, I can't even imagine how someone could call possibility of using ketamine for treatment of depression not viable. However, it may be because I know how disabling severe or even moderate depression is and how much damage it causes to person's life.
Each person reacts very differently to anti-depressants and there's large amount of people with treatment resistant depression. It's not like there's silver bullet and because of that we need as many as possible different treatment methods. Depression is life-threatening condition and thus all of those methods can't (and don't need to) be 100% safe. A lot of approved drugs have serious side-effects. Basically it's all about assessing the benefit:risk ratio of a drug. It's not rational to cross any treatment out, just because it may have side-effects. Especially if there's not reasonable amount research done - like with ketamine.
When we have more data, then it may show that certain population would need additional doses of ketamine after 1-3 months and the damage to organs is minor or non-existent in such case. Or it may show something else. It's just unthinkable to call it as "not viable" option, yet.
[1] Yeung, LY, Rudd JA, Lam WP, Mak YT, Yew DT. (2009) Mice are prone to kidney pathology after prolonged ketamine addiction. Toxicol Lett. 2009 Dec 15;191(2-3):275-8. doi: 10.1016/j.toxlet.2009.09.006. Epub 2009 Sep 17.
[2] Middela, S., Pearce, I. (2010) Ketamine-induced vesicopathy: a literature review. Int J Clin Pract. 2011 Jan;65(1):27-30. doi: 10.1111/j.1742-1241.2010.02502.x.
Thank you for this very interesting post, but I would like to point out a few things.
Most currently used anti-depressants are serotonin (some also norepinephrine and/or dopamine) reuptake inhibitors, not agonists. Tetracyclic antidepressants even act as antagonist (inverse agonists). Buspirone (more an anti-anxiety than AD medication) functions as a serotonin receptor partial agonist, but that is selective (5-HT1A) and I have never heard that it has any psychedelic value.
I would say there's a way more than just "more serotonin in the brain". That suggestion is even VERY DANGEROUS: too much serotonin means serotonin syndrome, which is potentially fatal condition. It may cause hallucinations, but rarely pleasurable ones and they are accompanied by various unpleasant symptoms such as nausea, sweating, tremor and eventually death. So, please don't try to abuse SSRI/SNRI anti-depressants. Few other AD-s have recreational value (for example tianeptine), but not for psychedelic experiences.
Right--I probably shouldn't have even mentioned anti-depressants; X-monoamine reuptake inhibitors don't have much at all to do with X-monoamine agonists in terms of effect.[1] I was mostly just trying to connect the discussion to something people would more commonly have actual experience with.
So, to reinforce the parent: serotonin syndrome is very dangerous for precisely that reason of "neurological gain" mentioned above--eventually when you turn gain up enough, you get clipping[2], and then you don't have a signal any more, you have a seizure. Surprisingly, it's very hard to do this with LSD--probably because of its differing pharmacodynamics from regular serotonin agonists--but it's a real risk of pretty much any other drug that affects serotonin at all, either in overdose, or in combination with other drugs, even ones you might not expect (the nicotine in cigarettes is an MAOI!)
But anyway, it's really a shame that we aren't each (legally) given the neurological equivalent of a "chemistry set" at some point in our lives, to adjust all the knobs on our own brains and learn the effects. Knowing what serotonin, dopamine, GABA, acetylcholine, etc. are in a clinical sense is one thing; but intuitively understanding that a feeling you're experiencing is the way it feels from the inside[3] when some monoamine or another happens to be at a certain level of concentration in your brain at the moment, is quite another.
[1] Though you'd be surprised what things are, in fact, reuptake inhibitors (what you classically think of as "therapeutic drugs") instead of agonists (what you clasically think of as "stimulants.") Cocaine, for example, is just a triple (serotonin, dopamine, and norepinephrine) reuptake inhibitor; basically, ADD medication + an SNRI anti-depressant. In another society without our history of race-discrimination-related drug bans, Coca Cola (the original stuff) might be the office-worker's morning stimulant of choice instead of coffee. :)
The lossless 60 fps high definition video capture is currently unavailable (traffic limit). Any mirrors (or torrent would probably be a pretty good idea)?
YouTube 1080p version seems to have pretty terrible quality.
I feel stupid, but just don't get it. Why should I unfriend them for liking some rock band?