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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.

https://en.wikipedia.org/wiki/Anti-depressants

https://en.wikipedia.org/wiki/Tricyclic_antidepressant

https://en.wikipedia.org/wiki/Serotonin_syndrome



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. :)

[2] http://en.wikipedia.org/wiki/Clipping_(audio)

[3] http://lesswrong.com/lw/no/how_an_algorithm_feels_from_insid...


Thanks, you have interesting points.

To others who are interested in psychoactive drugs I would like to suggest following book (you are probably already familiar with it):

A Primer of Drug Action by Robert Julien ( http://www.amazon.com/Primer-Drug-Action-Robert-Julien/dp/14... )

It contains concise and objective information about various psychoactive substances, their effects and mechanisms of action.


My understanding was that nicotine is not a MAOI; but tobacco has other MAOIs in it: http://www.gwern.net/Nicotine#fn2




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