[derefr]

> I would speculate that LSD turns on System 2 where normally my System 1 brain would give me an immediate response.

As far as I've read, LSD is, surprisingly, just a serotonin agonist, similar to anti-depressants or MDMA. (Technically, it's a non-selective serotonin agonist, and it does this by reversing the chemical reactions that take serotonin apart, to basically "un-use-up" serotonin you've already spent--which might explain its differing experiential effects--but in the end it still means "more serotonin in the brain.")

Now, the two things serotonin has been heavily implicated for in neurology, are pleasure (though not reward; that's dopamine), and neurogenesis: serotonin is basically released when something "feels good" in a sensual way--something looks aesthetically pleasing, something tastes delicious, etc.--as a signal to the rest of your brain to backtrack to what caused this stimulus to happen, and build up the neurons involved. Basically, if I find some tasty berries while foraging, reinforce the memory of the walk I took to get to the berries. [This effect can be harnessed: consume a bit of some fat-saturated food right after you study something, if you want to remember it better.]

But LSD, MDMA, and other drugs that stimulate serotonin release, can have psychedelic effects well beyond what you'd expect from "remembering things better." This is because the reaction to serotonin, neurogenesis, goes way beyond sensible memory formation. It takes any spikes in electrochemical activity that are going on in the brain at the time, and says "that: build up the synapse for that." And, of course, neurons have an underlying level of noise, that usually gets buried under actual cognition--so, when you turn the "gain" up on what "becomes brain cells", suddenly you start forming 'concepts' for ideas that are made of nothing at all--the feeling of seeing shared properties between things that have none. Which would indeed, likely, be best described as "a trip."

Of course, this also informs the other thing people--especially those in creative fields--say about LSD: that it's a life-altering experience, quite foundational for later productive work. This is basically because pushing up the "noise floor," if you have a lot of potential ideas lurking just below the surface as potential connections you haven't made between concepts, ready to be exploited--they'll get wired together by the non-selective flood of serotonin too. But, unlike the nodes for "the purpleness of music" or what-have-you, these nodes will actually self-reinforce once created--that is, they're useful to have, so you'll keep using them--so they'll stick around, whereas the other synapses will just get their reactivity scaled back down when it turns out how purple a song is doesn't have any causal impact on anything else. :)

[draakon]

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

[derefr]

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...

[draakon]

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.

[gwern]

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

[nathan_f77]

That was incredibly insightful, thanks very much for posting!

[coldtea]

>I happen to be a software engineer and try to apply my knowledge of "machines" to the psychedelic experience. While I don't believe in anything supernatural, I do think that there might be a chance that psychedelics, especially LSD, help your consciousness tap into some deeper abstractions of the human mind, maybe even the universe. Let me explain that insane claim as best I can

I don't find this claim insane at all.

A substance that changes how the mind functions (at whatever level) is also likely to help one see abstractions, connections and solutions that he normally bypasses.

Heck, even the morning coffee helps a lot of people to tackle some problems they would otherwise have difficulty in tackling.

[virtualwhys]

Thanks, succinct explanation of the tripping mind. Have always felt there was some level of distortion in the trips I've taken, as if something were being created from nothing.

Then again, that is the appeal of the trip, the mundane takes on a life of its own and becomes something else entirely -- the oh, now-I-get-it-what-a-fool-I've-been-experience, it's been here all along!

Later, returning to work, relationships, etc., the trip becomes a memory, some far more pronounced than others, but a memory nonetheless.

Life is a moving stream, nothing to hold on to here.

[nanidin]

I found the series of videos by David Nichols to be very informative of what current science actually understands about psychedelic drugs: http://www.youtube.com/watch?v=L_ud3NkZGmI

[im3w1l]

Sanity check for your argument: How many synapses are formed during the typical trip?