Is there a maximum effective dose of psilocybin?

August 16, 2015 3:19 PM

I have heard and read that psychedelics like LSD and shrooms act on serotonin receptors and that once those receptors fill up (either with actual serotonin or antagonists) no additional effect will be felt from taking a higher dose. I would really like to find actual academic references about this, but all I'm seeing is casual comments on message boards, backed up with nothing. Unfortunately, my Google Fu is failing me here and it's driving me crazy.

Anyone have any references to scientific studies, or even just credible scientific explanations from reputable sources on this topic?

posted by mysterious_stranger to Science & Nature (8 answers total)

I don't have any reference but there is a maximum survivable dose of psilocybin, just like any substance, and that implies that at a certain point (although it's a pretty large quantity from what I can deduce), it's going to start making you feel pretty bad.
posted by treehorn+bunny at 3:58 PM on August 16, 2015

following on from the above, the LD50 (amount that has a 50% chance of killing you, afaik) for psilocybin is given on the wikipedia page, but only for mice, rats and rabbits.
posted by andrewcooke at 4:12 PM on August 16, 2015

Hi,

Thanks for the feedback but maximum survivable dose is not actually what I am interested in.

Again, I'm looking for any info on the concept that once your serotonin receptors are occupied, taking additional substance will have no additional effect. Any info on this-even just whether that is true or not-is appreciated.
posted by mysterious_stranger at 4:50 PM on August 16, 2015

i hear it also causes irritability and repetitive behaviour...

if you read Recent advances in the neuropsychopharmacology of serotonergic hallucinogens (abstract) you'll see in the summary (p44):

It appears that 5-HT2A activation is a common characteristic of serotonergic hallucinogens and is responsible for mediating their shared effects, but this does not eliminate the possibility that other receptors may play an ancillary role.

(it's worth reading more - it gets quite poetic).

in other words - they don't know how it works. given that, how can they possibly make a prediction like you are seeking?
posted by andrewcooke at 5:42 PM on August 16, 2015

Erowid.org may have answers, but they'll tend to be anecdotal. Still, given the difficulty in setting up experiments in humans, Erowid's forums often contain real gems of warnings and genuine side effects that are not really available elsewhere (along with lots of amateur "trip" diaries).

Try asking there. :)
posted by IAmBroom at 6:40 PM on August 16, 2015

I think you're thinking of agonism

You're assuming though that having all of your serotonin receptors maximally stimulated is compatible with life, and that is not the case.
posted by tinkletown at 4:22 AM on August 17, 2015

So yes, there is likely to be a theoretical maximum dose above which there would be no further effect but no, nobody can tell you what that is for humans because it's more than the toxic dose.

In terms of extrapolating from in vitro experiments, I doubt it's been done. It's the kind of thing people might have looked at in the 60s but the science wasn't advanced enough (most of the 5HT receptors were first cloned in the 80s and 90s). These days it is just too difficult to work with hallucinogens due to all the paperwork.

This gives toxicity info, but not receptor saturation (because I don't think it's known). This and this are behind a paywall, but were the best I could find on pubmed (I have institutional access, they don't cover individual receptor saturation just dose response curves and metabolism, understandably because that's the most clinically relevant info). I just don't think it's been looked at, because what's the point if it's higher than the toxic dose?
posted by tinkletown at 5:47 AM on August 17, 2015

I can't give you scientific data, but I can tell you from personal experience that the level at which the effect of psilocybin stops increasing is well above the level at which you would want it to stop increasing.

More specifically, about 20 years ago I ate too many mushrooms, lost contact with reality, fell down the stairs, pissed my pants, couldn't figure out if I was bored or terrified, drove my truck down the road and ran it into my neighbour's woodpile (fortunately not my neighbour), then became convinced that reality was based on attitude and belief, and that I could be anywhere or do anything if I believed it.

My current belief is that I ate more mushrooms than I should have.
posted by crazylegs at 7:32 AM on August 17, 2015