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I know that 5-HT2A partial agonism is the key mechanism of action of serotonergic psychedelics but I also know that some research (e.g. the selective (no activity on any other known receptor sites) 5-HT2A inverse agonist/antagonist eplivanserin was being investigated as a sedative) says that central blockade of the 5-HT2A receptors induces sedation which is in opposition to the effect of 5-HT2A partial agonists.

I have a partial answer to my question. I heard from LSD users that they find it regularly causes sleeplessness for the duration of its effects, which is likely due to stimulant/wakefulness-promoting (eurogenic) effects. Albeit just because it is true for one serotonergic psychedelic doesn't necessarily mean it is true for all serotonergic psychedelics. Especially since LSD affects a wide range of serotonin and other receptor subtypes.

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  • $\begingroup$ You have some great questions that I wish I knew the answers to. Just a suggestion, you might want to see if your library can get Goodman and Gilman's for you. I don't know if the answer to this would be in there, but it is definitely the "go-to" reference book for pharmacology. $\endgroup$
    – jonsca
    Jan 31, 2013 at 5:40

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I think you'll like this article. It's on monoamine release / reuptake inhibition for a host of different psychedelic and empathogenic drugs.

This wakefulness inducing effect you describe for LSD is widely reported for all common 5-HT2 mediated psychedelics.

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