There is something i keep hearing from internet people that i cant really get/doesnt make much sense to me.
And thats the reason why ssri blunt lsd experience, people often say that the reason of such an effect is that ssri increase synaptic concentration of serotonin which in turn competes with LSD at 5HT2A receptor, making LSD bind less at such receptor and so decreasing its effects.
If serotonin competes with LSD at 5HT2A receptor, by common sense, it wouldnt decrease lsd effect because the 5HT2A would still be activated by serotonin!!!!
So,
the LSD blunting effect (of long/intermediate term use) of SSRI comes from receptor downregulation/desensitization caused by high conc of serotonine or,
LSD and serotonin have different activity/efficacy at 5HT2A, more precisely serotonin'd have to behave more like a partial agonist to that receptor in comparison with LSD which would have to be more full agonist-like at said receptor, however the fact is that i have often read that LSD is a PARTIAL AGONIST at 5HT2A and unless serotonin itself is a partial agonist at the 2A i cant see why LSD displacement by serotonin would result in decreased effects, I would really like to see values of Intrinsic Activity of serotonin and LSD at 5HT2A to understand better their relative efficacy.
Maybe 5HT2A receptor is so complex that doesnt follow the linear pattern of agonist/partial agonist/ antagonist, so maybe LSD and serotonin activate that receptor in radically different ways thus explaining competition.
Another possible explanation of SSRI blunting of LSD could be that serotonin activity at receptors that aren't target of LSD could simply counterbalance the overall psychedelic experience.
So, all my discourse about direct competition won't make sense if before we can't rule out the effect of receptor desensitization/downregulation on SSRI blunting of LSD,
a suggestion would be to investigate if even a non-chronic, single coadministration, of SSRI with LSD will decrease the psychedelic effects.
If it doesnt decrease, then the said effect is almost surely due to desensitization/downregulation, which occurs only (maybe) with cronic SSRI use,
but if psychedelic effect does indeed decrease it could be because of direct comperition OR more general unspecific effects.
Long story short, how to discriminate between these two last possibilities? anyone with LSD and serotonin Intrinsic Activity values on 5HT2A???
Meditate people, meditate!!!